The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing rapidly worldwide due to the obesity epidemic. Advanced stages of the MAFLD, such as non-alcoholic steatohepatitis (NASH) with advanced fibrosis or cirrhosis are affecting global health. Extracellular vesicles (EVs) are released by all cell types and are important in cell-to-cell communication and maintaining homeostasis, but they also play a role in the pathogenesis of various diseases. EVs contain biological information such as lipids, proteins, messenger RNAs (mRNAs), small RNAs, and DNA, and they act on (distant) target cells. The cargo of EVs is dependent on the type and the state of the releasing cell. EVs have been proposed as biomarkers, prognostic, and even therapeutic agents, also in the context of liver diseases. This review aims to give an overview of the current knowledge on EVs in MAFLD, including the role and interaction of EVs with different cell types in the liver. Several aspects of EVs, including their origin, characteristics, cargo, and functions are reviewed. Moreover, the potential of EVs as targets for the treatment of MAFLD is discussed.
[Names] => Zongmei Wu ... Han Moshage [Doi] => 10.37349/edd.2022.00002 [Published] => July 13, 2022 [Viewed] => 2081 [Downloaded] => 61 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00002 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:4–20 [Recommend] => 0 [Keywords] => Extracellular vesicles, exosomes, metabolic dysfunction-associated fatty liver disease, non-alcoholic steatohepatitis, lipotoxicity, liver fibrosis, biomarkers, therapeutic application [DetailTitle] => [DetailUrl] => [Id] => 10052 [ris] => https://www.explorationpub.com/uploads/Article/A10052/eed496b59bf4cf2e7bd81ed633b155d1.ris [bib] => https://www.explorationpub.com/uploads/Article/A10052/c6e6758dfe12cedce1a0c60db342c459.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Wu Z, Xia M, Serna Salas S, Trillos-Almanza MC, Martinez Aguilar M, Arroyave-Ospina JC, et al. Extracellular vesicles in metabolic dysfunction associated fatty liver disease: mechanisms, diagnostic and therapeutic implications. Explor Dig Dis. 2022;1:4–20. https://doi.org/10.37349/edd.2022.00002 [Jindex] => 0 [CName] => HanMoshage, [CEmail] => a.j.moshage@umcg.nl, [Ris_Time] => 2022-07-13 07:29:46 [Bib_Time] => 2022-07-13 09:55:45 [KeysWordContens] => Extracellular vesicles in metabolic dysfunction associated fatty liver disease: mechanisms, diagnostic and therapeutic implications, Extracellular vesicles, exosomes, metabolic dysfunction-associated fatty liver disease, non-alcoholic steatohepatitis, lipotoxicity, liver fibrosis, biomarkers, therapeutic application, The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing rapidly worldwide due to the obesity epidemic. Advanced stages of the MAFLD, such as non-alcoholic steatohepatitis (NASH) with advanced fibrosis or cirrhosis are affecting global health. Extracellular vesicles (EVs) are released by all cell types and are important in cell-to-cell communication and maintaining homeostasis, but they also play a role in the pathogenesis of various diseases. EVs contain biological information such as lipids, proteins, messenger RNAs (mRNAs), small RNAs, and DNA, and they act on (distant) target cells. The cargo of EVs is dependent on the type and the state of the releasing cell. EVs have been proposed as biomarkers, prognostic, and even therapeutic agents, also in the context of liver diseases. This review aims to give an overview of the current knowledge on EVs in MAFLD, including the role and interaction of EVs with different cell types in the liver. Several aspects of EVs, including their origin, characteristics, cargo, and functions are reviewed. Moreover, the potential of EVs as targets for the treatment of MAFLD is discussed. ,Zongmei Wu ... Han Moshage [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [2] => Array ( [ArticleId] => 349 [Create_Time] => 2022-07-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202209/20220907025116.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10053/10053.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10053/10053.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10053/10053_cover.png [JournalsId] => 6 [Title] => Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma [Abstract] => Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic infla [AbstractComplete] =>Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic inflammation, leading to HCC progression. Moreover, fatty acids and cholesterol could display differential responses on immune cells inside the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs) represent one of the most critical leukocytes in the tumor microenvironment (TME) displaying pro-tumoral responses and one of the mainly cholesterol donors to cancer cells. Immunotherapy or cholesterol regulators, alone or combined, would represent an effective strategy for HCC treatment. Nonetheless, steatotic etiology from non-alcoholic fatty liver disease (NAFLD)-HCC tumors has been unexpectedly resulting in highly aggressive behavior.
[Names] => Alejandro Escobedo-Calvario ... María Concepción Gutiérrez-Ruíz [Doi] => 10.37349/edd.2022.00003 [Published] => July 29, 2022 [Viewed] => 2587 [Downloaded] => 76 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00003 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:21–39 [Recommend] => 0 [Keywords] => Hepatocellular carcinoma, cholesterol, inflammation, immune cells, macrophages [DetailTitle] => [DetailUrl] => [Id] => 10053 [ris] => https://www.explorationpub.com/uploads/Article/A10053/1c9a41d9de2dc132ad6c98fb637f416e.ris [bib] => https://www.explorationpub.com/uploads/Article/A10053/3f97eae19dd6186a476f42c8ec0b7574.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Escobedo-Calvario A, Chávez-Rodríguez L, Simoni-Nieves A, Souza-Arroyo V, Miranda-Labra RU, Gomez-Quiroz LE, et al. Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma. Explor Dig Dis. 2022;1:21–39. https://doi.org/10.37349/edd.2022.00003 [Jindex] => 0 [CName] => María ConcepciónGutiérrez-Ruíz, [CEmail] => mcgr@xanum.uam.mx, [Ris_Time] => 2022-07-25 08:26:48 [Bib_Time] => 2022-07-25 08:26:48 [KeysWordContens] => Tumor immune microenvironment modulation by cholesterol in hepatocellular carcinoma, Hepatocellular carcinoma, cholesterol, inflammation, immune cells, macrophages, Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic inflammation, leading to HCC progression. Moreover, fatty acids and cholesterol could display differential responses on immune cells inside the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs) represent one of the most critical leukocytes in the tumor microenvironment (TME) displaying pro-tumoral responses and one of the mainly cholesterol donors to cancer cells. Immunotherapy or cholesterol regulators, alone or combined, would represent an effective strategy for HCC treatment. Nonetheless, steatotic etiology from non-alcoholic fatty liver disease (NAFLD)-HCC tumors has been unexpectedly resulting in highly aggressive behavior. ,Alejandro Escobedo-Calvario ... María Concepción Gutiérrez-Ruíz [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [3] => Array ( [ArticleId] => 352 [Create_Time] => 2022-08-12 [zipUrl] => https://www.explorationpub.com/uploads/zip/202209/20220929042536.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10054/10054.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10054/10054.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10054/10054_cover.png [JournalsId] => 6 [Title] => The hepatocyte growth factor induces an anti-inflammatory and repairing response in the cholestasis-induced colon damage [Abstract] => Aim: Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such [AbstractComplete] =>Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such as the kidney, heart, and intestine, among others. One of the primary damage mechanisms is the generation of reactive oxygen species (ROS), which eventually leads to oxidative stress, impacting canalicular morphology and actin cytoskeleton changes that could worsen the problem. These characteristics are also observed in the kidney and intestine. The work focused on addressing the intestine effects of intrahepatic cholestasis induced by α-naphthyl isothiocyanate (ANIT) and the protective response of the hepatocyte growth factor (HGF).
The 10- to 12-week-old CD1 male mice were treated with ANIT and then treated or not with HGF; intestine damage was addressed by histology, immunohistochemistry (IHC) of specific markers, oxidative stress, and apoptosis.
Results show changes in the intestine histology, particularly the colon and ileum, induced by the cholestasis. HGF treatment restored the histology presentation and reverted the oxidative damage, clearly indicating a healing response. This observation was supported by an increment in anti-inflammatory macrophages (CD163+) in the HGF treatment.
The data prove that HGF induces a protective and repairing response in the intestine under cholestatic challenges.
Worldwide the number of individuals being overweight or obese has dramatically increased during the last decades, which is also associated with a similar dramatic increase of individuals afflicted with metabolic disorders like dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD). Genetic predisposition may account for some of the increases in body weight and the development of metabolic disorders; however, much is probably also related to the changes in physical activity and dietary pattern. Indeed, results of epidemiological studies suggest that a ‘western-type dietary pattern’ composed of highly processed foods, sweetened foods, and beverages, all adding to a low fiber but high sugar and saturated fat intake, may increase the odd of developing overweight and metabolic disorders. Consumption of sugar, and especially, fructose has repeatedly been discussed to be a key contributor to the development of health disturbances including hypertension, dyslipidemia, insulin resistance as well as NAFLD. However, despite intense research effort, the question if and how (high) dietary fructose intake interferes with human health has not yet been fully answered also as findings are sometimes contradictory. In the present narrative review, results of recent studies assessing the effect of fructose consumption on the development of metabolic disorders including hypertension, dyslipidemia, cardiovascular diseases (CVDs), hyperinsulinemia, and NAFLD as well as underlying molecular mechanisms are reviewed, thereby, aiming to further address the question if (high) fructose intake is a trigger of metabolic diseases.
[Names] => Anja Baumann ... Ina Bergheim [Doi] => 10.37349/edd.2022.00005 [Published] => August 29, 2022 [Viewed] => 2721 [Downloaded] => 87 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00005 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:51–71 [Recommend] => 0 [Keywords] => Dyslipidemia, fructose, hypertension, insulin resistance, non-alcoholic fatty liver disease [DetailTitle] => [DetailUrl] => [Id] => 10055 [ris] => https://www.explorationpub.com/uploads/Article/A10055/47b7f2eafe723b9aa9563acfaaa1d79d.ris [bib] => https://www.explorationpub.com/uploads/Article/A10055/529a7aaa949149b8915c5a93598763bd.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Baumann A, Brandt A, Bergheim I. Fructose, a trigger of metabolic diseases?—a narrative review. Explor Dig Dis. 2022;1:51–71. https://doi.org/10.37349/edd.2022.00005 [Jindex] => 0 [CName] => InaBergheim, [CEmail] => ina.bergheim@univie.ac.at, [Ris_Time] => 2022-08-26 01:50:09 [Bib_Time] => 2022-08-26 01:50:09 [KeysWordContens] => Fructose, a trigger of metabolic diseases?—a narrative review, Dyslipidemia, fructose, hypertension, insulin resistance, non-alcoholic fatty liver disease, Worldwide the number of individuals being overweight or obese has dramatically increased during the last decades, which is also associated with a similar dramatic increase of individuals afflicted with metabolic disorders like dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD). Genetic predisposition may account for some of the increases in body weight and the development of metabolic disorders; however, much is probably also related to the changes in physical activity and dietary pattern. Indeed, results of epidemiological studies suggest that a ‘western-type dietary pattern’ composed of highly processed foods, sweetened foods, and beverages, all adding to a low fiber but high sugar and saturated fat intake, may increase the odd of developing overweight and metabolic disorders. Consumption of sugar, and especially, fructose has repeatedly been discussed to be a key contributor to the development of health disturbances including hypertension, dyslipidemia, insulin resistance as well as NAFLD. However, despite intense research effort, the question if and how (high) dietary fructose intake interferes with human health has not yet been fully answered also as findings are sometimes contradictory. In the present narrative review, results of recent studies assessing the effect of fructose consumption on the development of metabolic disorders including hypertension, dyslipidemia, cardiovascular diseases (CVDs), hyperinsulinemia, and NAFLD as well as underlying molecular mechanisms are reviewed, thereby, aiming to further address the question if (high) fructose intake is a trigger of metabolic diseases. ,Anja Baumann ... Ina Bergheim [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [5] => Array ( [ArticleId] => 400 [Create_Time] => 2022-10-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202210/20221011005859.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10056/10056.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10056/10056.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10056/10056_cover.png [JournalsId] => 6 [Title] => The intermicrovillar adhesion complex in gut barrier function and inflammation [Abstract] => The surface of intestinal epithelial cells is covered by the brush border, which consists of densely packed cellular extrusions called microvilli. Until recently, microvilli have not been known to b [AbstractComplete] =>The surface of intestinal epithelial cells is covered by the brush border, which consists of densely packed cellular extrusions called microvilli. Until recently, microvilli have not been known to be interconnected. In 2014, a protein complex, called the intermicrovillar adhesion complex (IMAC) which is located at the tips of the microvilli and responsible for the regular spatial organization of the brush border, was identified. Deletion of IMAC components such as cadherin-related family member-2 (CDHR2) in mice resulted in microvillus disorganization and fanning, a structural aberration that is also found in the brush border of patients with inflammatory bowel disease. The etiology of inflammatory bowel disease has been primarily associated with dysfunctional mucosal immunity, but the discovery of the IMAC may encourage theories of an epithelial origin. Here, possible effects of the brush border on the gut barrier function and intestinal inflammation are discussed proposing that the IMAC protects against inflammation through its microvillus cross-linking function.
[Names] => Bernadette Mödl ... Robert Eferl [Doi] => 10.37349/edd.2022.00006 [Published] => October 11, 2022 [Viewed] => 1202 [Downloaded] => 42 [Subject] => Perspective [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00006 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:72–79 [Recommend] => 0 [Keywords] => Inflammatory bowel disease, colitis, microvilli, brush border, bacteria, microbiome, microbiota [DetailTitle] => [DetailUrl] => [Id] => 10056 [ris] => https://www.explorationpub.com/uploads/Article/A10056/f1025d1c6ade8711b3491136e35b91ac.ris [bib] => https://www.explorationpub.com/uploads/Article/A10056/e57b2ac0c51faf1cba2120b8171d994f.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Mödl B, Schmidt K, Moser D, Eferl R. The intermicrovillar adhesion complex in gut barrier function and inflammation. Explor Dig Dis. 2022;1:72–79. https://doi.org/10.37349/edd.2022.00006 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-11 03:36:18 [Bib_Time] => 2022-10-11 03:36:18 [KeysWordContens] => The intermicrovillar adhesion complex in gut barrier function and inflammation, Inflammatory bowel disease, colitis, microvilli, brush border, bacteria, microbiome, microbiota, The surface of intestinal epithelial cells is covered by the brush border, which consists of densely packed cellular extrusions called microvilli. Until recently, microvilli have not been known to be interconnected. In 2014, a protein complex, called the intermicrovillar adhesion complex (IMAC) which is located at the tips of the microvilli and responsible for the regular spatial organization of the brush border, was identified. Deletion of IMAC components such as cadherin-related family member-2 (CDHR2) in mice resulted in microvillus disorganization and fanning, a structural aberration that is also found in the brush border of patients with inflammatory bowel disease. The etiology of inflammatory bowel disease has been primarily associated with dysfunctional mucosal immunity, but the discovery of the IMAC may encourage theories of an epithelial origin. Here, possible effects of the brush border on the gut barrier function and intestinal inflammation are discussed proposing that the IMAC protects against inflammation through its microvillus cross-linking function. ,Bernadette Mödl ... Robert Eferl [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [6] => Array ( [ArticleId] => 410 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202210/20221031084447.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10057/10057.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10057/10057.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10057/10057_cover.png [JournalsId] => 6 [Title] => Caspase-2 in liver disease and hepatocellular carcinoma [Abstract] => Caspases are key factors in the regulation of the apoptotic and/or inflammatory responses, both crucial in the pathogenesis of diverse diseases. Caspase-2 is the most evolutionary conserved albeit f [AbstractComplete] =>Caspases are key factors in the regulation of the apoptotic and/or inflammatory responses, both crucial in the pathogenesis of diverse diseases. Caspase-2 is the most evolutionary conserved albeit functionally poorly defined member of the caspase family. The precise role of caspase-2 as an initiator or effector caspase is still unknown, but it has been involved in a wide variety of functions, from apoptosis to genomic stability, oxidative stress, metabolism, and cancer. However, many conflicting results render the exact function of this protease still unresolved. Although caspase-2 has several hundred substrates, the activation, processing, and activity on specific substrates remain poorly described. Recent evidence indicates that caspase-2 has a role in metabolic homeostasis and is required for lipotoxicity-induced apoptosis in hepatocytes, contributing to non-alcoholic steatohepatitis (NASH) progression towards hepatocellular carcinoma (HCC). Caspase-2 protein expression strongly localizes to injured/ballooned hepatocytes, correlating with NASH severity. Also, mice lacking caspase-2 showed protection from western diet-induced obesity, dyslipidemia, and insulin resistance. Although there are no effective therapies for NASH and HCC, the evaluation of a pan-caspase inhibitor has reached a phase I/II in clinical trials for advanced liver disease. Nevertheless, a better understanding of caspase functions with the identification of specific proteolytic substrates is essential for future therapeutic developments. Bearing in mind the pressing need to identify new targets for NASH-HCC and its metabolic-related comorbidities, and the favorable effect of caspase-2 genetic inhibition in animal models, pharmacological caspase-2 inhibition arises as a promising strategy that should be further investigated.
[Names] => Amaya Lopez-Pascual ... Maite G. Fernández-Barrena [Doi] => 10.37349/edd.2022.00007 [Published] => October 31, 2022 [Viewed] => 937 [Downloaded] => 31 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00007 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:80–96 [Recommend] => 0 [Keywords] => Caspase-2, substrates, functions, activation, cancer, DNA damage, metabolism, liver disease [DetailTitle] => [DetailUrl] => [Id] => 10057 [ris] => https://www.explorationpub.com/uploads/Article/A10057/f6b25eed75113a6087a93c711d405497.ris [bib] => https://www.explorationpub.com/uploads/Article/A10057/a9038a2c1dee72f2a60e493ae3f489c4.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Lopez-Pascual A, Cusachs M, Arechederra M, Berasain C, Herrero C, Ávila MA, et al. Caspase-2 in liver disease and hepatocellular carcinoma. Explor Dig Dis. 2022;1:80–96. https://doi.org/10.37349/edd.2022.00007 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-28 05:58:53 [Bib_Time] => 2022-10-28 05:58:53 [KeysWordContens] => Caspase-2 in liver disease and hepatocellular carcinoma, Caspase-2, substrates, functions, activation, cancer, DNA damage, metabolism, liver disease, Caspases are key factors in the regulation of the apoptotic and/or inflammatory responses, both crucial in the pathogenesis of diverse diseases. Caspase-2 is the most evolutionary conserved albeit functionally poorly defined member of the caspase family. The precise role of caspase-2 as an initiator or effector caspase is still unknown, but it has been involved in a wide variety of functions, from apoptosis to genomic stability, oxidative stress, metabolism, and cancer. However, many conflicting results render the exact function of this protease still unresolved. Although caspase-2 has several hundred substrates, the activation, processing, and activity on specific substrates remain poorly described. Recent evidence indicates that caspase-2 has a role in metabolic homeostasis and is required for lipotoxicity-induced apoptosis in hepatocytes, contributing to non-alcoholic steatohepatitis (NASH) progression towards hepatocellular carcinoma (HCC). Caspase-2 protein expression strongly localizes to injured/ballooned hepatocytes, correlating with NASH severity. Also, mice lacking caspase-2 showed protection from western diet-induced obesity, dyslipidemia, and insulin resistance. Although there are no effective therapies for NASH and HCC, the evaluation of a pan-caspase inhibitor has reached a phase I/II in clinical trials for advanced liver disease. Nevertheless, a better understanding of caspase functions with the identification of specific proteolytic substrates is essential for future therapeutic developments. Bearing in mind the pressing need to identify new targets for NASH-HCC and its metabolic-related comorbidities, and the favorable effect of caspase-2 genetic inhibition in animal models, pharmacological caspase-2 inhibition arises as a promising strategy that should be further investigated. ,Amaya Lopez-Pascual ... Maite G. Fernández-Barrena [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [7] => Array ( [ArticleId] => 412 [Create_Time] => 2022-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202210/20221031055040.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10058/10058.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10058/10058.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10058/10058_cover.png [JournalsId] => 6 [Title] => Etiopathogenesis and pathophysiology of cholestasis [Abstract] => Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duod [AbstractComplete] =>Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duodenum when it is required for the digestive process. Interruption of this secretory function results in partial or complete cholestasis, which is accompanied by important repercussions due to the lack of bile acids in the intestine and their regurgitation from hepatocytes to blood together with potentially toxic compounds that are normally eliminated in bile. The presence of active and selective transporter proteins located at both poles of the plasma membrane of hepatocytes, cholangiocytes, and epithelial cells of the ileal mucosa, together with the ability of hepatocytes to synthesize bile acids from cholesterol, enables the so-called bile acid enterohepatic circulation, which is essential in liver and gastrointestinal tract physiology. The presence in the ducts of the biliary tree of agents reducing their luminal diameter by external compression or space-occupying obstacles, either in the duct wall or its lumen, can result in total or partial obstructive cholestasis. The clinical impact and management of cholestasis are different depending on the intrahepatic or extrahepatic location of the obstacle. Thus, surgical interventions can often be helpful in removing extrahepatic obstructions and restoring normal bile flow to the duodenum. In contrast, hepatocyte or cholangiocyte damage, either global, restricted to subcellular compartments, or more specifically affecting the elements of the canalicular secretory machinery, may result in hepatocellular cholestasis or cholangiopathies. In these cases, bile flow interruption is usually partial and, except for extremely severe cases when liver transplantation is required, these patients often treated with pharmacological agents, such as ursodeoxycholic acid (UDCA) and rifampicin. The present review gathers updated information on the etiopathogenesis and pathophysiological aspects of different types of cholestasis.
[Names] => Maitane Asensio ... Jose J. G. Marin [Doi] => 10.37349/edd.2022.00008 [Published] => October 31, 2022 [Viewed] => 2045 [Downloaded] => 97 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00008 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:97–117 [Recommend] => 0 [Keywords] => Bile acid, bile flow, biliary tree, cholangiocyte, hepatocyte, secretion, transport [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 10058 [ris] => https://www.explorationpub.com/uploads/Article/A10058/912f182ec20d363b8babb1d4f8135c7f.ris [bib] => https://www.explorationpub.com/uploads/Article/A10058/5755c246e2069e28bcbbfab1adad16ab.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Asensio M, Ortiz-Rivero S, Morente-Carrasco A, Marin JJG. Etiopathogenesis and pathophysiology of cholestasis. Explor Dig Dis. 2022;1:97–117. https://doi.org/10.37349/edd.2022.00008 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-10-31 05:51:13 [Bib_Time] => 2022-10-31 05:51:13 [KeysWordContens] => Etiopathogenesis and pathophysiology of cholestasis, Bile acid, bile flow, biliary tree, cholangiocyte, hepatocyte, secretion, transport, Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duodenum when it is required for the digestive process. Interruption of this secretory function results in partial or complete cholestasis, which is accompanied by important repercussions due to the lack of bile acids in the intestine and their regurgitation from hepatocytes to blood together with potentially toxic compounds that are normally eliminated in bile. The presence of active and selective transporter proteins located at both poles of the plasma membrane of hepatocytes, cholangiocytes, and epithelial cells of the ileal mucosa, together with the ability of hepatocytes to synthesize bile acids from cholesterol, enables the so-called bile acid enterohepatic circulation, which is essential in liver and gastrointestinal tract physiology. The presence in the ducts of the biliary tree of agents reducing their luminal diameter by external compression or space-occupying obstacles, either in the duct wall or its lumen, can result in total or partial obstructive cholestasis. The clinical impact and management of cholestasis are different depending on the intrahepatic or extrahepatic location of the obstacle. Thus, surgical interventions can often be helpful in removing extrahepatic obstructions and restoring normal bile flow to the duodenum. In contrast, hepatocyte or cholangiocyte damage, either global, restricted to subcellular compartments, or more specifically affecting the elements of the canalicular secretory machinery, may result in hepatocellular cholestasis or cholangiopathies. In these cases, bile flow interruption is usually partial and, except for extremely severe cases when liver transplantation is required, these patients often treated with pharmacological agents, such as ursodeoxycholic acid (UDCA) and rifampicin. The present review gathers updated information on the etiopathogenesis and pathophysiological aspects of different types of cholestasis. ,Maitane Asensio ... Jose J. G. Marin [PublishedText] => Published [IsEdit] => 0 [AccountId] => 0 [Zh] => 1 ) [8] => Array ( [ArticleId] => 427 [Create_Time] => 2022-11-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202307/20230705020226.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10059/10059.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10059/10059.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10059/10059_cover.png [JournalsId] => 6 [Title] => Probiotic human alcohol dehydrogenase-4 expressing bacteria protects from diet-induced obesity and metabolic impairment: a new concept of disease prevention [Abstract] => Aim: Probiotic bacteria consumption for improving human health and for disease prevention is still controversial. There is a need to develop functional probiotic bacteria with proven efficacy for [AbstractComplete] =>Probiotic bacteria consumption for improving human health and for disease prevention is still controversial. There is a need to develop functional probiotic bacteria with proven efficacy for the human gastrointestinal (GI) system. The novel bacteria will lower the steady state of constant Ethanol production may lead to gut microbiota dysbiosis and liver injuries.
Herein engineered probiotic bacterium B. subtilis to enhance the secretion of human alcohol dehydrogenase-4 (ADH4) by fusion of signal peptides (SPs) was constructed. As a result, higher ADH4 secretion and Ethanol removal rates were observed in phoB SP transformant SP-64, compared to other transformants. The engineered ADH4 expressing probiotic B. subtilis was delivered as spores to evaluate various physiological, biochemical, and immuno-histochemical parameters of mice under a high-fat diet (HFD)-induced obesity and metabolic impairment.
The treatment ameliorated significantly weight gain, improved glucose utilization, and prevented HFD-induced pancreatic damage. Lastly, SP-64 inoculation altered the gut microbiota, and increased the Firmicutes/Bacteroides ratio, supporting better fitness under HFD.
SP-64 emerged as a potential probiotic that opens a new avenue for interventions against over-nutrition-induced metabolic disorders.
Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment.
[Names] => Ricardo Espinosa-Escudero ... Maria J. Monte [Doi] => 10.37349/edd.2022.00010 [Published] => December 7, 2022 [Viewed] => 977 [Downloaded] => 43 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00010 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:137–153 [Recommend] => 0 [Keywords] => Bile acid, cholestasis, genetic disorders, hepatitis, inborn errors, liver failure, metabolism [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100510 [ris] => https://www.explorationpub.com/uploads/Article/A100510/048fa87a4b2820de3bb0e8157d418f68.ris [bib] => https://www.explorationpub.com/uploads/Article/A100510/206179e3903baf4684301cbe2084160e.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Espinosa-Escudero R, Herraez E, Sanchez-Martin A, Sanchon-Sanchez P, Marin JJG, Monte MJ. Cholestasis associated to inborn errors in bile acid synthesis. Explor Dig Dis. 2022;1:137–53. https://doi.org/10.37349/edd.2022.00010 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-05 07:16:09 [Bib_Time] => 2022-12-05 07:16:09 [KeysWordContens] => Cholestasis associated to inborn errors in bile acid synthesis, Bile acid, cholestasis, genetic disorders, hepatitis, inborn errors, liver failure, metabolism, Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment. ,Ricardo Espinosa-Escudero ... Maria J. Monte [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [10] => Array ( [ArticleId] => 457 [Create_Time] => 2022-12-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202212/20221230032821.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100511/100511.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100511/100511.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100511/100511_cover.png [JournalsId] => 6 [Title] => The bile acid receptor TGR5 and cholestasis [Abstract] => Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the he [AbstractComplete] =>During liver injury and cholestasis, the mechanisms allowing the organ to protect itself with the aim of maintaining biliary homeostasis are not completely understood. Central to their biological roles, bile acids (BAs) and their receptors constitute a signaling network with multiple molecular and cellular impacts on both liver repair and protection from BA overload. BA signal through nuclear [mainly farnesoid X receptor (FXR)] and membrane [mainly G protein-coupled BA receptor 1 (GPBAR-1), aka Takeda G protein-coupled receptor 5 (TGR5)] receptors, in which activation elicits a wide array of biological responses. So far, most of the studies have been focused on FXR signaling as hepato-protective, TGR5 being less explored to this regard. While the liver faces massive and potentially harmful BA overload during cholestasis, it is crucial to understand that BAs induce also protective responses contributing not only to reduce the inflammatory burden, but also to spare liver cells and their repair capacities. Based on the available literature, the TGR5 BA receptor protects the liver in the cholestatic context and counteracts BA overload with the aim of restoring biliary homeostasis mainly through the control of inflammatory processes, biliary epithelial barrier permeability, and BA pool composition. Mouse experimental models of cholestasis reveal that the lack of TGR5 was associated with exacerbated inflammation and necrosis, leaky biliary epithelium, and excessive BA pool hydrophobicity, resulting in biliary cell and parenchymal insult, and compromising optimal restoration of biliary homeostasis and liver repair. There are thus widely opened translational perspectives with the aim of targeting TGR5-related signaling or biological responses to trigger protection of the cholestatic liver.
[Names] => Grégory Merlen ... Thierry Tordjmann [Doi] => 10.37349/edd.2022.00011 [Published] => December 30, 2022 [Viewed] => 907 [Downloaded] => 42 [Subject] => Review [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00012 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:154–169 [Recommend] => 0 [Keywords] => Liver, bile acids, cholestasis, Takeda G protein-coupled receptor 5 (TGR5), hepatoprotection [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100511 [ris] => https://www.explorationpub.com/uploads/Article/A100511/0306b5196c2fc42195d1696a883664b5.ris [bib] => https://www.explorationpub.com/uploads/Article/A100511/97adbb4b5c122fd4055fe1560877ac10.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Merlen G, Bidault-Jourdainne V, Doignon I, Garcin I, Tordjmann T. The bile acid receptor TGR5 and cholestasis. Explor Dig Dis. 2022;1:154–69. https://doi.org/10.37349/edd.2022.00011 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-29 07:05:02 [Bib_Time] => 2022-12-29 07:05:02 [KeysWordContens] => The bile acid receptor TGR5 and cholestasis, Liver, bile acids, cholestasis, Takeda G protein-coupled receptor 5 (TGR5), hepatoprotection, During liver injury and cholestasis, the mechanisms allowing the organ to protect itself with the aim of maintaining biliary homeostasis are not completely understood. Central to their biological roles, bile acids (BAs) and their receptors constitute a signaling network with multiple molecular and cellular impacts on both liver repair and protection from BA overload. BA signal through nuclear [mainly farnesoid X receptor (FXR)] and membrane [mainly G protein-coupled BA receptor 1 (GPBAR-1), aka Takeda G protein-coupled receptor 5 (TGR5)] receptors, in which activation elicits a wide array of biological responses. So far, most of the studies have been focused on FXR signaling as hepato-protective, TGR5 being less explored to this regard. While the liver faces massive and potentially harmful BA overload during cholestasis, it is crucial to understand that BAs induce also protective responses contributing not only to reduce the inflammatory burden, but also to spare liver cells and their repair capacities. Based on the available literature, the TGR5 BA receptor protects the liver in the cholestatic context and counteracts BA overload with the aim of restoring biliary homeostasis mainly through the control of inflammatory processes, biliary epithelial barrier permeability, and BA pool composition. Mouse experimental models of cholestasis reveal that the lack of TGR5 was associated with exacerbated inflammation and necrosis, leaky biliary epithelium, and excessive BA pool hydrophobicity, resulting in biliary cell and parenchymal insult, and compromising optimal restoration of biliary homeostasis and liver repair. There are thus widely opened translational perspectives with the aim of targeting TGR5-related signaling or biological responses to trigger protection of the cholestatic liver. ,Grégory Merlen ... Thierry Tordjmann [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [11] => Array ( [ArticleId] => 465 [Create_Time] => 2022-12-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202212/20221230054526.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100512/100512.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100512/100512.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100512/100512_cover.png [JournalsId] => 6 [Title] => Hypoxia signaling and cholesterol/steroidogenic acute regulatory protein 1 axis: interplay and role in alcohol and non-alcohol-related liver diseases [Abstract] => Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the he [AbstractComplete] =>Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the hepatic parenchyma. As a master regulator of hypoxia, the transcription factor hypoxia-inducing factor (HIF) is stabilized primarily by oxygen availability, and it is thought to contribute to steatohepatitis due to alcohol-related (ASH) and non-alcohol-related liver disease (NASH). Cholesterol has emerged as an important player in both diseases, and hypoxia increases hepatic cholesterol levels. Steroidogenic acute regulatory protein 1 (STARD1) is a mitochondrial outer membrane protein that transfers cholesterol to mitochondrial inner membrane for metabolic processing and acts as the rate-limiting step in the alternative pathway of bile acid synthesis in hepatocytes. STARD1 expression increases in ASH and NASH and determines the accumulation of cholesterol in mitochondria, which impacts the physico-chemical mitochondrial membranes properties and as a consequence impairs the activity of specific mitochondrial solute carriers, such as the 2-oxoglutarate carrier (2-OGC), limiting the exchange between cytosolic glutathione and mitochondrial 2-oxoglutarate (2-OG). Although HIF-1 is stabilized in hypoxia largely due to the requirement of prolylhydroxylases (PHDs) for oxygen to signal HIF degradation, PHDs are also dependent on 2-OG, and therefore it is conceivable that impairment of 2-OGC by STARD1-mediated cholesterol accumulation may contribute to HIF-1 stabilization due in part to decreased availability of cytosolic 2-OG. In this perspective, this review explores the interplay between HIF-1 stabilization and STARD1 induction and the potential contribution of this functional relationship to ASH and NASH.
[Names] => Sandra Torres ... Carmen Garcia-Ruiz [Doi] => 10.37349/edd.2022.00012 [Published] => December 30, 2022 [Viewed] => 707 [Downloaded] => 41 [Subject] => Perspective [Year] => 2022 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2022.00012 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2022;1:170–186 [Recommend] => 0 [Keywords] => Hypoxia, cholesterol transport, mitochondria, reactive oxygen species [DetailTitle] => [DetailUrl] => [Id] => 100512 [ris] => https://www.explorationpub.com/uploads/Article/A100512/b4b09d686bf7f7335ce4cc0a5b5c0a25.ris [bib] => https://www.explorationpub.com/uploads/Article/A100512/4155d2398d1f568b1e8f5eea93662765.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Torres S, Fernandez-Checa JC, Garcia-Ruiz C. Hypoxia signaling and cholesterol/steroidogenic acute regulatory protein 1 axis: interplay and role in alcohol and non-alcohol-related liver diseases. Explor Dig Dis. 2022;1:170–86. https://doi.org/10.37349/edd.2022.00012 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2022-12-29 01:35:19 [Bib_Time] => 2022-12-29 01:35:19 [KeysWordContens] => Hypoxia signaling and cholesterol/steroidogenic acute regulatory protein 1 axis: interplay and role in alcohol and non-alcohol-related liver diseases, Hypoxia, cholesterol transport, mitochondria, reactive oxygen species, Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the hepatic parenchyma. As a master regulator of hypoxia, the transcription factor hypoxia-inducing factor (HIF) is stabilized primarily by oxygen availability, and it is thought to contribute to steatohepatitis due to alcohol-related (ASH) and non-alcohol-related liver disease (NASH). Cholesterol has emerged as an important player in both diseases, and hypoxia increases hepatic cholesterol levels. Steroidogenic acute regulatory protein 1 (STARD1) is a mitochondrial outer membrane protein that transfers cholesterol to mitochondrial inner membrane for metabolic processing and acts as the rate-limiting step in the alternative pathway of bile acid synthesis in hepatocytes. STARD1 expression increases in ASH and NASH and determines the accumulation of cholesterol in mitochondria, which impacts the physico-chemical mitochondrial membranes properties and as a consequence impairs the activity of specific mitochondrial solute carriers, such as the 2-oxoglutarate carrier (2-OGC), limiting the exchange between cytosolic glutathione and mitochondrial 2-oxoglutarate (2-OG). Although HIF-1 is stabilized in hypoxia largely due to the requirement of prolylhydroxylases (PHDs) for oxygen to signal HIF degradation, PHDs are also dependent on 2-OG, and therefore it is conceivable that impairment of 2-OGC by STARD1-mediated cholesterol accumulation may contribute to HIF-1 stabilization due in part to decreased availability of cytosolic 2-OG. In this perspective, this review explores the interplay between HIF-1 stabilization and STARD1 induction and the potential contribution of this functional relationship to ASH and NASH. ,Sandra Torres ... Carmen Garcia-Ruiz [PublishedText] => Published [IsEdit] => 0 [AccountId] => 38 [Zh] => 1 ) [12] => Array ( [ArticleId] => 473 [Create_Time] => 2023-02-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202302/20230225062519.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100513/100513.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100513/100513.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100513/100513_cover.png [JournalsId] => 6 [Title] => Lysosomal hydrolases, from waste-bags effectors to essential multipurpose enzymes in liver fibrosis [Abstract] => Lysosomal hydrolases were once considered effectors of the waste disposal system of the cell, the endo-lysosomal system. However, they are now recognized as highly selective enzymes, which can modul [AbstractComplete] =>Lysosomal hydrolases were once considered effectors of the waste disposal system of the cell, the endo-lysosomal system. However, they are now recognized as highly selective enzymes, which can modulate the function of several substrates, contributing to essential homeostatic and pathological cellular processes. There are more than 50 different lysosomal hydrolases that display optimal activity in the pH present in the acidic cellular compartment but can also be found in other cellular locations. They can work alone or in cooperation with other proteases building signaling pathways or amplification cascades. In the context of liver fibrosis lysosomal hydrolases, especially cysteine cathepsins have been described to participate in several fundamental cellular events contributing to the development, progression, perpetuation, and resolution of liver fibrosis. This paper comprehensively reviews the current knowledge on the contribution of lysosomal hydrolases to liver fibrosis.
[Names] => María Fernández-Fernández ... Anna Moles [Doi] => 10.37349/edd.2023.00013 [Published] => February 22, 2023 [Viewed] => 636 [Downloaded] => 30 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00013 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:1–10 [Recommend] => 0 [Keywords] => Lysosome, protease, cathepsin, liver fibrosis [DetailTitle] => [DetailUrl] => [Id] => 100513 [ris] => https://www.explorationpub.com/uploads/Article/A100513/d8187433f4dd613352f6719b712b7103.ris [bib] => https://www.explorationpub.com/uploads/Article/A100513/9b88b0e3568b39c60541869afe5adf3f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Fernández-Fernández M, Ruiz-Blázquez P, Cacho-Pujol J, Moles A. Lysosomal hydrolases, from waste-bags effectors to essential multipurpose enzymes in liver fibrosis. Explor Dig Dis. 2023;2:1–10. https://doi.org/10.37349/edd.2023.00013 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-28 07:24:46 [Bib_Time] => 2023-02-28 07:24:46 [KeysWordContens] => Lysosomal hydrolases, from waste-bags effectors to essential multipurpose enzymes in liver fibrosis, Lysosome, protease, cathepsin, liver fibrosis, Lysosomal hydrolases were once considered effectors of the waste disposal system of the cell, the endo-lysosomal system. However, they are now recognized as highly selective enzymes, which can modulate the function of several substrates, contributing to essential homeostatic and pathological cellular processes. There are more than 50 different lysosomal hydrolases that display optimal activity in the pH present in the acidic cellular compartment but can also be found in other cellular locations. They can work alone or in cooperation with other proteases building signaling pathways or amplification cascades. In the context of liver fibrosis lysosomal hydrolases, especially cysteine cathepsins have been described to participate in several fundamental cellular events contributing to the development, progression, perpetuation, and resolution of liver fibrosis. This paper comprehensively reviews the current knowledge on the contribution of lysosomal hydrolases to liver fibrosis. ,María Fernández-Fernández ... Anna Moles [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [13] => Array ( [ArticleId] => 480 [Create_Time] => 2023-02-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202302/20230227111957.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100514/100514.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100514/100514.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100514/100514_cover.png [JournalsId] => 6 [Title] => Extra-hepatic cancers in metabolic fatty liver syndromes [Abstract] => [AbstractComplete] => [Names] => Amedeo Lonardo [Doi] => 10.37349/edd.2023.00014 [Published] => February 24, 2023 [Viewed] => 840 [Downloaded] => 29 [Subject] => Editorial [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00014 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:11–17 [Recommend] => 0 [Keywords] => [DetailTitle] => [DetailUrl] => [Id] => 100514 [ris] => https://www.explorationpub.com/uploads/Article/A100514/4158ebc4f038f8fe547c4a0c924e5950.ris [bib] => https://www.explorationpub.com/uploads/Article/A100514/85b1e4207f89e1261a73134245b8c325.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-26 [CitethisArticle] => Lonardo A. Extra-hepatic cancers in metabolic fatty liver syndromes. Explor Dig Dis. 2023;2:11–7. https://doi.org/10.37349/edd.2023.00014 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-22 02:08:33 [Bib_Time] => 2023-02-22 02:08:33 [KeysWordContens] => Extra-hepatic cancers in metabolic fatty liver syndromes,,,Amedeo Lonardo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 58 [Zh] => 1 ) [14] => Array ( [ArticleId] => 513 [Create_Time] => 2023-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202302/20230228065333.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100515/100515.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100515/100515.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100515/100515_cover.png [JournalsId] => 6 [Title] => Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds [Abstract] => Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds. [AbstractComplete] =>Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds.
[Names] => Beatriz Sanchez de Blas ... Marta R. Romero [Doi] => 10.37349/edd.2023.00015 [Published] => February 28, 2023 [Viewed] => 755 [Downloaded] => 34 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00015 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:18–33 [Recommend] => 0 [Keywords] => Bile, bile acid, cholephilic compounds, cholestasis, liver failure, transport [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100515 [ris] => https://www.explorationpub.com/uploads/Article/A100515/8abe4c1ba4d0d656868d07a575fdc55b.ris [bib] => https://www.explorationpub.com/uploads/Article/A100515/c0023c98aae5771e46e466db3b6cd669.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => de Blas BS, Temprano AG, Marin JJG, Romero MR. Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds. Explor Dig Dis. 2023;2:18–33. https://doi.org/10.37349/edd.2023.00015 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-27 07:44:10 [Bib_Time] => 2023-02-27 07:44:10 [KeysWordContens] => Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds, Bile, bile acid, cholephilic compounds, cholestasis, liver failure, transport, Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds. ,Beatriz Sanchez de Blas ... Marta R. Romero [PublishedText] => Published [IsEdit] => 0 [AccountId] => 47 [Zh] => 1 ) [15] => Array ( [ArticleId] => 530 [Create_Time] => 2023-04-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230421033117.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100516/100516.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100516/100516.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100516/100516_cover.png [JournalsId] => 6 [Title] => Diagnostic workup of suspected hereditary cholestasis in adults: a case report [Abstract] => Hereditary cholestasis comprises a broad spectrum of clinical phenotypes of varying severity. Severe forms such as progressive familial intrahepatic cholestasis (PFIC) mostly affect children with di [AbstractComplete] =>Hereditary cholestasis comprises a broad spectrum of clinical phenotypes of varying severity. Severe forms such as progressive familial intrahepatic cholestasis (PFIC) mostly affect children with disease onset within their first years. Nevertheless, late-onset PFIC forms are increasingly diagnosed. Most adults present with less severe forms of hereditary cholestasis, often suffering from pruritus, gallstone disease, jaundice, or elevated liver enzymes. To identify the underlying genetic background and to rule out potential differential diagnoses, a broad genetic analysis like whole exome sequencing (WES) is recommended. Knowledge of the affected gene may have an impact not only on patient surveillance due to risk for disease progression or tumor development but also on potential therapeutic strategies. This case of the adult patient illustrates the importance of broad genetic analysis, which brought up the potentially relevant rare multidrug resistance protein 3 (MDR3) missense variant p.(Asn489Tyr) underlying the patient’s clinical phenotype of low phospholipid-associated cholelithiasis (LPAC). Patients with MDR3 disease may have an increased risk for cholangiocarcinoma (CCA) development and therefore need an individualized surveillance strategy. Most MDR3-affected patients benefit from life-long therapy with ursodeoxycholic acid (UDCA), which is well tolerated. Bezafibrate treatment can reduce pruritus, one of the main symptoms affecting the quality of life. Whether the administration of ileal bile acid transporter (IBAT) inhibitors is beneficial in adult patients with MDR3 disease is so far unknown.
[Names] => Carola Dröge ... Verena Keitel [Doi] => 10.37349/edd.2023.00016 [Published] => April 21, 2023 [Viewed] => 924 [Downloaded] => 44 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00016 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:34–43 [Recommend] => 0 [Keywords] => Hereditary cholestasis, low phospholipid-associated cholelithiasis (LPAC), genetic analysis, farnesoid X receptor (FXR), multidrug resistance protein 3 (MDR3), registry [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100516 [ris] => https://www.explorationpub.com/uploads/Article/A100516/edd4105460d8277134d0ac74f42ace2c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100516/b65931b9140c21c5f7324f1d4f9816e9.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Dröge C, Götze T, Behrendt A, Gohlke H, Keitel V. Diagnostic workup of suspected hereditary cholestasis in adults: a case report. Explor Dig Dis. 2023;2:34–43. https://doi.org/10.37349/edd.2023.00016 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-18 09:57:37 [Bib_Time] => 2023-04-18 09:57:37 [KeysWordContens] => Diagnostic workup of suspected hereditary cholestasis in adults: a case report, Hereditary cholestasis, low phospholipid-associated cholelithiasis (LPAC), genetic analysis, farnesoid X receptor (FXR), multidrug resistance protein 3 (MDR3), registry, Hereditary cholestasis comprises a broad spectrum of clinical phenotypes of varying severity. Severe forms such as progressive familial intrahepatic cholestasis (PFIC) mostly affect children with disease onset within their first years. Nevertheless, late-onset PFIC forms are increasingly diagnosed. Most adults present with less severe forms of hereditary cholestasis, often suffering from pruritus, gallstone disease, jaundice, or elevated liver enzymes. To identify the underlying genetic background and to rule out potential differential diagnoses, a broad genetic analysis like whole exome sequencing (WES) is recommended. Knowledge of the affected gene may have an impact not only on patient surveillance due to risk for disease progression or tumor development but also on potential therapeutic strategies. This case of the adult patient illustrates the importance of broad genetic analysis, which brought up the potentially relevant rare multidrug resistance protein 3 (MDR3) missense variant p.(Asn489Tyr) underlying the patient’s clinical phenotype of low phospholipid-associated cholelithiasis (LPAC). Patients with MDR3 disease may have an increased risk for cholangiocarcinoma (CCA) development and therefore need an individualized surveillance strategy. Most MDR3-affected patients benefit from life-long therapy with ursodeoxycholic acid (UDCA), which is well tolerated. Bezafibrate treatment can reduce pruritus, one of the main symptoms affecting the quality of life. Whether the administration of ileal bile acid transporter (IBAT) inhibitors is beneficial in adult patients with MDR3 disease is so far unknown. ,Carola Dröge ... Verena Keitel [PublishedText] => Published [IsEdit] => 0 [AccountId] => 48 [Zh] => 1 ) [16] => Array ( [ArticleId] => 531 [Create_Time] => 2023-04-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230427015327.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100517/100517.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100517/100517.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100517/100517_cover.png [JournalsId] => 6 [Title] => Zebrafish as a model for drug induced liver injury: state of the art and beyond [Abstract] => Zebrafish as a preclinical drug induced liver injury (DILI) model provides multiple advantages ranging from ease of breeding and maintenance, availability of different strains and transgenic fish am [AbstractComplete] =>Zebrafish as a preclinical drug induced liver injury (DILI) model provides multiple advantages ranging from ease of breeding and maintenance, availability of different strains and transgenic fish amenable to study liver function, and highly conserved liver structure and function with the human liver. In this review, the authors have aimed to provide an account of the metabolic enzymes that take roles in drug detoxification in both human and zebrafish in a comparative manner and exemplify several recent models in studying liver functionality. Moreover, the authors emphasize the difficulties associated with studying idiosyncratic DILI in preclinical models and propose that zebrafish could be an important complement to mice in testing functions of genes that are associated with DILI with respect to different drugs in human genome-wide association studies (GWAS) Catalog. Finally, this review highlights the state-of-the-art in the development of novel transgenic reporter strains that can be used to study degree and molecular mechanisms of hepatotoxicity caused by drugs in zebrafish. All of these will help researchers to use effectively the available resources in the zebrafish DILI models, while advocating potential leads that can be taken to provide advancements in a better understanding and treatment of DILI.
[Names] => Gulcin Cakan-Akdogan ... Ozlen Konu [Doi] => 10.37349/edd.2023.00017 [Published] => April 26, 2023 [Viewed] => 1368 [Downloaded] => 69 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00017 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 97 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:44–55 [Recommend] => 0 [Keywords] => Drug induced liver injury, zebrafish, reporter lines, genome-wide association studies [DetailTitle] => Drug-induced Liver Injury: From Bench to Clinical Application [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/97 [Id] => 100517 [ris] => https://www.explorationpub.com/uploads/Article/A100517/7eb854209b30d9b13b93a36523d6f3d3.ris [bib] => https://www.explorationpub.com/uploads/Article/A100517/aa631b514cd24344f37db1eb4df08017.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Cakan-Akdogan G, Aftab AM, Cinar MC, Abdelhalim KA, Konu O. Zebrafish as a model for drug induced liver injury: state of the art and beyond. Explor Dig Dis. 2023;2:44–55. https://doi.org/10.37349/edd.2023.00017 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-11 02:41:28 [Bib_Time] => 2023-04-27 01:50:52 [KeysWordContens] => Zebrafish as a model for drug induced liver injury: state of the art and beyond, Drug induced liver injury, zebrafish, reporter lines, genome-wide association studies, Zebrafish as a preclinical drug induced liver injury (DILI) model provides multiple advantages ranging from ease of breeding and maintenance, availability of different strains and transgenic fish amenable to study liver function, and highly conserved liver structure and function with the human liver. In this review, the authors have aimed to provide an account of the metabolic enzymes that take roles in drug detoxification in both human and zebrafish in a comparative manner and exemplify several recent models in studying liver functionality. Moreover, the authors emphasize the difficulties associated with studying idiosyncratic DILI in preclinical models and propose that zebrafish could be an important complement to mice in testing functions of genes that are associated with DILI with respect to different drugs in human genome-wide association studies (GWAS) Catalog. Finally, this review highlights the state-of-the-art in the development of novel transgenic reporter strains that can be used to study degree and molecular mechanisms of hepatotoxicity caused by drugs in zebrafish. All of these will help researchers to use effectively the available resources in the zebrafish DILI models, while advocating potential leads that can be taken to provide advancements in a better understanding and treatment of DILI. ,Gulcin Cakan-Akdogan ... Ozlen Konu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 21 [Zh] => 1 ) [17] => Array ( [ArticleId] => 532 [Create_Time] => 2023-04-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230428010227.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100518/100518.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100518/100518.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100518/100518_cover.png [JournalsId] => 6 [Title] => Immunophenotyping to improve the mechanistic understanding of idiosyncratic drug-induced liver injury: clinical implications and future directions [Abstract] => The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) a [AbstractComplete] =>The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) alleles with DILI due to specific drugs support the crucial role of the immune system (both innate and adaptive) in the pathogenesis of DILI. Recent advances in both flow and mass cytometry have allowed the profiling of all major immune cell types in a given sample. Therefore, determining the lymphocyte populations in samples from patients with DILI would facilitate the development of specific biomarkers for DILI diagnosis and prognosis. To date, a few studies have explored the immune landscape in DILI. In a recent study of leukocyte immunophenotyping using flow cytometry from the Spanish DILI Registry, an important role of adaptive immune response in DILI is suggested. DILI patients had significantly higher levels of T helper 1 (Th1) cells and activated helper and cytotoxic T cells than healthy controls. Furthermore, the increased expression of negative immune checkpoints and ligands in DILI patients could reflect a restoration of the immune homeostasis. Differences in the profile of cytokines in DILI patients from the Drug-Induced Liver Injury Network (DILIN) also suggest an involvement of both innate and adaptive immune systems in DILI development and prognosis. Moreover, several studies based on immunophenotyping of liver infiltrates showed a distinctive pattern of cellular infiltrates in patients with immune checkpoint inhibitors (ICIs)-DILI, with lower levels of plasma cells, CD20+ B cells and CD4+ T cells than in autoimmune hepatitis (AIH) patients. These pioneering studies highlight the importance of immunophenotyping for the mechanistic understanding of DILI. In this review, available data on immunophenotyping in DILI are gathered, and the potential clinical applications of cutting-edge, novel immunophenotyping techniques are discussed.
[Names] => Alejandro Cueto-Sánchez ... Marina Villanueva-Paz [Doi] => 10.37349/edd.2023.00018 [Published] => April 26, 2023 [Viewed] => 1135 [Downloaded] => 60 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00018 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 97 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:56–76 [Recommend] => 0 [Keywords] => Hepatotoxicity, drug-induced liver injury (DILI), immune tolerance, immune system, immunophenotyping, diagnosis, mechanisms [DetailTitle] => Drug-induced Liver Injury: From Bench to Clinical Application [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/97 [Id] => 100518 [ris] => https://www.explorationpub.com/uploads/Article/A100518/da4c62a7008714d8ae5253cea9d53075.ris [bib] => https://www.explorationpub.com/uploads/Article/A100518/df91c2edb47a42cc61951991da52bfbe.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Cueto-Sánchez A, Di Zeo-Sánchez DE, Segovia-Zafra A, Matilla-Cabello G, Bodoque-García A, Lucena MI, et al. Immunophenotyping to improve the mechanistic understanding of idiosyncratic drug-induced liver injury: clinical implications and future directions. Explor Dig Dis. 2023;2:56–76. https://doi.org/10.37349/edd.2023.00018 [Jindex] => 0 [CName] => María IsabelLucena, [CEmail] => lucena@uma.es, [Ris_Time] => 2023-04-18 08:30:49 [Bib_Time] => 2023-04-18 08:30:49 [KeysWordContens] => Immunophenotyping to improve the mechanistic understanding of idiosyncratic drug-induced liver injury: clinical implications and future directions, Hepatotoxicity, drug-induced liver injury (DILI), immune tolerance, immune system, immunophenotyping, diagnosis, mechanisms, The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) alleles with DILI due to specific drugs support the crucial role of the immune system (both innate and adaptive) in the pathogenesis of DILI. Recent advances in both flow and mass cytometry have allowed the profiling of all major immune cell types in a given sample. Therefore, determining the lymphocyte populations in samples from patients with DILI would facilitate the development of specific biomarkers for DILI diagnosis and prognosis. To date, a few studies have explored the immune landscape in DILI. In a recent study of leukocyte immunophenotyping using flow cytometry from the Spanish DILI Registry, an important role of adaptive immune response in DILI is suggested. DILI patients had significantly higher levels of T helper 1 (Th1) cells and activated helper and cytotoxic T cells than healthy controls. Furthermore, the increased expression of negative immune checkpoints and ligands in DILI patients could reflect a restoration of the immune homeostasis. Differences in the profile of cytokines in DILI patients from the Drug-Induced Liver Injury Network (DILIN) also suggest an involvement of both innate and adaptive immune systems in DILI development and prognosis. Moreover, several studies based on immunophenotyping of liver infiltrates showed a distinctive pattern of cellular infiltrates in patients with immune checkpoint inhibitors (ICIs)-DILI, with lower levels of plasma cells, CD20+ B cells and CD4+ T cells than in autoimmune hepatitis (AIH) patients. These pioneering studies highlight the importance of immunophenotyping for the mechanistic understanding of DILI. In this review, available data on immunophenotyping in DILI are gathered, and the potential clinical applications of cutting-edge, novel immunophenotyping techniques are discussed. ,Alejandro Cueto-Sánchez ... Marina Villanueva-Paz [PublishedText] => Published [IsEdit] => 0 [AccountId] => 57 [Zh] => 1 ) [18] => Array ( [ArticleId] => 609 [Create_Time] => 2023-06-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630025913.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100519/100519.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100519/100519.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100519/100519_cover.png [JournalsId] => 6 [Title] => Liver injury related to Japanese herbal medicines: clinical features and diagnosis [Abstract] => The word “Kampo medicine” means the traditional Japanese herbal medicine. Even “natural herb” can cause drug-induced liver injury (DILI). In this review, the characteristics of Kampo medicin [AbstractComplete] =>The word “Kampo medicine” means the traditional Japanese herbal medicine. Even “natural herb” can cause drug-induced liver injury (DILI). In this review, the characteristics of Kampo medicine-induced liver injury (KMILI) are reported. The main causative herb involved in Kampo medicine is Scutellariae Radix. KMILI is based on certain hypersensitivity reactions. A small amount of Kampo medicine can cause liver injury, and KMILI can develop after a short latency period. The incidence of liver injury related to Scutellariae Radix is about 1%. KMILI is usually mild and not fatal. The latency period usually lasts 4 weeks to 24 weeks. Fatigue and loss of appetite are sometimes observed. Eosinophilia is not frequently observed. All three types of liver injuries are observed in KMILI: cholestatic, hepatocellular, and mixed types. In Japan, lymphocyte transformation test (LTT) has been generally used for the diagnosis of DILI; however, LTT is likely to yield false-positive result for Kampo medicines, and thus often leads to misdiagnosis in many cases. Recently, researchers reported that a specific human leukocyte antigen (HLA) genotype is possibly associated with KMILI. This hypothesis needs to be examined further. Although Kampo medicine is based on rich knowledge and experience that occurred over a period of thousands of years, much is still unknown about KMILI.
[Names] => Naoki Mantani [Doi] => 10.37349/edd.2023.00019 [Published] => June 27, 2023 [Viewed] => 534 [Downloaded] => 12 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00019 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 97 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:77–82 [Recommend] => 0 [Keywords] => Drug-induced liver injury, Kampo medicine, incidence, lymphocyte transformation test, human leukocyte antigen [DetailTitle] => Drug-induced Liver Injury: From Bench to Clinical Application [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/97 [Id] => 100519 [ris] => https://www.explorationpub.com/uploads/Article/A100519/33cc74d69b0e4c653fc749573ef0d6c7.ris [bib] => https://www.explorationpub.com/uploads/Article/A100519/35593ddc622568c519a2322a5e30151b.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Mantani N. Liver injury related to Japanese herbal medicines: clinical features and diagnosis. Explor Dig Dis. 2023;2:77–82. https://doi.org/10.37349/edd.2023.00019 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-26 02:00:20 [Bib_Time] => 2023-06-26 02:00:20 [KeysWordContens] => Liver injury related to Japanese herbal medicines: clinical features and diagnosis, Drug-induced liver injury, Kampo medicine, incidence, lymphocyte transformation test, human leukocyte antigen, The word “Kampo medicine” means the traditional Japanese herbal medicine. Even “natural herb” can cause drug-induced liver injury (DILI). In this review, the characteristics of Kampo medicine-induced liver injury (KMILI) are reported. The main causative herb involved in Kampo medicine is Scutellariae Radix. KMILI is based on certain hypersensitivity reactions. A small amount of Kampo medicine can cause liver injury, and KMILI can develop after a short latency period. The incidence of liver injury related to Scutellariae Radix is about 1%. KMILI is usually mild and not fatal. The latency period usually lasts 4 weeks to 24 weeks. Fatigue and loss of appetite are sometimes observed. Eosinophilia is not frequently observed. All three types of liver injuries are observed in KMILI: cholestatic, hepatocellular, and mixed types. In Japan, lymphocyte transformation test (LTT) has been generally used for the diagnosis of DILI; however, LTT is likely to yield false-positive result for Kampo medicines, and thus often leads to misdiagnosis in many cases. Recently, researchers reported that a specific human leukocyte antigen (HLA) genotype is possibly associated with KMILI. This hypothesis needs to be examined further. Although Kampo medicine is based on rich knowledge and experience that occurred over a period of thousands of years, much is still unknown about KMILI. ,Naoki Mantani [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [19] => Array ( [ArticleId] => 610 [Create_Time] => 2023-06-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230627004127.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100520/100520.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100520/100520.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100520/100520_Cover.png [JournalsId] => 6 [Title] => Role of oxidative stress and endoplasmic reticulum stress in drug-induced liver injury [Abstract] => The pathogenesis of drug-induced liver injury (DILI) is still in an early stage of research. However, investigators have shown that both oxidative stress and endoplasmic reticulum (ER) stress play a [AbstractComplete] =>The pathogenesis of drug-induced liver injury (DILI) is still in an early stage of research. However, investigators have shown that both oxidative stress and endoplasmic reticulum (ER) stress play a significant role in the pathological mechanism. However, there is little in-depth literature about these two mechanisms. In order to prevent and improve the clinical symptoms of DILI, it is particularly important to study its pathogenesis. In this review article, the role of ER and oxidative stress in DILI is thoroughly discussed.
[Names] => Hanghang Wu ... Francisco Javier Cubero [Doi] => 10.37349/edd.2023.00020 [Published] => June 28, 2023 [Viewed] => 1666 [Downloaded] => 48 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00020 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 97 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:83–99 [Recommend] => 1 [Keywords] => Reactive nitrogen species, reactive oxygen species, endoplasmic reticulum stress, unfolded protein response, drug-induced liver injury [DetailTitle] => Drug-induced Liver Injury: From Bench to Clinical Application [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/97 [Id] => 100520 [ris] => https://www.explorationpub.com/uploads/Article/A100520/d2e8ded9840d338940dd8fa4dc159545.ris [bib] => https://www.explorationpub.com/uploads/Article/A100520/acae9741335f76b63533bb8b833185d8.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Wu H, Bao X, Gutierrez AH, Nevzorova YA, Cubero FJ. Role of oxidative stress and endoplasmic reticulum stress in drug-induced liver injury. Explor Dig Dis. 2023;2:83–99. https://doi.org/10.37349/edd.2023.00020 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-26 03:14:44 [Bib_Time] => 2023-06-26 03:14:44 [KeysWordContens] => Role of oxidative stress and endoplasmic reticulum stress in drug-induced liver injury, Reactive nitrogen species, reactive oxygen species, endoplasmic reticulum stress, unfolded protein response, drug-induced liver injury, The pathogenesis of drug-induced liver injury (DILI) is still in an early stage of research. However, investigators have shown that both oxidative stress and endoplasmic reticulum (ER) stress play a significant role in the pathological mechanism. However, there is little in-depth literature about these two mechanisms. In order to prevent and improve the clinical symptoms of DILI, it is particularly important to study its pathogenesis. In this review article, the role of ER and oxidative stress in DILI is thoroughly discussed. ,Hanghang Wu ... Francisco Javier Cubero [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [20] => Array ( [ArticleId] => 628 [Create_Time] => 2023-06-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630022414.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100521/100521.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100521/100521.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100521/100521_cover.png [JournalsId] => 6 [Title] => An analysis on the clinical features and risk factors associated with the prognosis of patients with drug-induced liver injury [Abstract] => Aim: This is a Chinese population-based study aimed to determine the causes and clinical features of drug-induced liver injury (DILI) from traditional Chinese medicines (TCMs) and current Western m [AbstractComplete] =>This is a Chinese population-based study aimed to determine the causes and clinical features of drug-induced liver injury (DILI) from traditional Chinese medicines (TCMs) and current Western medicines (WMs) and identify the risk factors of drug-induced liver failure (DILF) and chronic DILI for early recognition and better management.
The medical records of patients who were diagnosed with DILI for at least six-month follow-up between January 2018 to December 2020 were reviewed and investigated. The risk factors of DILF and chronic DILI were identified by univariate and multivariate logistic regression analysis.
TCMs (47.5%) including herbal medicine (83.0% in TCM-induced DILI) and some Chinese patent drugs were the leading cause of DILI in the present study. Cholestatic type was more associated with severe and chronic DILI. Pre-existing gallbladder disease, initial total bilirubin (TBIL), initial prothrombin time (PT), initial antinuclear antibodies (ANA), and clinical classification are independent risk factors for DILF. Prolonged T0.5AST and T0.5GGT were independent risk factors for chronic DILI [area under the curve (AUC) = 0.812, 95% confidence interval (CI): 0.748–0.876, P < 0.001] with cut-off values of 8.5 days and 29.5 days, respectively.
TCMs especially herbal medicine were the leading causes of DILI, and the risk of developing severe DILI was associated with pre-existing gallbladder disease, clinical classification, initial TBIL, PT, and ANA. T0.5AST and T0.5GGT might serve as indicators for chronicity.
Excessive alcohol intake is still among the leading causes of chronic liver diseases. Epidemiological studies suggest that per capita consumption of alcohol from various alcohol beverages e.g., beer, wine, or spirits, differs markedly between different areas of the world. Studies further suggest that different alcoholic beverages may impact the development of alcohol-related liver diseases (ALD) differentially. Specifically, results of several more recent epidemiological studies suggest that consumption of wine and herein especially of red wine may be less harmful in relation to the development of liver diseases than the intake of hard spirits. Results of studies evaluating the effects of beer on the development of ALD in humans are rather contradictory. Here, results of studies assessing the impact of wine, beer, and spirits on the development of ALD as well as possible underlying mechanisms are summarized and discussed.
[Names] => Finn Jung ... Ina Bergheim [Doi] => 10.37349/edd.2023.00022 [Published] => June 30, 2023 [Viewed] => 811 [Downloaded] => 47 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00022 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 120 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:118–132 [Recommend] => 0 [Keywords] => Beer, wine, spirits, ethanol, resveratrol, hop [DetailTitle] => Nutrition, Intestinal Barrier and Metabolic Liver Disease [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/120 [Id] => 100522 [ris] => https://www.explorationpub.com/uploads/Article/A100522/f532ae1e0a5df156c762ca2475236cc8.ris [bib] => https://www.explorationpub.com/uploads/Article/A100522/a8301947c0c07f48860bee8b75258f27.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-26 [CitethisArticle] => Jung F, Sánchez V, Brandt A, Bergheim I. Alcohol-related liver disease: also a question of what you drink? Explor Dig Dis. 2023;2:118–32. https://doi.org/10.37349/edd.2023.00022 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-30 02:39:27 [Bib_Time] => 2023-06-30 02:39:27 [KeysWordContens] => Alcohol-related liver disease: also a question of what you drink?, Beer, wine, spirits, ethanol, resveratrol, hop, Excessive alcohol intake is still among the leading causes of chronic liver diseases. Epidemiological studies suggest that per capita consumption of alcohol from various alcohol beverages e.g., beer, wine, or spirits, differs markedly between different areas of the world. Studies further suggest that different alcoholic beverages may impact the development of alcohol-related liver diseases (ALD) differentially. Specifically, results of several more recent epidemiological studies suggest that consumption of wine and herein especially of red wine may be less harmful in relation to the development of liver diseases than the intake of hard spirits. Results of studies evaluating the effects of beer on the development of ALD in humans are rather contradictory. Here, results of studies assessing the impact of wine, beer, and spirits on the development of ALD as well as possible underlying mechanisms are summarized and discussed. ,Finn Jung ... Ina Bergheim [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [22] => Array ( [ArticleId] => 695 [Create_Time] => 2023-08-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230825032847.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100523/100523.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100523/100523.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100523/100523_cover.png [JournalsId] => 6 [Title] => Ultra-processed food consumption and the risk of non-alcoholic fatty liver disease—What are the proposed mechanisms? [Abstract] => A high consumption of ultra-processed food (UPF) is a hallmark of Western diets that has been related to increased risk of non-communicable diseases. As an underlying mechanism, UPF may promote non- [AbstractComplete] =>A high consumption of ultra-processed food (UPF) is a hallmark of Western diets that has been related to increased risk of non-communicable diseases. As an underlying mechanism, UPF may promote non-alcoholic fatty liver disease (NAFLD) which is a key driver of metabolic impairment with extra-hepatic manifestations like type 2 diabetes, cardiovascular disease, chronic kidney disease, and osteoporosis among others. The present review provides an overview of UPF properties that may promote NAFLD and are thus potential targets for reformulation of UPF. Such approaches should address improvements in the quality of carbohydrates and fat, changes in food texture that lower eating rate as well as ingredients that prevent excess caloric intake or avoid dysbiosis and leaky gut syndrome. Promising strategies are enrichment with fiber, prebiotics, phytochemicals, and protein with a concurrent reduction in glycemic load, energy density, saturated fatty acids (FA; SFA), emulsifiers, fructose, and non-caloric sweeteners. Future studies are needed to examine the interactive and protective effects of such modifications in the composition of UPF on prevention and treatment of NAFLD.
[Names] => Franziska A. Hägele ... Anja Bosy-Westphal [Doi] => 10.37349/edd.2023.00023 [Published] => August 24, 2023 [Viewed] => 552 [Downloaded] => 28 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00023 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 120 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:133–148 [Recommend] => 0 [Keywords] => Ultra-processed foods, non-alcoholic fatty liver disease, appetite control, energy balance, saturated fatty acids, glycemic load [DetailTitle] => Nutrition, Intestinal Barrier and Metabolic Liver Disease [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/120 [Id] => 100523 [ris] => https://www.explorationpub.com/uploads/Article/A100523/85861cad1d2a65aacadab954ab94beb1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100523/4eb62733387102511314f8ce751f2b36.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Hägele FA, Enderle J, Rimbach G, Bosy-Westphal A. Ultra-processed food consumption and the risk of non-alcoholic fatty liver disease—What are the proposed mechanisms? Explor Dig Dis. 2023;2:133–148. https://doi.org/10.37349/edd.2023.00023 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-22 02:32:35 [Bib_Time] => 2023-08-22 02:32:35 [KeysWordContens] => Ultra-processed food consumption and the risk of non-alcoholic fatty liver disease—What are the proposed mechanisms?, Ultra-processed foods, non-alcoholic fatty liver disease, appetite control, energy balance, saturated fatty acids, glycemic load, A high consumption of ultra-processed food (UPF) is a hallmark of Western diets that has been related to increased risk of non-communicable diseases. As an underlying mechanism, UPF may promote non-alcoholic fatty liver disease (NAFLD) which is a key driver of metabolic impairment with extra-hepatic manifestations like type 2 diabetes, cardiovascular disease, chronic kidney disease, and osteoporosis among others. The present review provides an overview of UPF properties that may promote NAFLD and are thus potential targets for reformulation of UPF. Such approaches should address improvements in the quality of carbohydrates and fat, changes in food texture that lower eating rate as well as ingredients that prevent excess caloric intake or avoid dysbiosis and leaky gut syndrome. Promising strategies are enrichment with fiber, prebiotics, phytochemicals, and protein with a concurrent reduction in glycemic load, energy density, saturated fatty acids (FA; SFA), emulsifiers, fructose, and non-caloric sweeteners. Future studies are needed to examine the interactive and protective effects of such modifications in the composition of UPF on prevention and treatment of NAFLD. ,Franziska A. Hägele ... Anja Bosy-Westphal [PublishedText] => Published [IsEdit] => 0 [AccountId] => 46 [Zh] => 1 ) [23] => Array ( [ArticleId] => 716 [Create_Time] => 2023-08-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230908063230.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100524/100524.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100524/100524.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100524/100524_cover.png [JournalsId] => 6 [Title] => Pathophysiology of biochemical signs of primary biliary cholangitis [Abstract] => Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a rare chronic autoimmune cholestatic liver disease, affecting mostly females. With PBС develops chronic cholang [AbstractComplete] =>Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a rare chronic autoimmune cholestatic liver disease, affecting mostly females. With PBС develops chronic cholangiopathy, this is accompanied by the development of gradually progressive liver fibrosis, which leads to intrahepatic cholestasis. Defects in autoimmune tolerance are critical factors in the emergence of the disease. Biochemical signs in PBС appear already in the asymptomatic stage of the disease and they are associated with a disturbance of the secretion of bile acids. Understanding the pathophysiological mechanisms of these signs is essential to both the early diagnosis and treatment of PBC. Early diagnosis of the disease contributes to its more effective treatment. There are many scientifically based modern data on the pathophysiology of clinical and laboratory signs developing in PBС. The purpose of this review is to summarize the data available in the literature and those obtained by the authors on the mechanisms for the development of biochemical criteria for PBC and their diagnostic significance. The opportunity to present the pathophysiological mechanisms of the development of biochemical signs in patients with PBC is associated with the success in the development of modern research methods in biochemistry, molecular biology, and genetics.
[Names] => Vasiliy Ivanovich Reshetnyak, Igor Veniaminovich Maev [Doi] => 10.37349/edd.2023.00024 [Published] => August 27, 2023 [Viewed] => 608 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00024 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:149–171 [Recommend] => 0 [Keywords] => Primary biliary cholangitis (PBC), cholestasis, biochemical signs of PBC, alkaline phosphatase (AP), γ-glutamyl transferase (γ-GT), 5’-nucleotidase, disorders of lipid metabolism [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100524 [ris] => https://www.explorationpub.com/uploads/Article/A100524/50edb18d62be10a3efe2d7498adba42f.ris [bib] => https://www.explorationpub.com/uploads/Article/A100524/09619a309af1b037b45b3fb960631cba.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Reshetnyak VI, Maev IV. Pathophysiology of biochemical signs of primary biliary cholangitis. Explor Dig Dis. 2023;2:149–71. https://doi.org/10.37349/edd.2023.00024 [Jindex] => 0 [CName] => Vasiliy IvanovichReshetnyak, [CEmail] => vasiliy.reshetnyak@yandex.ru, [Ris_Time] => 2023-08-24 07:59:07 [Bib_Time] => 2023-08-24 07:59:07 [KeysWordContens] => Pathophysiology of biochemical signs of primary biliary cholangitis, Primary biliary cholangitis (PBC), cholestasis, biochemical signs of PBC, alkaline phosphatase (AP), γ-glutamyl transferase (γ-GT), 5’-nucleotidase, disorders of lipid metabolism, Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a rare chronic autoimmune cholestatic liver disease, affecting mostly females. With PBС develops chronic cholangiopathy, this is accompanied by the development of gradually progressive liver fibrosis, which leads to intrahepatic cholestasis. Defects in autoimmune tolerance are critical factors in the emergence of the disease. Biochemical signs in PBС appear already in the asymptomatic stage of the disease and they are associated with a disturbance of the secretion of bile acids. Understanding the pathophysiological mechanisms of these signs is essential to both the early diagnosis and treatment of PBC. Early diagnosis of the disease contributes to its more effective treatment. There are many scientifically based modern data on the pathophysiology of clinical and laboratory signs developing in PBС. The purpose of this review is to summarize the data available in the literature and those obtained by the authors on the mechanisms for the development of biochemical criteria for PBC and their diagnostic significance. The opportunity to present the pathophysiological mechanisms of the development of biochemical signs in patients with PBC is associated with the success in the development of modern research methods in biochemistry, molecular biology, and genetics. ,Vasiliy Ivanovich Reshetnyak, Igor Veniaminovich Maev [PublishedText] => Published [IsEdit] => 0 [AccountId] => 45 [Zh] => 1 ) [24] => Array ( [ArticleId] => 734 [Create_Time] => 2023-08-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901011442.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100525/100525.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100525/100525.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100525/edd-02-100525_cover.png [JournalsId] => 6 [Title] => Human liver stem cell-derived extracellular vesicles modulate long non-coding RNA expression profile in an in vivo model of non-alcoholic steatohepatitis [Abstract] => Aim: Modifications in long non-coding RNA (lncRNA) expression are associated with inflammation and fibrosis in chronic liver diseases. It has been recently demonstrated that human liver stem cell [AbstractComplete] =>Modifications in long non-coding RNA (lncRNA) expression are associated with inflammation and fibrosis in chronic liver diseases. It has been recently demonstrated that human liver stem cells (HLSCs) and their extracellular vesicles (EVs) can effectively reduce inflammation and fibrosis in a murine model of non-alcoholic steatohepatitis (NASH). Now it has been evaluated whether EVs can modify the expression of inflammation-related lncRNAs in NASH liver.
To induce NASH, severe combined immunodeficient mice were fed with a methionine-choline-deficient diet for 4 weeks. After 2 weeks of diet, 2.5 × 109 EVs were intravenously injected twice a week. An array of 84 inflammation-related lncRNAs was performed on the RNA isolated from NASH livers, and the expression of 14 selected lncRNAs was then validated by real-time polymerase chain reaction (PCR) analysis. Expression levels of maternally expressed gene 3 (Meg3) were further evaluated in vitro, in an activated human hepatic immortalized stellate cell line (LX-2) stimulated with EVs.
The screening showed an altered lncRNA expression profile in the liver of NASH mice, in respect to control healthy mice. EV treatment modulated several inflammation-related lncRNAs in NASH livers. Real-time PCR validation of array results indicated that EVs restored to normal levels the expression of 10 lncRNAs altered in NASH. In particular, EV stimulation reduced Meg3 expression levels, which were increased in NASH as well as in activated LX-2.
HLSC-EVs regulate the expression of inflammation-related lncRNAs impaired in NASH livers and in an in vitro model of liver fibrosis.
Nonalcoholic fatty liver disease (NAFLD) is an umbrella definition that describes the ectopic deposition of fat within the liver that occurs in the absence of inciting factors other than the metabolic syndrome and its individual features. NAFLD has a multi-factorial pathogenesis which determines heterogeneous clinical phenotypes and variable natural course spanning from liver-related (steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma) to extrahepatic outcomes (cardio-metabolic and cancer). This narrative review article leverages the key aspects of disease natural history as the background information to discuss studies that may inform strategies to risk-stratify NAFLD patients. Evaluation of hepatic fibrosis with non-invasive tools, including blood-based biomarkers and imaging-based elastometry techniques, seemingly retains the core information useful to predict the heterogeneous outcomes listed above. Additionally, genetic testing and metabolomic profiles may also be utilized to this end. In conclusion, a comprehensive understanding of the variable hepatic, cardio-metabolic and cancer outcomes of NAFLD may enable physicians and researchers to risk-stratify and accurately identify the multilayered prognosis of NAFLD individuals while also defining homogeneous patient subsets to enroll in clinical trials.
[Names] => Amedeo Lonardo [Doi] => 10.37349/edd.2023.00026 [Published] => August 30, 2023 [Viewed] => 815 [Downloaded] => 35 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00026 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 183 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:188–201 [Recommend] => 0 [Keywords] => Cardiovascular risk, cancer, chronic kidney disease, cirrhosis, fibrosis, nonalcoholic steatohepatitis [DetailTitle] => Advances in Hepato-gastroenterology: Diagnosis, Prognostication, and Disease Stratification [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/183 [Id] => 100526 [ris] => https://www.explorationpub.com/uploads/Article/A100526/61e524126687c8a6a7b58a540840412b.ris [bib] => https://www.explorationpub.com/uploads/Article/A100526/3fb5822d1ff12c684df259be9fb2ece5.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-26 [CitethisArticle] => Lonardo A. Principles of risk stratification in nonalcoholic fatty liver disease. A narrative review emphasizing non-invasive strategies. Explor Dig Dis. 2023;2:188–201. https://doi.org/10.37349/edd.2023.00026 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-29 03:13:34 [Bib_Time] => 2023-08-29 03:13:34 [KeysWordContens] => Principles of risk stratification in nonalcoholic fatty liver disease. A narrative review emphasizing non-invasive strategies, Cardiovascular risk, cancer, chronic kidney disease, cirrhosis, fibrosis, nonalcoholic steatohepatitis, Nonalcoholic fatty liver disease (NAFLD) is an umbrella definition that describes the ectopic deposition of fat within the liver that occurs in the absence of inciting factors other than the metabolic syndrome and its individual features. NAFLD has a multi-factorial pathogenesis which determines heterogeneous clinical phenotypes and variable natural course spanning from liver-related (steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma) to extrahepatic outcomes (cardio-metabolic and cancer). This narrative review article leverages the key aspects of disease natural history as the background information to discuss studies that may inform strategies to risk-stratify NAFLD patients. Evaluation of hepatic fibrosis with non-invasive tools, including blood-based biomarkers and imaging-based elastometry techniques, seemingly retains the core information useful to predict the heterogeneous outcomes listed above. Additionally, genetic testing and metabolomic profiles may also be utilized to this end. In conclusion, a comprehensive understanding of the variable hepatic, cardio-metabolic and cancer outcomes of NAFLD may enable physicians and researchers to risk-stratify and accurately identify the multilayered prognosis of NAFLD individuals while also defining homogeneous patient subsets to enroll in clinical trials. ,Amedeo Lonardo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 45 [Zh] => 1 ) [26] => Array ( [ArticleId] => 807 [Create_Time] => 2023-09-18 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031062606.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100527/100527.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100527/100527.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100527/100527_cover.png [JournalsId] => 6 [Title] => Drug-induced cholestasis: causative agents and challenges in diagnosis and management [Abstract] => Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominan [AbstractComplete] =>Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominantly hepatocellular, a non-negligible percentage of patients who present with cholestatic damage. Mixed damage is typically lumped together with cholestatic damage in the literature. Drug-induced cholestasis is often caused by the use of some non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (i.e., amoxicillin-clavulanic acid), statins, and anabolic agents, among others. Drug-associated cholestasis tends to have a more chronic course and mostly affects older population. There is also a genetic predisposition to toxic cholestasis caused by some drugs (amoxicillin-clavulanic acid, statins, etc.). Recently, anatomical alterations of the biliary tract induced by drugs (especially immunotherapy drugs) have been described. Bile duct injury is one of the histopathological findings that have prognostic significance in DILI. A correct differential diagnosis with other causes of cholestasis is mandatory to reach an accurate diagnosis. Ursodexycholic acid, corticosteroids, and replacement therapies have been used as a therapeutic arsenal, although more evidence is needed to establish them as a routine therapeutic management in clinical practice. The breakthrough and validation of biomarkers of cholestasis and bile duct injury is an urgent need for drug development and post-marketing phase.
[Names] => Jose M. Pinazo-Bandera ... Miren García-Cortés [Doi] => 10.37349/edd.2023.00027 [Published] => September 18, 2023 [Viewed] => 958 [Downloaded] => 46 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00027 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:202–222 [Recommend] => 0 [Keywords] => Cholestatic drug-induced liver injury, hepatotoxicity, drug-induced cholestasis [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100527 [ris] => https://www.explorationpub.com/uploads/Article/A100527/f84255adc911b9d5ea756caf23c30769.ris [bib] => https://www.explorationpub.com/uploads/Article/A100527/c087b6b1156a0159090b09e233b8e6cc.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Pinazo-Bandera JM, Toro-Ortiz JP, Andrade RJ, García-Cortés M. Drug-induced cholestasis: causative agents and challenges in diagnosis and management. Explor Dig Dis. 2023;2:202–22. https://doi.org/10.37349/edd.2023.00027 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-31 06:26:06 [Bib_Time] => 2023-10-31 06:26:06 [KeysWordContens] => Drug-induced cholestasis: causative agents and challenges in diagnosis and management, Cholestatic drug-induced liver injury, hepatotoxicity, drug-induced cholestasis, Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominantly hepatocellular, a non-negligible percentage of patients who present with cholestatic damage. Mixed damage is typically lumped together with cholestatic damage in the literature. Drug-induced cholestasis is often caused by the use of some non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (i.e., amoxicillin-clavulanic acid), statins, and anabolic agents, among others. Drug-associated cholestasis tends to have a more chronic course and mostly affects older population. There is also a genetic predisposition to toxic cholestasis caused by some drugs (amoxicillin-clavulanic acid, statins, etc.). Recently, anatomical alterations of the biliary tract induced by drugs (especially immunotherapy drugs) have been described. Bile duct injury is one of the histopathological findings that have prognostic significance in DILI. A correct differential diagnosis with other causes of cholestasis is mandatory to reach an accurate diagnosis. Ursodexycholic acid, corticosteroids, and replacement therapies have been used as a therapeutic arsenal, although more evidence is needed to establish them as a routine therapeutic management in clinical practice. The breakthrough and validation of biomarkers of cholestasis and bile duct injury is an urgent need for drug development and post-marketing phase. ,Jose M. Pinazo-Bandera ... Miren García-Cortés [PublishedText] => Published [IsEdit] => 0 [AccountId] => 80 [Zh] => 1 ) [27] => Array ( [ArticleId] => 844 [Create_Time] => 2023-10-16 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031062941.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100528/100528.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100528/100528.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100528/100528_cover.png [JournalsId] => 6 [Title] => Interplay of autophagy, apoptosis, and senescence in primary biliary cholangitis [Abstract] => The pathogenesis of primary biliary cholangitis (PBC) is particularly complicated as both intrinsic and extrinsic factors are implicated. Several forms of cellular death, both programmable and non-p [AbstractComplete] =>The pathogenesis of primary biliary cholangitis (PBC) is particularly complicated as both intrinsic and extrinsic factors are implicated. Several forms of cellular death, both programmable and non-programmable, operate leading biliary epithelial cells (BECs) to elimination. The precise role of critical pathways like autophagy, apoptosis, senescence, and their interplay has not been fully clarified. Therefore, in this review, data on these important mechanisms are presented and their implication in PBC is discussed. The interplay of the three mechanisms is examined and the factors that drive them are analyzed. Moreover, the upstream drivers of autophagy, apoptosis, and senescence are presented. They include the loss of the protective bicarbonate umbrella in BECs due to the reduction of activity of the anion exchanger 2 (AE2) with the resultant activation of the intracellular soluble adenylyl cyclase (sAC). The role of toxic bile acids is also presented. A sequence of events is proposed including involvement of the gut-liver axis and the possible role of ferroptosis. Finally, a brief account of the initial trigger of the disease is given.
[Names] => Elias Kouroumalis ... Argyro Voumvouraki [Doi] => 10.37349/edd.2023.00028 [Published] => October 16, 2023 [Viewed] => 525 [Downloaded] => 17 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00028 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 71 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:223–245 [Recommend] => 0 [Keywords] => Primary biliary cholangitis, autophagy, apoptosis, senescence, mitophagy [DetailTitle] => CHOLESTASIS [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/71 [Id] => 100528 [ris] => https://www.explorationpub.com/uploads/Article/A100528/59d0ba3af17fe89f94de661c8b5b0f43.ris [bib] => https://www.explorationpub.com/uploads/Article/A100528/daf856b02e5b6be791cc44159d2a36c4.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kouroumalis E, Tsomidis I, Voumvouraki A. Interplay of autophagy, apoptosis, and senescence in primary biliary cholangitis. Explor Dig Dis. 2023;2:223–45. https://doi.org/10.37349/edd.2023.00028 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-31 06:29:42 [Bib_Time] => 2023-10-31 06:29:42 [KeysWordContens] => Interplay of autophagy, apoptosis, and senescence in primary biliary cholangitis, Primary biliary cholangitis, autophagy, apoptosis, senescence, mitophagy, The pathogenesis of primary biliary cholangitis (PBC) is particularly complicated as both intrinsic and extrinsic factors are implicated. Several forms of cellular death, both programmable and non-programmable, operate leading biliary epithelial cells (BECs) to elimination. The precise role of critical pathways like autophagy, apoptosis, senescence, and their interplay has not been fully clarified. Therefore, in this review, data on these important mechanisms are presented and their implication in PBC is discussed. The interplay of the three mechanisms is examined and the factors that drive them are analyzed. Moreover, the upstream drivers of autophagy, apoptosis, and senescence are presented. They include the loss of the protective bicarbonate umbrella in BECs due to the reduction of activity of the anion exchanger 2 (AE2) with the resultant activation of the intracellular soluble adenylyl cyclase (sAC). The role of toxic bile acids is also presented. A sequence of events is proposed including involvement of the gut-liver axis and the possible role of ferroptosis. Finally, a brief account of the initial trigger of the disease is given. ,Elias Kouroumalis ... Argyro Voumvouraki [PublishedText] => Published [IsEdit] => 0 [AccountId] => 80 [Zh] => 1 ) [28] => Array ( [ArticleId] => 858 [Create_Time] => 2023-10-26 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031073307.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100529/100529.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100529/100529.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100529/100529_cover.png [JournalsId] => 6 [Title] => Molecular mechanisms of metabolic disease-associated hepatic inflammation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis [Abstract] => Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, [AbstractComplete] =>Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD/NASH is a comorbidity of many metabolic disorders such as obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and chronic kidney disease. These metabolic diseases are often accompanied by systemic or extrahepatic inflammation, which plays an important role in the pathogenesis and treatment of NAFLD or NASH. Metabolites, such as short-chain fatty acids, impact the function, inflammation, and death of hepatocytes, the primary parenchymal cells in the liver tissue. Cholangiocytes, the epithelial cells that line the bile ducts, can differentiate into proliferative hepatocytes in chronic liver injury. In addition, hepatic non-parenchymal cells, including liver sinusoidal endothelial cells, hepatic stellate cells, and innate and adaptive immune cells, are involved in liver inflammation. Proteins such as fibroblast growth factors, acetyl-coenzyme A carboxylases, and nuclear factor erythroid 2-related factor 2 are involved in liver metabolism and inflammation, which are potential targets for NASH treatment. This review focuses on the effects of metabolic disease-induced extrahepatic inflammation, liver inflammation, and the cellular and molecular mechanisms of liver metabolism on the development and progression of NAFLD and NASH, as well as the associated treatments.
[Names] => Chunye Zhang ... Ming Yang [Doi] => 10.37349/edd.2023.00029 [Published] => October 25, 2023 [Viewed] => 968 [Downloaded] => 35 [Subject] => Review [Year] => 2023 [CiteUrl] => https://doi.org/10.37349/edd.2023.00029 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 202 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:246–275 [Recommend] => 0 [Keywords] => Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolites, inflammation, hepatocyte death, molecular targets, clinical trials [DetailTitle] => Cellular and Molecular Targets for NAFLD or MAFLD Treatments and Their Functions in Liver Fibrosis, Cirrhosis, and Cancer [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/202 [Id] => 100529 [ris] => https://www.explorationpub.com/uploads/Article/A100529/c497e2626c8618a33e7e363e643fad54.ris [bib] => https://www.explorationpub.com/uploads/Article/A100529/78b114a3b1cb6cf501ad70c836dbd53c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Zhang C, Sui Y, Liu S, Yang M. Molecular mechanisms of metabolic disease-associated hepatic inflammation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Explor Dig Dis. 2023;2:246–75. https://doi.org/10.37349/edd.2023.00029 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-31 07:33:07 [Bib_Time] => 2023-10-31 07:33:07 [KeysWordContens] => Molecular mechanisms of metabolic disease-associated hepatic inflammation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolites, inflammation, hepatocyte death, molecular targets, clinical trials, Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD/NASH is a comorbidity of many metabolic disorders such as obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and chronic kidney disease. These metabolic diseases are often accompanied by systemic or extrahepatic inflammation, which plays an important role in the pathogenesis and treatment of NAFLD or NASH. Metabolites, such as short-chain fatty acids, impact the function, inflammation, and death of hepatocytes, the primary parenchymal cells in the liver tissue. Cholangiocytes, the epithelial cells that line the bile ducts, can differentiate into proliferative hepatocytes in chronic liver injury. In addition, hepatic non-parenchymal cells, including liver sinusoidal endothelial cells, hepatic stellate cells, and innate and adaptive immune cells, are involved in liver inflammation. Proteins such as fibroblast growth factors, acetyl-coenzyme A carboxylases, and nuclear factor erythroid 2-related factor 2 are involved in liver metabolism and inflammation, which are potential targets for NASH treatment. This review focuses on the effects of metabolic disease-induced extrahepatic inflammation, liver inflammation, and the cellular and molecular mechanisms of liver metabolism on the development and progression of NAFLD and NASH, as well as the associated treatments. ,Chunye Zhang ... Ming Yang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 85 [Zh] => 1 ) [29] => Array ( [ArticleId] => 868 [Create_Time] => 2023-10-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202401/20240112023951.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100530/100530.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100530/100530.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100530/100530_cover.png [JournalsId] => 6 [Title] => Familial achalasia isolated or syndromic: about 18 families [Abstract] => Aim: Familial achalasia (FA) is a very rare condition. This work aims to evaluate its prevalence, characterize its clinical profile in a large series, and assess the efficacy and safety of pneuma [AbstractComplete] =>Familial achalasia (FA) is a very rare condition. This work aims to evaluate its prevalence, characterize its clinical profile in a large series, and assess the efficacy and safety of pneumatic dilation (PD) in this context.
A total of 817 patients with achalasia were collected over a period of 20 years (1990–2010). All cases of FA: isolated or associated to Allgrove syndrome, were looked for in both parents and siblings.
In this study, 18 families with FA were identified n = 41 patients (5%). Two members were affected in each family, in 14 families, three members per family in three others, and for the remaining family 04 members. All cases of achalasia were observed in siblings and parent to child transmission was unfound. Achalasia was associated to Allgrove syndrome in 15 families. It was isolated in 3 families. Consanguinity was found in 89% of patients, and death at a young age in the siblings was recorded in 27% of cases. Achalasia was present before the age of 5 years in 75% of cases. There was no difference between the two groups for age, age at onset, sex and the presence of the cardinal signs of achalasia. A total of 102 dilations were performed. Only one session in 31% of cases, two in 38%, three in 17% and more than three sessions in 14%. The long-term success rate of PD was low.
FA manifests almost exclusively in childhood. It is rarely isolated; most often falls under Allgrove syndrome. Alacrima is the earliest sign that should lead to the diagnosis. The long-term success rate of PD is rather low. This requires recourse to multiple sessions of PD or Heller’s cardiomyotomy which may be the best initial approach.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases. Over time, there has been a significant increase in the prevalence of MASLD. It has become one of the leading causes of hepatocellular carcinoma (HCC) in the United States, France, and the United Kingdom. Globally, the incidence of HCC related to MASLD may further increase with the growing prevalence of obesity. Non-alcoholic steatohepatitis (NASH) is an important stage of MASLD, which is more likely to cause cirrhosis and even HCC. And patients with NASH cirrhosis have a much higher incidence of hepatocellular cancer than patients with non-cirrhotic MASLD. As a result, it is critical to investigate the targets of MASLD therapy in HCC. This article reviews therapeutic targets of MASLD, such as farnesoid X receptor (FXR), peroxisome proliferator activated receptor (PPAR), fibroblast growth factor-21 (FGF-21), etc., and introduces the drugs related to these targets and their mechanisms of action in HCC. In addition, the developmental process and pathogenesis of MASLD, as well as risk factors for HCC development, are discussed. These are of great significance for the prevention and treatment of HCC.
[Names] => Chenyu Wei ... Xianguang Yang [Doi] => 10.37349/edd.2023.00031 [Published] => December 13, 2023 [Viewed] => 681 [Downloaded] => 21 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00031 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 202 [TitleAbbr] => Explor Dig Dis. [Pages] => 2023;2:282–296 [Recommend] => 0 [Keywords] => Metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma, farnesoid X receptor, peroxisome proliferator activated receptor, fibroblast growth factor-21 [DetailTitle] => Cellular and Molecular Targets for NAFLD or MAFLD Treatments and Their Functions in Liver Fibrosis, Cirrhosis, and Cancer [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/202 [Id] => 100531 [ris] => https://www.explorationpub.com/uploads/Article/A100531/e3e3c98888bb55caf81c5f10b7ef41be.ris [bib] => https://www.explorationpub.com/uploads/Article/A100531/454a35c6430a29432596ad77e0add42a.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Wei C, Wu J, Zhang C, Zhao Y, Li C, Yang X. Therapeutic targets for metabolic dysfunction-associated steatotic liver disease and their roles in hepatocellular carcinoma. Explor Dig Dis. 2023;2:282–96. https://doi.org/10.37349/edd.2023.00031 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-13 01:39:01 [Bib_Time] => 2023-12-13 06:13:54 [KeysWordContens] => Therapeutic targets for metabolic dysfunction-associated steatotic liver disease and their roles in hepatocellular carcinoma, Metabolic dysfunction-associated steatotic liver disease, hepatocellular carcinoma, farnesoid X receptor, peroxisome proliferator activated receptor, fibroblast growth factor-21, Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases. Over time, there has been a significant increase in the prevalence of MASLD. It has become one of the leading causes of hepatocellular carcinoma (HCC) in the United States, France, and the United Kingdom. Globally, the incidence of HCC related to MASLD may further increase with the growing prevalence of obesity. Non-alcoholic steatohepatitis (NASH) is an important stage of MASLD, which is more likely to cause cirrhosis and even HCC. And patients with NASH cirrhosis have a much higher incidence of hepatocellular cancer than patients with non-cirrhotic MASLD. As a result, it is critical to investigate the targets of MASLD therapy in HCC. This article reviews therapeutic targets of MASLD, such as farnesoid X receptor (FXR), peroxisome proliferator activated receptor (PPAR), fibroblast growth factor-21 (FGF-21), etc., and introduces the drugs related to these targets and their mechanisms of action in HCC. In addition, the developmental process and pathogenesis of MASLD, as well as risk factors for HCC development, are discussed. These are of great significance for the prevention and treatment of HCC. ,Chenyu Wei ... Xianguang Yang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 88 [Zh] => 1 ) [32] => Array ( [ArticleId] => 1024 [Create_Time] => 2023-12-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231225055440.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100532/100532.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100532/100532.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100532/100532_cover.png [JournalsId] => 6 [Title] => Impact of the direct acting antivirals on chronic hepatitis C prevalence on the Swiss organ transplantation list: a retrospective analysis [Abstract] => Aim: In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the [AbstractComplete] =>In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the yearly listed numbers of HCV RNA-positive (RNA+) patients and their mortality on the Swiss organ transplantation waiting list (SOWL).
In this retrospective secondary time series analysis of yearly aggregated data on listed and delisted patients from a subset of HCV RNA+ patients on the SOWL, listed patients were grouped by the requested organ, and delisted patients by reason. Time series were split into two periods of equal length, the phases before and after DAA implementation, and the mean difference was tested using the Mann-Whitney U test.
From 2008 to 2019, 328 HCV RNA+ patients were listed on SOWL, 86.6% requesting liver, 11.6% kidney, and 1.8% other organ transplantations. A total of 285 RNA+ patients were delisted from SOWL: 14.7% died, 75.4% had been transplanted, and 9.8% were delisted without surgery. There were significant reductions of patients listed for requesting any organ (–21.7, P = 0.004), liver (–18.3, P = 0.004), or kidney (–3.0, P = 0.031) comparing the periods before and after DAA launch. The mean number of delistings after transplantation (–11.2, P = 0.010), or death (–4, P < 0.001) show a significant reduction.
With DAAs, the rising trend of HCV RNA+ people waiting for organs was broken, as was the increasing trend of mortality on the SOWL among HCV RNA+ individuals.
This study aims to determine the significance of chronic hyperglycemia for the reduced efficacy of eradication therapy in patients with type 2 diabetes mellitus (T2DM) and Helicobacter pylori (H. pylori)-associated upper gastrointestinal tract pathology as well as for H. pylori survival.
A prospective randomized study with the participation of 180 patients (87 men and 93 women) with H. pylori-associated upper gastrointestinal pathology was carried out. Ninety of these patients were with T2DM and 90 were without diabetes mellitus (DM). The patients were divided into 4 groups of 45 patients: the group 1 included non-diabetic patients treated with the classical triple eradication scheme; the group 2 included patients with T2DM treated with the classical triple eradication scheme; the group 3 included non-diabetic patients treated with bismuth quadro-therapy; the group 4 included patients with T2DM treated with bismuth quadro-therapy. The presence of H. pylori and evaluation of eradication efficacy was carried out using the Helix breath test.
The effectiveness of 1st line anti-Helicobacter therapy was higher (88.2%) in patients without diabetes in comparison with the group of patients with concomitant T2DM (74.7%). The efficacy of classical triple eradication therapy in patients with concomitant T2DM was 69.1%, and quadro-therapy was 80.5%. There was significantly lower effectiveness (P < 0.017) of eradication therapy in patients with T2DM and glycated hemoglobin (HbA1c) level ≥ 7.0% as compared with the group of patients in whom the target (≤ 6.5%) level of HbA1c was achieved.
Chronic hyperglycemia has a favorable effect on the viability of H. pylori bacteria in patients with T2DM. A hypothesis explaining the reduced efficacy of eradication therapy in patients with hyperglycemia has been proposed.
Drug-induced liver injury (DILI) poses a complex and heterogeneous clinical challenge, which often resembles non-drug related acute or chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, certain drugs can induce hepatic steatosis, which is considered a rare variant of hepatotoxicity. Additionally, the detection and diagnosis of DILI in patients with non-alcoholic liver disease present additional challenges that require attention. The importance of achieving an accurate diagnosis is highlighted by the different therapeutic approaches needed for each of these diseases. Nonetheless, as definitive diagnostic tests and distinct biomarkers often remain elusive, the differential diagnosis must rely on a combination of clinical, biochemical, histological, and immunophenotypic profiling. The diagnosis of hepatotoxicity is predicated upon the temporal nexus between the administration of a potentially hepatotoxic drug and the onset of hepatic injury, concomitantly excluding alternative hepatic pathologies. More frequently, this condition presents an acute course, with a more pronounced elevation of cytolytic and cholestatic parameters as compared to fatty liver disease. Advances in elucidating the underlying mechanisms hold promise for bolstering the diagnosis and management of these conditions. This article aims to thoroughly examine and emphasize the currently available scientific evidence to provide valuable insights into the diagnostic strategies for DILI, metabolic-associated liver disease, and drug-induced steatosis (DIS).
[Names] => Miren García-Cortés ... Alberto García-García [Doi] => 10.37349/edd.2023.00034 [Published] => December 27, 2023 [Viewed] => 452 [Downloaded] => 20 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2023.00034 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 97 [TitleAbbr] => Explor Dig Dis [Pages] => 2023;2:318–336 [Recommend] => 0 [Keywords] => Drug-induced liver injury, metabolic dysfunction-associated steatotic liver disease, non-alcoholic fatty liver disease, drug-induced steatosis [DetailTitle] => Drug-induced Liver Injury: From Bench to Clinical Application [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/97 [Id] => 100534 [ris] => https://www.explorationpub.com/uploads/Article/A100534/c0337150779a611ace32375ba8293d6e.ris [bib] => https://www.explorationpub.com/uploads/Article/A100534/b011a4176b9d563bec144ae2e57ea02f.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => García-Cortés M, Toro-Ortiz JP, García-García A. Deciphering the liver enigma: distinguishing drug-induced liver injury and metabolic dysfunction-associated steatotic liver disease—a comprehensive narrative review. Explor Dig Dis. 2023;2:318–36. https://doi.org/10.37349/edd.2023.00034 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-26 06:51:46 [Bib_Time] => 2023-12-26 06:51:46 [KeysWordContens] => Deciphering the liver enigma: distinguishing drug-induced liver injury and metabolic dysfunction-associated steatotic liver disease—a comprehensive narrative review, Drug-induced liver injury, metabolic dysfunction-associated steatotic liver disease, non-alcoholic fatty liver disease, drug-induced steatosis, Drug-induced liver injury (DILI) poses a complex and heterogeneous clinical challenge, which often resembles non-drug related acute or chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, certain drugs can induce hepatic steatosis, which is considered a rare variant of hepatotoxicity. Additionally, the detection and diagnosis of DILI in patients with non-alcoholic liver disease present additional challenges that require attention. The importance of achieving an accurate diagnosis is highlighted by the different therapeutic approaches needed for each of these diseases. Nonetheless, as definitive diagnostic tests and distinct biomarkers often remain elusive, the differential diagnosis must rely on a combination of clinical, biochemical, histological, and immunophenotypic profiling. The diagnosis of hepatotoxicity is predicated upon the temporal nexus between the administration of a potentially hepatotoxic drug and the onset of hepatic injury, concomitantly excluding alternative hepatic pathologies. More frequently, this condition presents an acute course, with a more pronounced elevation of cytolytic and cholestatic parameters as compared to fatty liver disease. Advances in elucidating the underlying mechanisms hold promise for bolstering the diagnosis and management of these conditions. This article aims to thoroughly examine and emphasize the currently available scientific evidence to provide valuable insights into the diagnostic strategies for DILI, metabolic-associated liver disease, and drug-induced steatosis (DIS). ,Miren García-Cortés ... Alberto García-García [PublishedText] => Published [IsEdit] => 0 [AccountId] => 78 [Zh] => 1 ) [35] => Array ( [ArticleId] => 1078 [Create_Time] => 2024-01-18 [zipUrl] => https://www.explorationpub.com/uploads/zip/202401/20240117064148.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100536/100536.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100536/100536.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100536/100536_cover.png [JournalsId] => 6 [Title] => Precision medicine in chemotherapy: Is there room for advancement in colorectal cancer? [Abstract] => [AbstractComplete] => [Names] => Michele Ghidini [Doi] => 10.37349/edd.2024.00036 [Published] => January 18, 2024 [Viewed] => 246 [Downloaded] => 7 [Subject] => Editorial [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00036 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 186 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:2–4 [Recommend] => 0 [Keywords] => [DetailTitle] => Latest Updates in the Endoscopic, Surgical and Medical Treatment of Resectable and Advanced Gastrointestinal Cancers [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/186 [Id] => 100536 [ris] => https://www.explorationpub.com/uploads/Article/A100536/f3f2b5d0134df450bc9eaffc317b97fb.ris [bib] => https://www.explorationpub.com/uploads/Article/A100536/892acfc0c71dfa014125348eebd1b53c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ghidini M. Precision medicine in chemotherapy: Is there room for advancement in colorectal cancer? Explor Dig Dis. 2024;3:2–4. https://doi.org/10.37349/edd.2024.00036 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-17 06:41:48 [Bib_Time] => 2024-01-17 06:41:48 [KeysWordContens] => Precision medicine in chemotherapy: Is there room for advancement in colorectal cancer?,,,Michele Ghidini [PublishedText] => Published [IsEdit] => 0 [AccountId] => 79 [Zh] => 1 ) [36] => Array ( [ArticleId] => 1097 [Create_Time] => 2024-02-05 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229090839.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100537/100537.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100537/100537.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100537/edd-03-100537_cover.png [JournalsId] => 6 [Title] => Bile as a liquid biopsy matrix: potential applications and limitations [Abstract] => Hunting for tumoral material in body fluids, traditionally in blood, the so-called liquid biopsy is set to revolutionize the diagnosis and management of oncological patients. However, other biofluid [AbstractComplete] =>Hunting for tumoral material in body fluids, traditionally in blood, the so-called liquid biopsy is set to revolutionize the diagnosis and management of oncological patients. However, other biofluids can also be considered as alternative sources of biomarkers to provide clinically valuable information for multiple diseases. This is the case of bile, a fluid produced in the liver, stored in the gallbladder, and excreted to the duodenum, which complex composition is known to change in different pathological conditions. Remarkably, different works have demonstrated that the identification of mutations in bile cell-free DNA (cfDNA) can outperform blood analysis for the early diagnosis of biliopancreatic tumors causing biliary strictures. Here, the literature in which bile has been tested as a liquid biopsy matrix where lipids, metabolites, proteins, and cfDNA among other analytes were measured is reviewed. Moreover, the clinical situations and procedures where bile can be available, discussing the possible applications and limitations of bile analysis are summarized. The scientific relevance and clinical potential of bile harvesting, biobanking, and analysis are put forward. All this evidence supports the value of bile as a liquid biopsy matrix for the management of patients beyond cancer, and perhaps also beyond “blood, sweat, and tears”.
[Names] => Maria Arechederra ... Carmen Berasain [Doi] => 10.37349/edd.2024.00037 [Published] => February 04, 2024 [Viewed] => 326 [Downloaded] => 15 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00037 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:5–21 [Recommend] => 0 [Keywords] => Hepatopancreatobiliary tumors, diagnosis, biomarkers, bile collection, biliary disease, liquid biopsy [DetailTitle] => [DetailUrl] => [Id] => 100537 [ris] => https://www.explorationpub.com/uploads/Article/A100537/43a9f2b8a40f136b12695ebb7d2f2d84.ris [bib] => https://www.explorationpub.com/uploads/Article/A100537/511a507e57f533b51f8f2bb22332c67a.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Arechederra M, Rullán M, Oyón D, Ávila MA, Urman J, Berasain C. Bile as a liquid biopsy matrix: potential applications and limitations. Explor Dig Dis. 2024;3:5–21. https://doi.org/10.37349/edd.2024.00037 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-31 09:14:01 [Bib_Time] => 2024-01-31 09:14:01 [KeysWordContens] => Bile as a liquid biopsy matrix: potential applications and limitations, Hepatopancreatobiliary tumors, diagnosis, biomarkers, bile collection, biliary disease, liquid biopsy, Hunting for tumoral material in body fluids, traditionally in blood, the so-called liquid biopsy is set to revolutionize the diagnosis and management of oncological patients. However, other biofluids can also be considered as alternative sources of biomarkers to provide clinically valuable information for multiple diseases. This is the case of bile, a fluid produced in the liver, stored in the gallbladder, and excreted to the duodenum, which complex composition is known to change in different pathological conditions. Remarkably, different works have demonstrated that the identification of mutations in bile cell-free DNA (cfDNA) can outperform blood analysis for the early diagnosis of biliopancreatic tumors causing biliary strictures. Here, the literature in which bile has been tested as a liquid biopsy matrix where lipids, metabolites, proteins, and cfDNA among other analytes were measured is reviewed. Moreover, the clinical situations and procedures where bile can be available, discussing the possible applications and limitations of bile analysis are summarized. The scientific relevance and clinical potential of bile harvesting, biobanking, and analysis are put forward. All this evidence supports the value of bile as a liquid biopsy matrix for the management of patients beyond cancer, and perhaps also beyond “blood, sweat, and tears”. ,Maria Arechederra ... Carmen Berasain [PublishedText] => Published [IsEdit] => 0 [AccountId] => 24 [Zh] => 1 ) [37] => Array ( [ArticleId] => 1132 [Create_Time] => 2024-02-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240228071444.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100538/100538.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100538/100538.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100538/edd-03-100538_cover.png [JournalsId] => 6 [Title] => SERPINB3 in fibrogenic chronic liver diseases and primary liver cancers [Abstract] => Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to [AbstractComplete] =>Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to the development of primary liver cancers, represent a major burden for human health on a worldwide basis. Although the present knowledge on the pathogenesis of CLDs progression and primary liver cancers development has remarkably increased in the last decades, critical molecular mediators remain incompletely understood, and approved antifibrotic therapies to efficiently counteract CLDs progression and liver cancer are lacking. In the present review, this study will specifically analyse the putative contribution of SERPINB3, a member of the superfamily of serine-protease inhibitors (SERPINs), which has been shown to exert significant pro-inflammatory and pro-fibrogenic roles in progressive CLDs as well as to be involved in the development of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and hepatoblastoma.
[Names] => Patrizia Pontisso, Maurizio Parola [Doi] => 10.37349/edd.2024.00038 [Published] => February 28, 2024 [Viewed] => 211 [Downloaded] => 10 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00038 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 161 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:22–41 [Recommend] => 0 [Keywords] => SERPINB3, liver fibrosis, hepatitis, cirrhosis, hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma [DetailTitle] => Fibrosis and Hepatobiliary Cancer [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/161 [Id] => 100538 [ris] => https://www.explorationpub.com/uploads/Article/A100538/4e3197ed9c89f6b65c648329f11ce788.ris [bib] => https://www.explorationpub.com/uploads/Article/A100538/8c820c1137a5b65a48cf6f3eadf4373a.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Pontisso P, Parola M. SERPINB3 in fibrogenic chronic liver diseases and primary liver cancers. Explor Dig Dis. 2024;3:22–41. https://doi.org/10.37349/edd.2024.00038 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-28 01:58:11 [Bib_Time] => 2024-02-28 01:58:11 [KeysWordContens] => SERPINB3 in fibrogenic chronic liver diseases and primary liver cancers, SERPINB3, liver fibrosis, hepatitis, cirrhosis, hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma, Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to the development of primary liver cancers, represent a major burden for human health on a worldwide basis. Although the present knowledge on the pathogenesis of CLDs progression and primary liver cancers development has remarkably increased in the last decades, critical molecular mediators remain incompletely understood, and approved antifibrotic therapies to efficiently counteract CLDs progression and liver cancer are lacking. In the present review, this study will specifically analyse the putative contribution of SERPINB3, a member of the superfamily of serine-protease inhibitors (SERPINs), which has been shown to exert significant pro-inflammatory and pro-fibrogenic roles in progressive CLDs as well as to be involved in the development of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and hepatoblastoma. ,Patrizia Pontisso, Maurizio Parola [PublishedText] => Published [IsEdit] => 0 [AccountId] => 24 [Zh] => 1 ) [38] => Array ( [ArticleId] => 1134 [Create_Time] => 2024-02-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229052026.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100539/100539.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100539/100539.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100539/100539_cover.png [JournalsId] => 6 [Title] => The central role of mitochondrial metabolism in hepatic steatosis [Abstract] => Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways fo [AbstractComplete] =>Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.
[Names] => Sanda Win ... Filbert Win Min Aung [Doi] => 10.37349/edd.2024.00039 [Published] => February 29, 2024 [Viewed] => 471 [Downloaded] => 20 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00039 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 196 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:42–68 [Recommend] => 0 [Keywords] => Tricarboxylic acid cycle (TCA cycle), citric acid, acetyl-CoA, SH3 domain-binding protein 5 (SAB/SH3BP5), c-Jun N-terminal kinase (JNK), metabolic adaptation, lipogenesis [DetailTitle] => Mitochondria and Lipid Signalling in Liver Diseases [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/196 [Id] => 100539 [ris] => https://www.explorationpub.com/uploads/Article/A100539/eaa2adb3d8b764a1303cc9b089939f37.ris [bib] => https://www.explorationpub.com/uploads/Article/A100539/1f6589931435ecb31534410f657a11cb.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Win S, Than TA, Kaplowitz N, Wong N, Arya A, Win ZT, et al. The central role of mitochondrial metabolism in hepatic steatosis. Explor Dig Dis. 2024;3:42–68. https://doi.org/10.37349/edd.2024.00039 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-23 01:52:35 [Bib_Time] => 2024-02-23 01:52:35 [KeysWordContens] => The central role of mitochondrial metabolism in hepatic steatosis, Tricarboxylic acid cycle (TCA cycle), citric acid, acetyl-CoA, SH3 domain-binding protein 5 (SAB/SH3BP5), c-Jun N-terminal kinase (JNK), metabolic adaptation, lipogenesis, Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis. ,Sanda Win ... Filbert Win Min Aung [PublishedText] => Published [IsEdit] => 0 [AccountId] => 69 [Zh] => 1 ) [39] => Array ( [ArticleId] => 1180 [Create_Time] => 2024-03-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202403/20240322024450.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100540/100540.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100540/100540.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100540/100540_cover.png [JournalsId] => 6 [Title] => Liver metastatic colonization by invasive cancer cells: a review of potential biomarkers with mitochondrial involvement [Abstract] => The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The [AbstractComplete] =>The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases.
[Names] => Daniel L. Pouliquen [Doi] => 10.37349/edd.2024.00040 [Published] => March 22, 2024 [Viewed] => 168 [Downloaded] => 8 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00040 [Inline] => 1 [Type] => 0 [Issue] => 2 [Topic] => 196 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:69–85 [Recommend] => 0 [Keywords] => Cancer, liver metastasis, mitochondrial biomarkers, metabolic reprogramming, liver metabolism, lipid metabolism, proteomics, malignant peritoneal mesothelioma [DetailTitle] => Mitochondria and Lipid Signalling in Liver Diseases [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/196 [Id] => 100540 [ris] => https://www.explorationpub.com/uploads/Article/A100540/e9bccfe407f0fcba49336b2069536ef9.ris [bib] => https://www.explorationpub.com/uploads/Article/A100540/e7b4bff7afdec3469fab53a221b69652.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Pouliquen DL. Liver metastatic colonization by invasive cancer cells: a review of potential biomarkers with mitochondrial involvement. Explor Dig Dis. 2024;3:69–85. https://doi.org/10.37349/edd.2024.00040 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-03-18 07:23:04 [Bib_Time] => 2024-03-18 07:23:04 [KeysWordContens] => Liver metastatic colonization by invasive cancer cells: a review of potential biomarkers with mitochondrial involvement, Cancer, liver metastasis, mitochondrial biomarkers, metabolic reprogramming, liver metabolism, lipid metabolism, proteomics, malignant peritoneal mesothelioma, The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases. ,Daniel L. Pouliquen [PublishedText] => Published [IsEdit] => 0 [AccountId] => 69 [Zh] => 1 ) [40] => Array ( [ArticleId] => 1194 [Create_Time] => 2024-03-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202403/20240329064012.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100541/100541.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100541/100541.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100541/100541_cover.png [JournalsId] => 6 [Title] => Remarkable alpha-fetoprotein elevation and pseudo-infarction of cirrhotic liver: case report [Abstract] => This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude h [AbstractComplete] =>This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction.
[Names] => Maged Tharwat Elghannam ... Mohammed Darwish ELTalkawy [Doi] => 10.37349/edd.2024.00041 [Published] => March 29, 2024 [Viewed] => 115 [Downloaded] => 5 [Subject] => Case Report [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00041 [Inline] => 1 [Type] => 0 [Issue] => 0 [Topic] => 0 [TitleAbbr] => Explor Dig Dis [Pages] => 2024;3:86–91 [Recommend] => 0 [Keywords] => Remarkable alpha-fetoprotein elevation, portal vein thrombosis, liver cirrhosis, liver pseudo-infarction, case report [DetailTitle] => [DetailUrl] => [Id] => 100541 [ris] => https://www.explorationpub.com/uploads/Article/A100541/9b5ca1816d3382b3ebfc67a85bcee52c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100541/52c96e24e500e576739d53baa778205c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Elghannam MT, Hassanien MH, Ameen YA, Elattar GM, ELRay AA, ELTalkawy MD. Remarkable alpha-fetoprotein elevation and pseudo-infarction of cirrhotic liver: case report. Explor Dig Dis. 2024;3:86–91. https://doi.org/10.37349/edd.2024.00041 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-09 03:02:37 [Bib_Time] => 2024-03-27 07:27:39 [KeysWordContens] => Remarkable alpha-fetoprotein elevation and pseudo-infarction of cirrhotic liver: case report, Remarkable alpha-fetoprotein elevation, portal vein thrombosis, liver cirrhosis, liver pseudo-infarction, case report, This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction. ,Maged Tharwat Elghannam ... Mohammed Darwish ELTalkawy [PublishedText] => Published [IsEdit] => 0 [AccountId] => 78 [Zh] => 1 ) [41] => Array ( [ArticleId] => 1219 [Create_Time] => 2024-04-10 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240410071819.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100542/100542.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100542/100542.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100542/100542_cover.png [JournalsId] => 6 [Title] => Second- and third-line treatment agents in autoimmune hepatitis (AIH): Where do we stand? [Abstract] => Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are [AbstractComplete] =>Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.
[Names] => Pinelopi Arvaniti ... Maria-Carlota Londoño [Doi] => 10.37349/edd.2024.00042 [Published] => April 10, 2024 [Viewed] => 96 [Downloaded] => 4 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/edd.2024.00042 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 0 [TitleAbbr] => Explor Dig Dis [Pages] => 2024;3:92–106 [Recommend] => 0 [Keywords] => Autoimmune hepatitis, complete biochemical response, second line treatment, third line treatment [DetailTitle] => [DetailUrl] => [Id] => 100542 [ris] => https://www.explorationpub.com/uploads/Article/A100542/8f0d1b3093df41eb815e7260c47f4c41.ris [bib] => https://www.explorationpub.com/uploads/Article/A100542/1335922202ae108502eeaa5619757a8c.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Arvaniti P, Olivas I, Rodriguez-Tajes S, Dalekos GN, Londoño MC. Second- and third-line treatment agents in autoimmune hepatitis (AIH): Where do we stand? Explor Dig Dis. 2024;3:92–106. https://doi.org/10.37349/edd.2024.00042 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-09 03:09:02 [Bib_Time] => 2024-04-09 03:09:02 [KeysWordContens] => Second- and third-line treatment agents in autoimmune hepatitis (AIH): Where do we stand?, Autoimmune hepatitis, complete biochemical response, second line treatment, third line treatment, Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies. ,Pinelopi Arvaniti ... Maria-Carlota Londoño [PublishedText] => Published [IsEdit] => 0 [AccountId] => 78 [Zh] => 0 ) [42] => Array ( [ArticleId] => 1239 [Create_Time] => 2024-04-16 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240416055140.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100543/100543.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100543/100543.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100543/100543_cover.png [JournalsId] => 6 [Title] => Helicobacter pylori and gastric cancer: a critical approach to who really needs eradication [Abstract] => It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and trea [AbstractComplete] =>It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and treat all individuals detected positive for H. pylori infection are currently proposed. However, the bacterium is commensal and harmless for the vast majority of the infected population. Moreover, eradication may have detrimental consequences in several groups of patients. In the present review, the current epidemiological data and recommendations for eradication in connection with the possible beneficial effects of the colonization with H. pylori in diseases such as asthma and allergies or chronic gastro-intestinal disorders such as inflammatory bowel disease and Barrett’ esophagus are presented the problems with increasing antibiotic resistance were also examined. Specific groups of patients where eradication of H. pylori may be necessary and endoscopic surveillance is advised were identified. Finally, based on the paradox of high H. pylori prevalence and low gastric risk as reported for areas of Africa, Asia, South America, and Greece, alternatives that may replace the widespread eradication of H. pylori with equal if not better results and more prudent use of the available financial resources are proposed. Mediterranean diets and alcohol and smoking reduction are among the well documented alternatives.
[Names] => Elias Kouroumalis ... Argyro Voumvouraki [Doi] => 10.37349/edd.2024.00043 [Published] => April 16, 2024 [Viewed] => 86 [Downloaded] => 2 [Subject] => Review [Year] => 2024 [CiteUrl] => https://doi.org/10.37349/edd.2024.00043 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 213 [TitleAbbr] => Explor Dig Dis. [Pages] => 2024;3:107–142 [Recommend] => 0 [Keywords] => Helicobacter pylori, eradication, gastric cancer, Mediterranean diet [DetailTitle] => Helicobacter Pylori and Infection: Genomics, Diagnosis, Pathogenesis, Antibiotic Resistance, Microbiota, Cancer, Prevention and Therapeutics [DetailUrl] => https://www.explorationpub.com/Journals/edd/Special_Issues/213 [Id] => 100543 [ris] => https://www.explorationpub.com/uploads/Article/A100543/929cbc6e2c5fc2e1ef9111801113caaa.ris [bib] => https://www.explorationpub.com/uploads/Article/A100543/54f9fce7b6599b118b823b9f0d087a07.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kouroumalis E, Tsomidis I, Voumvouraki A. Helicobacter pylori and gastric cancer: a critical approach to who really needs eradication. Explor Dig Dis. 2024;3:107–42. https://doi.org/10.37349/edd.2024.00043 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-16 02:12:21 [Bib_Time] => 2024-04-16 02:12:21 [KeysWordContens] => Helicobacter pylori and gastric cancer: a critical approach to who really needs eradication, Helicobacter pylori, eradication, gastric cancer, Mediterranean diet, It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and treat all individuals detected positive for H. pylori infection are currently proposed. However, the bacterium is commensal and harmless for the vast majority of the infected population. Moreover, eradication may have detrimental consequences in several groups of patients. In the present review, the current epidemiological data and recommendations for eradication in connection with the possible beneficial effects of the colonization with H. pylori in diseases such as asthma and allergies or chronic gastro-intestinal disorders such as inflammatory bowel disease and Barrett’ esophagus are presented the problems with increasing antibiotic resistance were also examined. Specific groups of patients where eradication of H. pylori may be necessary and endoscopic surveillance is advised were identified. Finally, based on the paradox of high H. pylori prevalence and low gastric risk as reported for areas of Africa, Asia, South America, and Greece, alternatives that may replace the widespread eradication of H. pylori with equal if not better results and more prudent use of the available financial resources are proposed. Mediterranean diets and alcohol and smoking reduction are among the well documented alternatives. ,Elias Kouroumalis ... Argyro Voumvouraki [PublishedText] => Published [IsEdit] => 0 [AccountId] => 69 [Zh] => 0 ) [43] => Array ( [ArticleId] => 1261 [Create_Time] => 2024-04-24 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240425080212.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100544/100544.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100544/100544.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100544/100544_cover.png [JournalsId] => 6 [Title] => Optimization of protocols for blood-derived extracellular vesicles for studies in liver diseases [Abstract] => Aim: Extracellular vesicles (EVs) have gained significant attention for their diagnostic and therapeutic potential in various diseases, including liver disorders. This study focuses on optimizing [AbstractComplete] =>Extracellular vesicles (EVs) have gained significant attention for their diagnostic and therapeutic potential in various diseases, including liver disorders. This study focuses on optimizing the isolation and characterization of small EVs from plasma and serum samples in patients with liver diseases, aiming to advance our understanding and potential clinical applications of EVs.
Blood samples were collected from patients with end-stage liver disease (ESLD) enlisted in the TransplantLines Cohort and Biobank Study, and healthy donors. We employed differential ultracentrifugation (DUC) to evaluate three distinct protocols: a 3-step DUC, a washing step omitted [samples without washing (WW)], and a contaminant-depleted plasma (CDP) protocol. RNA isolation methodologies were compared, involving the use of TRI-reagent or the commercial AllPrep DNA/RNA kit. Further insights into EV composition were obtained through proteomic analyses, comparing samples subjected to traditional cell lysis (L) with those processed without lysis (NL).
We successfully isolated EVs from both plasma and serum samples as confirmed by the presence of specific EV markers, including CD9, CD63, CD81, and tumor susceptibility gene 101 (TSG-101). While some contaminants remained, such as albumin and lipoproteins, the protocol selected to continue EVs analysis was the 3-step protocol. Transmission electron microscopy (TEM) and nanotracking analysis (NTA) further confirmed EVs presence. RNA extraction was achieved using TRI-reagent, but not with the commercial kit highlighting the importance of selecting an appropriate method for RNA isolation. Finally, proteomics analysis showed that lysed samples were significantly more enriched in proteins compared to non-lysed samples, although protein variability was still present in both groups.
Optimizing EV isolation techniques is essential for harnessing their potential in liver disease diagnosis and therapy. Further refinement of purification methods, a deep characterization of our cohort and understanding the variability and cargo within EVs will be crucial for future biomarker discovery and therapeutic applications in liver-related diseases.