Previous
Aim:
This study aimed to identify and analyze the top 100 most cited digital health and mobile health (m-health) publications. It could aid researchers in the identification of promising new research avenues, additionally supporting the establishment of international scientific collaboration between interdisciplinary research groups with demonstrated achievements in the area of interest.
Methods:
On 30th August, 2023, the Web of Science Core Collection (WOSCC) electronic database was queried to identify the top 100 most cited digital health papers with a comprehensive search string. From the initial search, 106 papers were identified. After screening for relevance, six papers were excluded, resulting in the final list of the top 100 papers. The basic bibliographic data was directly extracted from WOSCC using its “Analyze” and “Create Citation Report” functions. The complete records of the top 100 papers were downloaded and imported into a bibliometric software called VOSviewer (version 1.6.19) to generate an author keyword map and author collaboration map.
Results:
The top 100 papers on digital health received a total of 49,653 citations. Over half of them (n = 55) were published during 2013–2017. Among these 100 papers, 59 were original articles, 36 were reviews, 4 were editorial materials, and 1 was a proceeding paper. All papers were written in English. The University of London and the University of California system were the most represented affiliations. The USA and the UK were the most represented countries. The Journal of Medical Internet Research was the most represented journal. Several diseases and health conditions were identified as a focus of these works, including anxiety, depression, diabetes mellitus, cardiovascular diseases, and coronavirus disease 2019 (COVID-19).
Conclusions:
The findings underscore key areas of focus in the field and prominent contributors, providing a roadmap for future research in digital and m-health.
Aim:
This study aimed to identify and analyze the top 100 most cited digital health and mobile health (m-health) publications. It could aid researchers in the identification of promising new research avenues, additionally supporting the establishment of international scientific collaboration between interdisciplinary research groups with demonstrated achievements in the area of interest.
Methods:
On 30th August, 2023, the Web of Science Core Collection (WOSCC) electronic database was queried to identify the top 100 most cited digital health papers with a comprehensive search string. From the initial search, 106 papers were identified. After screening for relevance, six papers were excluded, resulting in the final list of the top 100 papers. The basic bibliographic data was directly extracted from WOSCC using its “Analyze” and “Create Citation Report” functions. The complete records of the top 100 papers were downloaded and imported into a bibliometric software called VOSviewer (version 1.6.19) to generate an author keyword map and author collaboration map.
Results:
The top 100 papers on digital health received a total of 49,653 citations. Over half of them (n = 55) were published during 2013–2017. Among these 100 papers, 59 were original articles, 36 were reviews, 4 were editorial materials, and 1 was a proceeding paper. All papers were written in English. The University of London and the University of California system were the most represented affiliations. The USA and the UK were the most represented countries. The Journal of Medical Internet Research was the most represented journal. Several diseases and health conditions were identified as a focus of these works, including anxiety, depression, diabetes mellitus, cardiovascular diseases, and coronavirus disease 2019 (COVID-19).
Conclusions:
The findings underscore key areas of focus in the field and prominent contributors, providing a roadmap for future research in digital and m-health.
DOI: https://doi.org/10.37349/edht.2024.00013
Aim:
Currently, malignant diseases represent a health issue worldwide. Among these, lung cancer is of growing importance, due to its high incidence and mortality. Chemotherapy, one of the most frequently used treatments, has shown its ability to induce accelerated immunosenescence in classic and as well non-classic lymphocyte compartments, being less described in the latter. The immune restoration strategies have demonstrated their ability to reverse immunosenescence and exhaustion markers in conventional lymphocyte subpopulations after chemotherapy. However, the possible immunorestorative effect on non-classical lymphocytes has not been widely reported. The aim of this study was to evaluate the effect of chemotherapy and the administration of a thymic polypepti
Methods:
Eighteen patients with advanced lung cancer, were evaluated at baseline before and after platinum-based chemotherapy (4–6 cycles). All patients could complete treatment with a thymic polypepti
Results:
Natural killer (NK), natural killer T cells (NKT), and double-positive T lymphocyte (DPT) proportions reached normal values in patients diagnosed with advanced lung cancer before receiving cytotoxic treatment. Chemotherapy did not induce modifications in the total percent of NK, NKT, and DPT populations in these patients. However, the administration of BT decreased DPTs and NK cells expressing the cluster of differentiation (CD)57 molecule, which is considered a marker of immunosenescence.
Conclusions:
These results suggest a lower influence of platinum-based chemotherapy on non-classical lymphocytes and the potential to generate a reconstitution of lymphocyte subpopulations in patients with advanced lung cancer by using the thymic factor BT, which reveals a new possibility for improving the response to cancer immunotherapies [Cuban Public Registry of Clinical Trial (RPCEC, https://rpcec.sld.cu/en/trials/RPCEC00000358-En) identifier: RPCEC00000358].
Aim:
Currently, malignant diseases represent a health issue worldwide. Among these, lung cancer is of growing importance, due to its high incidence and mortality. Chemotherapy, one of the most frequently used treatments, has shown its ability to induce accelerated immunosenescence in classic and as well non-classic lymphocyte compartments, being less described in the latter. The immune restoration strategies have demonstrated their ability to reverse immunosenescence and exhaustion markers in conventional lymphocyte subpopulations after chemotherapy. However, the possible immunorestorative effect on non-classical lymphocytes has not been widely reported. The aim of this study was to evaluate the effect of chemotherapy and the administration of a thymic polypepti
Methods:
Eighteen patients with advanced lung cancer, were evaluated at baseline before and after platinum-based chemotherapy (4–6 cycles). All patients could complete treatment with a thymic polypepti
Results:
Natural killer (NK), natural killer T cells (NKT), and double-positive T lymphocyte (DPT) proportions reached normal values in patients diagnosed with advanced lung cancer before receiving cytotoxic treatment. Chemotherapy did not induce modifications in the total percent of NK, NKT, and DPT populations in these patients. However, the administration of BT decreased DPTs and NK cells expressing the cluster of differentiation (CD)57 molecule, which is considered a marker of immunosenescence.
Conclusions:
These results suggest a lower influence of platinum-based chemotherapy on non-classical lymphocytes and the potential to generate a reconstitution of lymphocyte subpopulations in patients with advanced lung cancer by using the thymic factor BT, which reveals a new possibility for improving the response to cancer immunotherapies [Cuban Public Registry of Clinical Trial (RPCEC, https://rpcec.sld.cu/en/trials/RPCEC00000358-En) identifier: RPCEC00000358].
DOI: https://doi.org/10.37349/ei.2024.00150
Aim:
B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the in vitro and in vivo properties associated with melanoma aggressive features has been investigated.
Methods:
Endogenous Bcl2L10 protein expression was detected by western blotting analysis in a panel of patient-derived and commercially available human melanoma cells. In vitro assays to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been performed by using human melanoma cells stably overexpressing Bcl2L10 or transiently transfected for loss/gain function of Bcl2L10, grown under two- or three-dimensional (3D) conditions Xenograft melanoma model was employed to evaluate in vivo tumor growth and angiogenesis.
Results:
Results demonstrated that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, while in vitro cell proliferation, in vivo tumor growth, as well as colony formation properties were not affected. Dissecting different signaling pathways, it was found that Bcl2L10 positively affects the phosphorylation of extracellular-signal-regulated kinase (ERK) and the expression of markers of cell invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the intracellular calcium level. Finally, reduced invasion capability in 3D spheroid invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed after treatment with inhibitors of MMPs and uPAR.
Conclusions:
Overall, data reported in this paper provi
Aim:
B-cell lymphoma-2 (Bcl-2)-like protein-10 (Bcl2L10) is the less studied member of Bcl-2 family proteins, with the controversial role in different cancer histotypes. Very recently, Bcl2L10 expression in melanoma tumor specimens and its role in melanoma response to therapy have been demonstrated. Here, the involvement of Bcl2L10 on the in vitro and in vivo properties associated with melanoma aggressive features has been investigated.
Methods:
Endogenous Bcl2L10 protein expression was detected by western blotting analysis in a panel of patient-derived and commercially available human melanoma cells. In vitro assays to evaluate clonogenicity, cell proliferation, cell migration, cell invasion, and in vitro capillary-like structure formation [vasculogenic mimicry (VM)] have been performed by using human melanoma cells stably overexpressing Bcl2L10 or transiently transfected for loss/gain function of Bcl2L10, grown under two- or three-dimensional (3D) conditions Xenograft melanoma model was employed to evaluate in vivo tumor growth and angiogenesis.
Results:
Results demonstrated that Bcl2L10 acts as an inducer of in vitro cell migration, invasion, and VM, while in vitro cell proliferation, in vivo tumor growth, as well as colony formation properties were not affected. Dissecting different signaling pathways, it was found that Bcl2L10 positively affects the phosphorylation of extracellular-signal-regulated kinase (ERK) and the expression of markers of cell invasion, such as urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinases (MMPs). Of note, Bcl2L10-dependent in vitro migration, invasion, and VM are linked to uPAR. Bcl2L10 also negatively regulates the intracellular calcium level. Finally, reduced invasion capability in 3D spheroid invasion assay of melanoma cells transiently overexpressing Bcl2L10 was observed after treatment with inhibitors of MMPs and uPAR.
Conclusions:
Overall, data reported in this paper provi
DOI: https://doi.org/10.37349/etat.2022.00068
This article belongs to the special issue The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy
Aim:
The present study aims to generate chimeric mouse single-chain variable fragment (scFv) and immunoglobulin G1 (IgG1) crystallizable fragment (Fc) antibody against disialogangliosi
Methods:
Vector for scFv-IgG
Results:
Using plasmid fusion-human IgG1-Fc2 tag vector (pFUSE-hIgG1-Fc2), a plasmid vector encoding chimeric mouse scFv and hIgG1
Conclusions:
The results indicate that chimeric scFv-hIgG
Aim:
The present study aims to generate chimeric mouse single-chain variable fragment (scFv) and immunoglobulin G1 (IgG1) crystallizable fragment (Fc) antibody against disialogangliosi
Methods:
Vector for scFv-IgG
Results:
Using plasmid fusion-human IgG1-Fc2 tag vector (pFUSE-hIgG1-Fc2), a plasmid vector encoding chimeric mouse scFv and hIgG1
Conclusions:
The results indicate that chimeric scFv-hIgG
DOI: https://doi.org/10.37349/etat.2023.00188
This article belongs to the special issue Novel Strategies and Targets for Immunotherapy of Cancer
Aim:
The aim of this research was to generate new pepti
Methods:
Hybrid peptides and precursors were synthesized by solid-phase pepti
Results:
All hybrid peptides were obtained with high purity and the experimental mass corresponds with the theoretical mass. Some hybrid peptides exhibited significant, fast, and selective cytotoxic activity against the cancerous cells evaluated, specifically those containing sequences of anticancer peptides and cell-penetrating peptides. The cytotoxic effect exerted by the monomeric and dimeric hybrid peptides depended on the concentration of the peptide, which allowed the determination of the IC50 values and the selectivity index (SI).
Conclusions:
We obtained hybrid peptides with the core sequence RWQWRWQWR that are active against He
Aim:
The aim of this research was to generate new pepti
Methods:
Hybrid peptides and precursors were synthesized by solid-phase pepti
Results:
All hybrid peptides were obtained with high purity and the experimental mass corresponds with the theoretical mass. Some hybrid peptides exhibited significant, fast, and selective cytotoxic activity against the cancerous cells evaluated, specifically those containing sequences of anticancer peptides and cell-penetrating peptides. The cytotoxic effect exerted by the monomeric and dimeric hybrid peptides depended on the concentration of the peptide, which allowed the determination of the IC50 values and the selectivity index (SI).
Conclusions:
We obtained hybrid peptides with the core sequence RWQWRWQWR that are active against He
DOI: https://doi.org/10.37349/eds.2024.00064
This article belongs to the special issue Bioactive Peptides: Pioneering Innovations in Latin American Research
Aim:
Inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitous calcium (Ca2+) channel involved in the regulation of cellular fate and motility. Its modulation by anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) plays an important role in cancer progression. Disrupting this interaction could overcome apoptosis avoidance, one of the hallmarks of cancer, and is, thus, of great interest. Earlier reports have shown the involvement of both the Bcl-2 homology 4 (BH4) and the transmembrane domains (TMDs) of Bcl-2 in regulating IP3R activity, while the Bcl-2 hydrophobic cleft was associated primarily with its anti-apoptotic and IP3R-independent action at the mitochondria (Oncotarget. 2016;7:55704–20. doi: 10.18632/oncotarget.11005). The aim of this study was to investigate how targeting the BH3 hydrophobic cleft of Bcl-2 affects IP3R:Bcl-2 interaction.
Methods:
Organelle membrane-derived (OMD) patch-clamp and circular dichroism (CD) thermal melting experiments were used to elucidate the effects of the ABT-199 (venetoclax) on the IP3R:Bcl-2 interaction. Molecular dynamics (MD) simulations of free and ABT-199 bound Bcl-2 were used to propose a molecular model of such interaction.
Results:
It was shown that occlusion of Bcl-2’s hydrophobic cleft by the drug ABT-199 finely modulates IP3R gating in the low open probability (Po) regime, characteristic of the basal IP3R activity in non-excited cells. Complementary MD simulations allowed to propose a model of this modulation, involving an allosteric interaction with the BH4 domain on the opposite si
Conclusions:
Bcl-2 is an important regulator of IP3R activity and, thus of Ca2+ release from internal stores and associated processes, including cellular proliferation and death. The presence of multiple regulatory domains in both proteins suggests a complex interaction. Thus, it was found that the occlusion of the hydrophobic cleft of Bcl-2 by ABT-199 disrupts IP3R activity, leading to Bcl-2 rebinding with smaller affinity and lesser inhibitory effect. MDs simulations of free and ABT-199 bound Bcl-2 propose a molecular model of such disruption, involving an allosteric interaction with the BH4 domain on the opposite si
Aim:
Inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitous calcium (Ca2+) channel involved in the regulation of cellular fate and motility. Its modulation by anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) plays an important role in cancer progression. Disrupting this interaction could overcome apoptosis avoidance, one of the hallmarks of cancer, and is, thus, of great interest. Earlier reports have shown the involvement of both the Bcl-2 homology 4 (BH4) and the transmembrane domains (TMDs) of Bcl-2 in regulating IP3R activity, while the Bcl-2 hydrophobic cleft was associated primarily with its anti-apoptotic and IP3R-independent action at the mitochondria (Oncotarget. 2016;7:55704–20. doi: 10.18632/oncotarget.11005). The aim of this study was to investigate how targeting the BH3 hydrophobic cleft of Bcl-2 affects IP3R:Bcl-2 interaction.
Methods:
Organelle membrane-derived (OMD) patch-clamp and circular dichroism (CD) thermal melting experiments were used to elucidate the effects of the ABT-199 (venetoclax) on the IP3R:Bcl-2 interaction. Molecular dynamics (MD) simulations of free and ABT-199 bound Bcl-2 were used to propose a molecular model of such interaction.
Results:
It was shown that occlusion of Bcl-2’s hydrophobic cleft by the drug ABT-199 finely modulates IP3R gating in the low open probability (Po) regime, characteristic of the basal IP3R activity in non-excited cells. Complementary MD simulations allowed to propose a model of this modulation, involving an allosteric interaction with the BH4 domain on the opposite si
Conclusions:
Bcl-2 is an important regulator of IP3R activity and, thus of Ca2+ release from internal stores and associated processes, including cellular proliferation and death. The presence of multiple regulatory domains in both proteins suggests a complex interaction. Thus, it was found that the occlusion of the hydrophobic cleft of Bcl-2 by ABT-199 disrupts IP3R activity, leading to Bcl-2 rebinding with smaller affinity and lesser inhibitory effect. MDs simulations of free and ABT-199 bound Bcl-2 propose a molecular model of such disruption, involving an allosteric interaction with the BH4 domain on the opposite si
DOI: https://doi.org/10.37349/etat.2022.00088
This article belongs to the special issue The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy
Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials. From clinicaltrials.gov online database all ongoing trials for BTCs (any stage) was examinated in July 2021, and data regarding study design, disease characteristics and type of treatments were registered. Oncogenic-driven therapy (targeted therapy) was investigated in 67 trials. According to research, 15 ongoing trials (22.4%) are investigating fibroblast growth factor (FGF) receptor (FGFR)-inhibitors in BTCs. Three (18.7%) are open-label randomized multicenter phase 3 trials, 8 (50%) are single-arm phase two trials, and 4 (25%) are phase one studies. Twelve (17.9%) clinical trials dealt with isocitrate dehydrogenase (IDH) 1/2 targeting therapy either in combination with cisplatin (Cis) and gemcitabine (Gem) as first-line treatment for BTCs or in monotherapy in patients with IDH1 mutant advanced malignancies, including cholangiocarcinoma (CCA). Nine (13.4%) clinical trials tested human epidermal growth factor receptor (HER) 2 targeting therapy. Four (44.4%) studies are phase I trials, two (22.2%) are phase I/II trials, and three (33.3%) phase II trials. Rare molecular alterations in BTCs, such as anaplastic lymphoma kinase (ALK), c-ros oncogene1 receptor tyrosine kinase (ROS1), and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF), are also under investigation in a few trials. Forty-four clinical trials (17.2%) are investigating not oncogenic-driven multitarget therapy like multireceptor tyrosin kinase inhibitors and antiangiogenetic agents. In conclusion, this review shows that BTCs management is experiencing important innovations, especially in biomarker-based patient selection and in the new emerging therapeutic approach. Many ongoing trials could answer questions regarding the role of molecular inhibitors leading to new therapeutic frontiers for molecular subcategories of BTCs.
Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials. From clinicaltrials.gov online database all ongoing trials for BTCs (any stage) was examinated in July 2021, and data regarding study design, disease characteristics and type of treatments were registered. Oncogenic-driven therapy (targeted therapy) was investigated in 67 trials. According to research, 15 ongoing trials (22.4%) are investigating fibroblast growth factor (FGF) receptor (FGFR)-inhibitors in BTCs. Three (18.7%) are open-label randomized multicenter phase 3 trials, 8 (50%) are single-arm phase two trials, and 4 (25%) are phase one studies. Twelve (17.9%) clinical trials dealt with isocitrate dehydrogenase (IDH) 1/2 targeting therapy either in combination with cisplatin (Cis) and gemcitabine (Gem) as first-line treatment for BTCs or in monotherapy in patients with IDH1 mutant advanced malignancies, including cholangiocarcinoma (CCA). Nine (13.4%) clinical trials tested human epidermal growth factor receptor (HER) 2 targeting therapy. Four (44.4%) studies are phase I trials, two (22.2%) are phase I/II trials, and three (33.3%) phase II trials. Rare molecular alterations in BTCs, such as anaplastic lymphoma kinase (ALK), c-ros oncogene1 receptor tyrosine kinase (ROS1), and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF), are also under investigation in a few trials. Forty-four clinical trials (17.2%) are investigating not oncogenic-driven multitarget therapy like multireceptor tyrosin kinase inhibitors and antiangiogenetic agents. In conclusion, this review shows that BTCs management is experiencing important innovations, especially in biomarker-based patient selection and in the new emerging therapeutic approach. Many ongoing trials could answer questions regarding the role of molecular inhibitors leading to new therapeutic frontiers for molecular subcategories of BTCs.
DOI: https://doi.org/10.37349/etat.2021.00056
This article belongs to the special issue Precision Medicine for Cholangiocarcinoma
In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in
In patients with autoimmune coagulation factor deficiency (AiCFD), the production of autoantibodies that inhibit coagulation factors in the blood reduces the activity of those relevant coagulation factors, resulting in severe bleeding symptoms. Recently, reports of patients with AiCFD have noted the concomitant detection of lupus anticoagulant (LA), a risk factor for thrombosis. LA-positive patients may show bleeding symptoms due to decreased activity of coagulation factor II (FII) caused by autoantibodies against FII, in addition to thrombotic symptoms, a condition termed LA-hypoprothrombinemia syndrome (LAHPS). Anti-FII antibodies in LAHPS cases are frequently cleared antibodies that can be detected using immunological techniques, such as enzyme-linked immunosorbent assay (ELISA). Recently, several cases of coagulation FV inhibitors, known as autoimmune FV deficiency, have been reported. Some of these cases may be complicated by LA, which can cause thrombosis. False-positive results for anticoagulant inhibitors are known to occur in
DOI: https://doi.org/10.37349/ei.2023.00103
This article belongs to the special issue Autoantibodies Associated to Thrombosis and Hemostasis
Aim:
This study discloses the synthesis and the antimicrobial and anticancer activities of four molecules of structural basis saccharin-thiadiazolyl (4), saccharin-pyridyl (6, 8), and tetrazole-thiadiazolyl (11).
Methods:
Antimicrobial properties of the molecules were evaluated by the well-diffusion method, against Gram-positive bacteria [Staphylococcus aureus American Type Culture Collection (ATCC) 25923, Staphylococcus epidermidis ATCC 12228, Mycobacterium smegmatis ATCC 607], Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853) and yeast (Saccharomyces cerevisiae ATCC 2601 and Candida albicans ATCC 10231) strains. The anticancer activity of the compounds was assessed through i) proliferation assays for HCT116, MCF-7, and A375 human cell lines [cells were treated with serial dilutions of compounds and the effect on cell propagation was evaluated by sulforhodamine B (SRB) assay]; ii) antiproliferative and cytotoxic assays for glioma-type cell lines A172 (glioblastoma), U87 (brain-likely glioblastoma), and H4 (neuroglioma; cells were treated with diverse concentrations and the cell viability was assessed using a modified Alamar blue® assay).
Results:
Compound 11 exhibited significant inhibitory activity against S. aureus and S. epidermidis, with the further molecules demonstrating some inhibitory potential against all the tested Gram-positive, Gram-negative, and yeast strains. Similarly, derivative 11 showed an interesting antiproliferative activity against human colon adenocarcinoma (HCT116), human breast adenocarcinoma (MCF-7), and melanoma (A375) cells, with 50% growth inhibition (GI50) values varying from 3.55 µmol/L to 11.5 µmol/L, in the same order of magnitu
Conclusions:
This investigation reveals the potential of distinct azole-based conjugates, in particular the tetrazole-thiadiazolyl (11) derivative, as scaffolds worth further investigations, in the frame of antimicrobial and antineoplastic chemotherapy.
Aim:
This study discloses the synthesis and the antimicrobial and anticancer activities of four molecules of structural basis saccharin-thiadiazolyl (4), saccharin-pyridyl (6, 8), and tetrazole-thiadiazolyl (11).
Methods:
Antimicrobial properties of the molecules were evaluated by the well-diffusion method, against Gram-positive bacteria [Staphylococcus aureus American Type Culture Collection (ATCC) 25923, Staphylococcus epidermidis ATCC 12228, Mycobacterium smegmatis ATCC 607], Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853) and yeast (Saccharomyces cerevisiae ATCC 2601 and Candida albicans ATCC 10231) strains. The anticancer activity of the compounds was assessed through i) proliferation assays for HCT116, MCF-7, and A375 human cell lines [cells were treated with serial dilutions of compounds and the effect on cell propagation was evaluated by sulforhodamine B (SRB) assay]; ii) antiproliferative and cytotoxic assays for glioma-type cell lines A172 (glioblastoma), U87 (brain-likely glioblastoma), and H4 (neuroglioma; cells were treated with diverse concentrations and the cell viability was assessed using a modified Alamar blue® assay).
Results:
Compound 11 exhibited significant inhibitory activity against S. aureus and S. epidermidis, with the further molecules demonstrating some inhibitory potential against all the tested Gram-positive, Gram-negative, and yeast strains. Similarly, derivative 11 showed an interesting antiproliferative activity against human colon adenocarcinoma (HCT116), human breast adenocarcinoma (MCF-7), and melanoma (A375) cells, with 50% growth inhibition (GI50) values varying from 3.55 µmol/L to 11.5 µmol/L, in the same order of magnitu
Conclusions:
This investigation reveals the potential of distinct azole-based conjugates, in particular the tetrazole-thiadiazolyl (11) derivative, as scaffolds worth further investigations, in the frame of antimicrobial and antineoplastic chemotherapy.
DOI: https://doi.org/10.37349/eds.2023.00028
Neuregulins (NRGs) and their cognate ErbB receptors (ErbB2–ErbB4) constitute a vast group of proteins encoded by six different genes (NRG1–6) and many isoforms with critical roles in the development and functioning of the nervous system. NRGs are known to regulate important processes in the nervous system like neural development, neuronal differentiation, neurite outgrowth, and specification. These factors are involved in the regulation of neurotransmission pathways and the modulation of several forms of synaptic plasticity. Due to NRGs’ role in synaptic plasticity, defects in their normal functioning are translated into altered signaling networks, which have been linked to susceptibility to developing psychiatric disorders like schizophrenia (SZ), autism, depression, and bipolar disorders. Additionally, deviation of the NRG normal functioning is involved in neurological diseases like Alzheimer’s and Parkinson’s disease. Contrastingly, NRG/ErbB signaling is also involved in the recovery after traumatic brain injuries (e.g., ischemic stroke). The NRG/ErbB signaling complex is highly unusual because the ligands (mainly NRG1–NRG3, with their multiple isoforms) and receptors (ErbB2–ErbB4) can orchestrate vast signaling complexes, with a wi
Neuregulins (NRGs) and their cognate ErbB receptors (ErbB2–ErbB4) constitute a vast group of proteins encoded by six different genes (NRG1–6) and many isoforms with critical roles in the development and functioning of the nervous system. NRGs are known to regulate important processes in the nervous system like neural development, neuronal differentiation, neurite outgrowth, and specification. These factors are involved in the regulation of neurotransmission pathways and the modulation of several forms of synaptic plasticity. Due to NRGs’ role in synaptic plasticity, defects in their normal functioning are translated into altered signaling networks, which have been linked to susceptibility to developing psychiatric disorders like schizophrenia (SZ), autism, depression, and bipolar disorders. Additionally, deviation of the NRG normal functioning is involved in neurological diseases like Alzheimer’s and Parkinson’s disease. Contrastingly, NRG/ErbB signaling is also involved in the recovery after traumatic brain injuries (e.g., ischemic stroke). The NRG/ErbB signaling complex is highly unusual because the ligands (mainly NRG1–NRG3, with their multiple isoforms) and receptors (ErbB2–ErbB4) can orchestrate vast signaling complexes, with a wi
DOI: https://doi.org/10.37349/en.2022.00003
Carpal tunnel syndrome (CTS) is the most common type of entrapment neuropathy and affects approximately 1% to 5% of the general population, mostly patients older than 50 years. CTS is present in various conditions and diseases and could also be an early sign of systemic transthyretin amyloidosis (ATTR), associated with amyloid cardiomyopathy and subsequent heart failure. With advances in the treatment of cardiac amyloidosis, patient prognosis could be significantly improved with an early diagnosis. Amyloidosis represents a group of disorders characterized by the extracellular deposition of destabilized protein fragments, aggregating as amyloid fibrils, thereby leading to organ dysfunction. Among these, ATTR is a significant subgroup. This study protocol aims to explore the potential association between CTS and systemic and cardiac ATTR. The study design involves a case-control approach, with assessments including physical examination, laboratory tests, electromyography, electrocardiogram, wrist ultrasound, and scintigraphy with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD). Histopathological analysis and genetic testing will be performed when appropriate. Statistical analysis will be conducted to evaluate the relationship between CTS and ATTR. The study seeks to contribute to a better understanding of the diagnostic and therapeutic implications of identifying ATTR in patients with idiopathic CTS (ClinicalTrials.gov identifier: NCT05409833).
Carpal tunnel syndrome (CTS) is the most common type of entrapment neuropathy and affects approximately 1% to 5% of the general population, mostly patients older than 50 years. CTS is present in various conditions and diseases and could also be an early sign of systemic transthyretin amyloidosis (ATTR), associated with amyloid cardiomyopathy and subsequent heart failure. With advances in the treatment of cardiac amyloidosis, patient prognosis could be significantly improved with an early diagnosis. Amyloidosis represents a group of disorders characterized by the extracellular deposition of destabilized protein fragments, aggregating as amyloid fibrils, thereby leading to organ dysfunction. Among these, ATTR is a significant subgroup. This study protocol aims to explore the potential association between CTS and systemic and cardiac ATTR. The study design involves a case-control approach, with assessments including physical examination, laboratory tests, electromyography, electrocardiogram, wrist ultrasound, and scintigraphy with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD). Histopathological analysis and genetic testing will be performed when appropriate. Statistical analysis will be conducted to evaluate the relationship between CTS and ATTR. The study seeks to contribute to a better understanding of the diagnostic and therapeutic implications of identifying ATTR in patients with idiopathic CTS (ClinicalTrials.gov identifier: NCT05409833).
DOI: https://doi.org/10.37349/ec.2024.00035
Aim:
Excitotoxicity results from unusually increased activation of excitatory amino acid receptors leading to neuronal death. Since glutamate is the main excitatory neurotransmitter in the central nervous system, it is also the most common excitotoxicity trigger. This uncontrolled neuronal response participates in various neurodegenerative diseases, such as ischemia, hypoglycemia, Huntington’s, Parkinson’s and Alzheimer’s disease. Thus, the investigation in the field expanded a lot in the past decade, leading to in vitro modelling adaptations. However, much performed work on glutamate-induced excitotoxicity is methodologically inconsistent in the literature. The field lacks reproducibility, which is one of the main fundaments of empirical science. In this regard, the literature was summarized and the main methodological features were critically evaluated, aiming to gui
Methods:
Published data since 1985 from PUBMED were collected and analyzed to observe which in vitro experimental conditions of excitotoxicity were reproducible. The suggested methods were based on the characteristics of excitotoxicity, such as abnormal intracellular calcium mediated signaling, mitochondria impairment, reactive oxygen species accumulation and cell death. Various conditions and comparative controls were used to design the standard investigation of excitotoxicity, such as culture medium content (presence of glutamate and aspartate), time interval of induction and the concentration of the inductor, based on the most reproducible published ones.
Results:
Our results and critical analysis point to some experimental conditions to consider, such as primary cultured neurons are more sensitive to glutamate and the response obtained is more robust than in other models; excitotoxicity mediated effects are better observed one hour following the stimulus; the culture medium should contain low levels of glutamate or aspartate or glycine. Online available phosphoproteomic data on excitotoxicity using the primary cortical neurons in vitro model supported the same conditions proposed by us.
Conclusions:
This manuscript will facilitate the design of any research for excitotoxic or neuroprotective compounds in physiological and pathophysiological conditions by standardizing and improving experimental conditions.
Aim:
Excitotoxicity results from unusually increased activation of excitatory amino acid receptors leading to neuronal death. Since glutamate is the main excitatory neurotransmitter in the central nervous system, it is also the most common excitotoxicity trigger. This uncontrolled neuronal response participates in various neurodegenerative diseases, such as ischemia, hypoglycemia, Huntington’s, Parkinson’s and Alzheimer’s disease. Thus, the investigation in the field expanded a lot in the past decade, leading to in vitro modelling adaptations. However, much performed work on glutamate-induced excitotoxicity is methodologically inconsistent in the literature. The field lacks reproducibility, which is one of the main fundaments of empirical science. In this regard, the literature was summarized and the main methodological features were critically evaluated, aiming to gui
Methods:
Published data since 1985 from PUBMED were collected and analyzed to observe which in vitro experimental conditions of excitotoxicity were reproducible. The suggested methods were based on the characteristics of excitotoxicity, such as abnormal intracellular calcium mediated signaling, mitochondria impairment, reactive oxygen species accumulation and cell death. Various conditions and comparative controls were used to design the standard investigation of excitotoxicity, such as culture medium content (presence of glutamate and aspartate), time interval of induction and the concentration of the inductor, based on the most reproducible published ones.
Results:
Our results and critical analysis point to some experimental conditions to consider, such as primary cultured neurons are more sensitive to glutamate and the response obtained is more robust than in other models; excitotoxicity mediated effects are better observed one hour following the stimulus; the culture medium should contain low levels of glutamate or aspartate or glycine. Online available phosphoproteomic data on excitotoxicity using the primary cortical neurons in vitro model supported the same conditions proposed by us.
Conclusions:
This manuscript will facilitate the design of any research for excitotoxic or neuroprotective compounds in physiological and pathophysiological conditions by standardizing and improving experimental conditions.
DOI: https://doi.org/10.37349/ent.2022.00017
Aim:
Although the prevalence of coronary heart disease (CHD) and hypertension which are the most common causes of the development and progression of chronic heart failure (CHF) is high, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) in patients with CHF is not mandatory to be performed. The growing number of evidence suggests that excessive decrease in BP which clearly reflects increased BP variability (BPV) affects the survival of patients with heart failure (HF). The objective of the study was to investigate the relationship between the parameters specific to CHF severity and features of daily BP profiles in patients with ischemic CHF and hypertension.
Methods:
Ninety patients with functional class II–IV of CHF and CHD (the main group) and 50 non-CHF patients with hypertension (the comparative group) were examined. The transthoracic echocardiography (TTE) [atrial end-systolic dimension (ESD), ventricular end-diastolic dimension (EDD), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF)] and 24-hour ABPM (BPV parameters and proportions of hypotensive episodes) were performed. The relationships between the abovementioned parameters were evaluated using the univariate correlation analysis and stepwise multiple linear regression.
Results:
Higher functional class of CHF is found to be associated with a higher incidence of daytime systolic BP (SBP) decline and nighttime SBP and diastolic BP (DBP) variability while higher LVEF is related to the hypotensive episodes regardless of CHF.
Conclusions:
It appears that the larger trials involving CHF patients with reduced LVEF should be conducted to clarify the obtained results.
Aim:
Although the prevalence of coronary heart disease (CHD) and hypertension which are the most common causes of the development and progression of chronic heart failure (CHF) is high, 24-hour ambulatory blood pressure (BP) monitoring (ABPM) in patients with CHF is not mandatory to be performed. The growing number of evidence suggests that excessive decrease in BP which clearly reflects increased BP variability (BPV) affects the survival of patients with heart failure (HF). The objective of the study was to investigate the relationship between the parameters specific to CHF severity and features of daily BP profiles in patients with ischemic CHF and hypertension.
Methods:
Ninety patients with functional class II–IV of CHF and CHD (the main group) and 50 non-CHF patients with hypertension (the comparative group) were examined. The transthoracic echocardiography (TTE) [atrial end-systolic dimension (ESD), ventricular end-diastolic dimension (EDD), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF)] and 24-hour ABPM (BPV parameters and proportions of hypotensive episodes) were performed. The relationships between the abovementioned parameters were evaluated using the univariate correlation analysis and stepwise multiple linear regression.
Results:
Higher functional class of CHF is found to be associated with a higher incidence of daytime systolic BP (SBP) decline and nighttime SBP and diastolic BP (DBP) variability while higher LVEF is related to the hypotensive episodes regardless of CHF.
Conclusions:
It appears that the larger trials involving CHF patients with reduced LVEF should be conducted to clarify the obtained results.
DOI: https://doi.org/10.37349/emed.2024.00209
Aim:
The present study investigates the influence of various homogenization techniques, namely high-pressure valve homogenization and microfluidization, and different forms of modified sunflower lecithin, including deoiled (DL) and hydrolyzed (HL) variants, on the development of monolayer and bilayer nanoemulsions of chia oil.
Methods:
Oil-in-water (O/W) nanoemulsions with 5% chia seed oil were prepared using simple (0.5% DL or HL) or double-layer [0.5% DL or HL and 0.3% chitosan (Ch)] stabilization. This involved a two-step homogenization process, utilizing either microfluidization or high-pressure valve homogenization. Chia oil nanoemulsions were characterized by their zeta potential, particle size, and rheological properties. Besides, their physical stability and omega-3 content during refrigerated storage were evaluated.
Results:
Overall, the studied modified sunflower lecithin (DL and HL) demonstrated effective capability in stabilizing chia nanoemulsions and facilitating the formation of the double-layered structure following Ch deposition. Concerning the homogenization method, it has been demonstrated that under the same homogenization conditions, microfluidization resulted in significantly smaller droplet sizes and higher apparent viscosities compared to high-pressure valve homogenization. This discrepancy can be attributed to the design of the homogenization chambers, as microfluidization generates a narrow distribution of shear forces, while high-pressure valve homogenization yields a much broader distribution. In contrast to chia monolayer nanoemulsions, the nanoemulsions stabilized by modified sunflower lecithin-Ch demonstrated a noteworthy improvement in their overall stability. This enhancement can be ascribed to their increased apparent viscosity and the highly charged interfaces of the droplets. Furthermore, throughout the entire refrigerated storage period, the omega-3 content in all nanoemulsions remained unchanged.
Conclusions:
In this study, mono and bilayer chia oil nanoemulsions were successfully obtained using modified sunflower lecithin and high-energy techniques. Microfluidization outperformed high-pressure valve homogenization, resulting in smaller droplets and increased viscosity. These findings are relevant for designing stable chia oil nanoemulsions with natural components, offering substantial health benefits.
Aim:
The present study investigates the influence of various homogenization techniques, namely high-pressure valve homogenization and microfluidization, and different forms of modified sunflower lecithin, including deoiled (DL) and hydrolyzed (HL) variants, on the development of monolayer and bilayer nanoemulsions of chia oil.
Methods:
Oil-in-water (O/W) nanoemulsions with 5% chia seed oil were prepared using simple (0.5% DL or HL) or double-layer [0.5% DL or HL and 0.3% chitosan (Ch)] stabilization. This involved a two-step homogenization process, utilizing either microfluidization or high-pressure valve homogenization. Chia oil nanoemulsions were characterized by their zeta potential, particle size, and rheological properties. Besides, their physical stability and omega-3 content during refrigerated storage were evaluated.
Results:
Overall, the studied modified sunflower lecithin (DL and HL) demonstrated effective capability in stabilizing chia nanoemulsions and facilitating the formation of the double-layered structure following Ch deposition. Concerning the homogenization method, it has been demonstrated that under the same homogenization conditions, microfluidization resulted in significantly smaller droplet sizes and higher apparent viscosities compared to high-pressure valve homogenization. This discrepancy can be attributed to the design of the homogenization chambers, as microfluidization generates a narrow distribution of shear forces, while high-pressure valve homogenization yields a much broader distribution. In contrast to chia monolayer nanoemulsions, the nanoemulsions stabilized by modified sunflower lecithin-Ch demonstrated a noteworthy improvement in their overall stability. This enhancement can be ascribed to their increased apparent viscosity and the highly charged interfaces of the droplets. Furthermore, throughout the entire refrigerated storage period, the omega-3 content in all nanoemulsions remained unchanged.
Conclusions:
In this study, mono and bilayer chia oil nanoemulsions were successfully obtained using modified sunflower lecithin and high-energy techniques. Microfluidization outperformed high-pressure valve homogenization, resulting in smaller droplets and increased viscosity. These findings are relevant for designing stable chia oil nanoemulsions with natural components, offering substantial health benefits.
DOI: https://doi.org/10.37349/eff.2024.00029
This article belongs to the special issue Delivery of Hydrophobic Compounds in Food Systems
Aim:
Aloysia citrodora has a long history of traditional use in treating various ailments. This study evaluated the in vivo chemopreventive efficacy and systemic toxicity of an extract of A. citrodora in a transgenic mouse model of HPV16 (human papillomavirus type 16)-induced cancer.
Methods:
The experiment involved six groups (n = 5): group 1 (G1, wild-type (WT), water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.013 g/mL), group 4 (G4, HPV, 0.006 g/mL), group 5 (G5, HPV, 0.008 g/mL), and group 6 (G6, HPV, 0.013 g/mL). Throughout the assay, humane endpoints, body weight, food, and water consumption were recorded weekly. The internal organs and skin of the mice were collected for analysis after they were sacrificed. Toxicological parameters that were studied included hematological and biochemical blood markers, splenic and hepatic histology, and hepatic oxidative stress.
Results:
A. citrodora extract seems to reduce the incidence of dysplastic and in situ carcinoma skin lesions induced by HPV16 in this model, suggesting that dietary supplementation with concentrations of 0.008 g/mL and 0.013 g/mL may have beneficial chemopreventive effects.
Conclusions:
The extract did not induce any concentration-dependent toxicological effects on any of the parameters included in the study, indicating a favorable toxicological profile under these experimental conditions.
Aim:
Aloysia citrodora has a long history of traditional use in treating various ailments. This study evaluated the in vivo chemopreventive efficacy and systemic toxicity of an extract of A. citrodora in a transgenic mouse model of HPV16 (human papillomavirus type 16)-induced cancer.
Methods:
The experiment involved six groups (n = 5): group 1 (G1, wild-type (WT), water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.013 g/mL), group 4 (G4, HPV, 0.006 g/mL), group 5 (G5, HPV, 0.008 g/mL), and group 6 (G6, HPV, 0.013 g/mL). Throughout the assay, humane endpoints, body weight, food, and water consumption were recorded weekly. The internal organs and skin of the mice were collected for analysis after they were sacrificed. Toxicological parameters that were studied included hematological and biochemical blood markers, splenic and hepatic histology, and hepatic oxidative stress.
Results:
A. citrodora extract seems to reduce the incidence of dysplastic and in situ carcinoma skin lesions induced by HPV16 in this model, suggesting that dietary supplementation with concentrations of 0.008 g/mL and 0.013 g/mL may have beneficial chemopreventive effects.
Conclusions:
The extract did not induce any concentration-dependent toxicological effects on any of the parameters included in the study, indicating a favorable toxicological profile under these experimental conditions.
DOI: https://doi.org/10.37349/emed.2024.00228
Aim:
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.
Methods:
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
Results:
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
Conclusions:
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.
Aim:
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.
Methods:
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
Results:
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
Conclusions:
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.
DOI: https://doi.org/10.37349/edd.2023.00033
This article belongs to the special issue Helicobacter Pylori and Infection: Genomics, Diagnosis, Pathogenesis, Antibiotic Resistance, Microbiota, Cancer, Prevention and Therapeutics
Aim:
Breast cancer (BC) is the most common cancer in women worldwide, where adiposity has been linked to BC morbidity. In general, obese premenopausal women diagnosed with
Methods:
Adipocytes were cultured with and without Matrigel, where semi-quantitative proteomics was used to identify proteins whose presence in the CM was induced or enhanced by Matrigel, which were referred to as adipocyte-secreted ECM-induced proteins (AEPs). The AEPs identified were assessed for association with prognosis in published proteomic datasets and prior literature. Of these, 4 were evaluated by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), followed by a functional and MET marker analysis of 1 AEP on MDA-MB-231 cells grown on Matrigel or as monolayers.
Results:
The 4 AEPs showed a positive correlation between protein expression and poor prognosis. RT-qPCR analysis reported no significant change in AEPs mRNA expression. However, lysyl oxidase (LOX) was increased in CM of ECM-exposed adipocytes. Recombinant LOX (rLOX) caused the mesenchymal MDA-MB-231 TNBC cells to form less branched 3D structures and reduced the expression of vimentin.
Conclusions:
The data suggest that adipocyte-secreted LOX changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumour formation, particularly at sites high in adipocytes such as the bone marrow. Future efforts should focus on determining whether targeting LOX could reduce BC metastasis in obese individuals.
Aim:
Breast cancer (BC) is the most common cancer in women worldwide, where adiposity has been linked to BC morbidity. In general, obese premenopausal women diagnosed with
Methods:
Adipocytes were cultured with and without Matrigel, where semi-quantitative proteomics was used to identify proteins whose presence in the CM was induced or enhanced by Matrigel, which were referred to as adipocyte-secreted ECM-induced proteins (AEPs). The AEPs identified were assessed for association with prognosis in published proteomic datasets and prior literature. Of these, 4 were evaluated by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), followed by a functional and MET marker analysis of 1 AEP on MDA-MB-231 cells grown on Matrigel or as monolayers.
Results:
The 4 AEPs showed a positive correlation between protein expression and poor prognosis. RT-qPCR analysis reported no significant change in AEPs mRNA expression. However, lysyl oxidase (LOX) was increased in CM of ECM-exposed adipocytes. Recombinant LOX (rLOX) caused the mesenchymal MDA-MB-231 TNBC cells to form less branched 3D structures and reduced the expression of vimentin.
Conclusions:
The data suggest that adipocyte-secreted LOX changes the mesenchymal phenotype of BC cells in a manner that could promote secondary tumour formation, particularly at sites high in adipocytes such as the bone marrow. Future efforts should focus on determining whether targeting LOX could reduce BC metastasis in obese individuals.
DOI: https://doi.org/10.37349/etat.2024.00201
This article belongs to the special issue Innovative Strategies to Target Triple-negative Breast Cancer
Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provi
Breast cancer (BC) is the most prevalent malignancy affecting women worldwide, including Portugal. While the majority of BC cases are sporadic, hereditary forms account for 5-10% of cases. The most common inherited mutations associated with BC are germline mutations in the BReast CAncer (BRCA) 1/2 gene (gBRCA1/2). They are found in approximately 5-6% of BC patients and are inherited in an autosomal dominant manner, primarily affecting younger women. Pathogenic variants within BRCA1/2 genes elevate the risk of both breast and ovarian cancers and give rise to distinct clinical phenotypes. BRCA proteins play a key role in maintaining genome integrity by facilitating the repair of double-strand breaks through the homologous recombination (HR) pathway. Therefore, any mutation that impairs the function of BRCA proteins can result in the accumulation of DNA damage, genomic instability, and potentially contribute to cancer development and progression. Testing for gBRCA1/2 status is relevant for treatment planning, as it can provi
DOI: https://doi.org/10.37349/etat.2024.00241
Aim:
The aim of this study is to apply untargeted proton nuclear magnetic resonance (1H NMR) and chemometric analysis to obtain the cacao pod husk (CPH) fingerprint and evaluate the effect of dehydration in the CPH metabolome.
Methods:
Phosphate buffer extracts (pH 6.5) were obtained and measured using a one-dimension (1D) 1H NMR spectrometry. The 1D 1H NMR spectra were recorded without spinning and using the presaturation (PRESAT) pulse sequence to suppress the residual H2O signal. The 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid sodium salt (TSP) was used as an internal reference. Analysis of processed data, applying an orthogonal projection on latent structure-discriminant analysis (OPLS-DA) model was used to highlight significant differences between the three dehydration treatments. Signal assignment of CPH metabolites was carried out based on the coupling constant, software simulation prediction, published data comparison, and metabolomics databases.
Results:
A total of 25 compounds were detected by 1H NMR, methylxanthines, sugars, some amino acids, fatty acids, and organic acids were found among the identified compounds. The fingerprint spectra of the three dehydration methods were clustered separately discriminating the metabolome profile of each of the dehydration treatments, finding that metabolome remarkably differed in theanine, myristic acid, fumaric acid, and aspartic acid composition.
Conclusions:
An untargeted metabolomics to obtain the fingerprint of CPH was successfully established. A 1H NMR spectra with a detailed signal assignment aided to identify 25 metabolites present in CPH fresh and dried by different methods. The results complement the information about CPH composition and how it is affected by the temperature used during the dehydration process. The multivariate analysis points out that freeze drying (FD) preserves the metabolites better than microwave drying (MWD) or hot air drying (HAD). FD and MWD are similar in composition maintaining most of the compounds after drying.
Aim:
The aim of this study is to apply untargeted proton nuclear magnetic resonance (1H NMR) and chemometric analysis to obtain the cacao pod husk (CPH) fingerprint and evaluate the effect of dehydration in the CPH metabolome.
Methods:
Phosphate buffer extracts (pH 6.5) were obtained and measured using a one-dimension (1D) 1H NMR spectrometry. The 1D 1H NMR spectra were recorded without spinning and using the presaturation (PRESAT) pulse sequence to suppress the residual H2O signal. The 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid sodium salt (TSP) was used as an internal reference. Analysis of processed data, applying an orthogonal projection on latent structure-discriminant analysis (OPLS-DA) model was used to highlight significant differences between the three dehydration treatments. Signal assignment of CPH metabolites was carried out based on the coupling constant, software simulation prediction, published data comparison, and metabolomics databases.
Results:
A total of 25 compounds were detected by 1H NMR, methylxanthines, sugars, some amino acids, fatty acids, and organic acids were found among the identified compounds. The fingerprint spectra of the three dehydration methods were clustered separately discriminating the metabolome profile of each of the dehydration treatments, finding that metabolome remarkably differed in theanine, myristic acid, fumaric acid, and aspartic acid composition.
Conclusions:
An untargeted metabolomics to obtain the fingerprint of CPH was successfully established. A 1H NMR spectra with a detailed signal assignment aided to identify 25 metabolites present in CPH fresh and dried by different methods. The results complement the information about CPH composition and how it is affected by the temperature used during the dehydration process. The multivariate analysis points out that freeze drying (FD) preserves the metabolites better than microwave drying (MWD) or hot air drying (HAD). FD and MWD are similar in composition maintaining most of the compounds after drying.
DOI: https://doi.org/10.37349/eff.2023.00009
Aim:
To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD).
Methods:
From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay.
Results:
A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment.
Conclusions:
VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).
Aim:
To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD).
Methods:
From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay.
Results:
A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment.
Conclusions:
VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).
DOI: https://doi.org/10.37349/emed.2023.00137
This article belongs to the special issue Lung Fibrosis—Models and Mechanisms
