Previous
Virtual reality (VR) and digital health technologies have shown increasing potential in addressing psychological challenges such as homesickness and emotional distress, yet the role of emotional bonds, particularly place attachment, in shaping the design and effectiveness of these interventions remains underexplored. This study conceptualizes the integration of place attachment theory into digital health interventions, especially those utilizing VR, and proposes a theoretical and practical framework for designing emotionally resonant virtual environments. Two interrelated conceptual models are introduced: the Virtual Place Attachment Development Model (VPADM), which outlines psychological, social, environmental, and cultural dimensions that contribute to emotional bonding with virtual spaces, and the Cultural Adaptation System for Virtual Environments (CASVE), which addresses cross-cultural adaptation processes through assessment, implementation, and evaluation. These frameworks illustrate how virtual place attachment can be purposefully designed to enhance user engagement and emotional well-being, while also highlighting practical challenges such as accessibility, digital literacy, and the need for culturally responsive content. By integrating place attachment theory into digital mental health design, the paper offers a pathway to improve therapeutic outcomes in VR environments and provides a foundation for researchers and practitioners to develop emotionally supportive, culturally meaningful, and context-sensitive digital health interventions.
Virtual reality (VR) and digital health technologies have shown increasing potential in addressing psychological challenges such as homesickness and emotional distress, yet the role of emotional bonds, particularly place attachment, in shaping the design and effectiveness of these interventions remains underexplored. This study conceptualizes the integration of place attachment theory into digital health interventions, especially those utilizing VR, and proposes a theoretical and practical framework for designing emotionally resonant virtual environments. Two interrelated conceptual models are introduced: the Virtual Place Attachment Development Model (VPADM), which outlines psychological, social, environmental, and cultural dimensions that contribute to emotional bonding with virtual spaces, and the Cultural Adaptation System for Virtual Environments (CASVE), which addresses cross-cultural adaptation processes through assessment, implementation, and evaluation. These frameworks illustrate how virtual place attachment can be purposefully designed to enhance user engagement and emotional well-being, while also highlighting practical challenges such as accessibility, digital literacy, and the need for culturally responsive content. By integrating place attachment theory into digital mental health design, the paper offers a pathway to improve therapeutic outcomes in VR environments and provides a foundation for researchers and practitioners to develop emotionally supportive, culturally meaningful, and context-sensitive digital health interventions.
DOI: https://doi.org/10.37349/edht.2025.101160
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more rapidly progressive variant steatohepatitis (MASH) are widespread chronic liver conditions linked to obesity and other common metabolic disorders. The emergence of tirzepatide, a dual incretin receptor agonist targeting both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, presents major therapeutic potential for MASLD. This review article explores the mechanisms of action of tirzepatide, highlighting its ability to improve glycemic control, promote weight loss, and potentially ameliorate hepatic steatosis and fibrosis. Recent studies suggest that tirzepatide may offer significant benefits in managing MASLD/MASH by modulating metabolic pathways and enhancing liver health. However, further research is needed to fully understand its long-term impact on MASLD/MASH progression and outcomes across diverse patient populations.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more rapidly progressive variant steatohepatitis (MASH) are widespread chronic liver conditions linked to obesity and other common metabolic disorders. The emergence of tirzepatide, a dual incretin receptor agonist targeting both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, presents major therapeutic potential for MASLD. This review article explores the mechanisms of action of tirzepatide, highlighting its ability to improve glycemic control, promote weight loss, and potentially ameliorate hepatic steatosis and fibrosis. Recent studies suggest that tirzepatide may offer significant benefits in managing MASLD/MASH by modulating metabolic pathways and enhancing liver health. However, further research is needed to fully understand its long-term impact on MASLD/MASH progression and outcomes across diverse patient populations.
DOI: https://doi.org/10.37349/eds.2025.1008128
Aim:
Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats.
Methods:
Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate.
Results:
It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p < 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease (p < 0.01) in malondialdehyde level and an increase (p < 0.05) in reduced glutathione level.
Conclusions:
These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action.
Aim:
Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats.
Methods:
Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate.
Results:
It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p < 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease (p < 0.01) in malondialdehyde level and an increase (p < 0.05) in reduced glutathione level.
Conclusions:
These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action.
DOI: https://doi.org/10.37349/eds.2025.1008127
Peroxisome proliferator-activated receptors (PPARs) comprise three isoforms: PPARα, PPARβ/δ, and PPARγ, which regulate the expression of genes involved in fatty acid uptake, β-oxidation, adipogenesis, gluconeogenesis, and insulin sensitivity. Type 2 diabetes (T2D), often accompanied by other features of metabolic syndrome, contributes to vasculopathy, end-stage organ failure, and cancer. Metabolic dysfunction-associated steatotic liver disease (MASLD) refers to steatotic liver disease in the presence of cardiometabolic risk factor(s) and without excessive alcohol consumption. MASLD is prevalent among adults with T2D and carries a high risk of liver fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis and incident T2D. In MASLD, the liver becomes a hub of lipid toxicity, oxidative stress, and fibrotic signalling whenever T2D disrupts hormonal and adipokine signalling, increases free fatty acid flux, and promotes chronic inflammation. MASLD, therefore, results from an impairment of the protection physiologically offered by PPARs through fatty acid oxidation, lipid storage in the adipose tissue, and mitigation of insulin resistance and pro-inflammatory cascades. By examining the molecular mechanisms of PPARα, PPARβ/δ, and PPARγ, as well as their interactions with cofactors like PGC-1α, and their crosstalk with pathways like sterol regulatory element-binding protein (SREBP), NF-κB, AMP-activated protein kinase (AMPK), and adipokines, researchers and clinicians can better understand how T2D-related MASLD can be prevented or treated. Single PPAR agonists, such as fibrates and glitazones, have limited clinical efficacy in achieving hard liver histology endpoints like MASH resolution and fibrosis regression in humans. However, the Pan-PPAR agonist Lanifibranor at the highest doses shows promise in ameliorating these outcomes in subjects with non-cirrhotic MASH. This suggests that activating all three PPAR isoforms together enhances their therapeutic effects on various cells and target organs, restoring insulin resistance, improving gluco-lipidic homeostasis, while inhibiting pro-inflammatory and pro-fibrogenic pathways. Analysis of unresolved issues should dictate the research agenda.
Peroxisome proliferator-activated receptors (PPARs) comprise three isoforms: PPARα, PPARβ/δ, and PPARγ, which regulate the expression of genes involved in fatty acid uptake, β-oxidation, adipogenesis, gluconeogenesis, and insulin sensitivity. Type 2 diabetes (T2D), often accompanied by other features of metabolic syndrome, contributes to vasculopathy, end-stage organ failure, and cancer. Metabolic dysfunction-associated steatotic liver disease (MASLD) refers to steatotic liver disease in the presence of cardiometabolic risk factor(s) and without excessive alcohol consumption. MASLD is prevalent among adults with T2D and carries a high risk of liver fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis and incident T2D. In MASLD, the liver becomes a hub of lipid toxicity, oxidative stress, and fibrotic signalling whenever T2D disrupts hormonal and adipokine signalling, increases free fatty acid flux, and promotes chronic inflammation. MASLD, therefore, results from an impairment of the protection physiologically offered by PPARs through fatty acid oxidation, lipid storage in the adipose tissue, and mitigation of insulin resistance and pro-inflammatory cascades. By examining the molecular mechanisms of PPARα, PPARβ/δ, and PPARγ, as well as their interactions with cofactors like PGC-1α, and their crosstalk with pathways like sterol regulatory element-binding protein (SREBP), NF-κB, AMP-activated protein kinase (AMPK), and adipokines, researchers and clinicians can better understand how T2D-related MASLD can be prevented or treated. Single PPAR agonists, such as fibrates and glitazones, have limited clinical efficacy in achieving hard liver histology endpoints like MASH resolution and fibrosis regression in humans. However, the Pan-PPAR agonist Lanifibranor at the highest doses shows promise in ameliorating these outcomes in subjects with non-cirrhotic MASH. This suggests that activating all three PPAR isoforms together enhances their therapeutic effects on various cells and target organs, restoring insulin resistance, improving gluco-lipidic homeostasis, while inhibiting pro-inflammatory and pro-fibrogenic pathways. Analysis of unresolved issues should dictate the research agenda.
DOI: https://doi.org/10.37349/edd.2025.100590
This article belongs to the special issue Nuclear Receptors and the Digestive Tract: from Molecular Physiology to Clinics via Pharmacology
Patients who have lupus nephritis are usually asymptomatic. A few lupus nephritis patients may experience edema, hypertension, nocturia, polyuria, and foamy urine. Foamy urine or nocturia are early indicators of proteinuria, indicating tubular or glomerular dysfunction. Membranous-like glomerulopathy with masked IgG kappa deposits (MMMD) represents a form of immune complex deposition marked by concealed IgG kappa-restricted deposits, which are located in the subepithelial and mesangial areas as seen on electron microscopy. We report a rare case of a 26-year-old Hispanic woman with a history of systemic lupus erythematosus (SLE) diagnosed in 2015, who was initially evaluated for proteinuria and underwent a renal biopsy in 2019. The biopsy demonstrated membranous glomerulonephritis consistent with class V lupus nephritis. The patient volunteered to participate in a clinical trial for lupus nephritis in mid-2023. The second renal biopsy done at this visit (4 years after the initial renal biopsy) reported membranous glomerulonephritis, consistent with lupus class V and MMMD. Given the new finding of MMMD, a search for monoclonal gammopathy was initiated by looking for flow cytometry, serum protein electrophoresis (SPEP), and serum-free light chains, all of which were reported as negative. As the workup for monoclonal gammopathy and monoclonal gammopathy of renal significance (MGRS) was negative, MMMD was considered a secondary manifestation of lupus nephritis, a rare renal presentation of the condition.
Patients who have lupus nephritis are usually asymptomatic. A few lupus nephritis patients may experience edema, hypertension, nocturia, polyuria, and foamy urine. Foamy urine or nocturia are early indicators of proteinuria, indicating tubular or glomerular dysfunction. Membranous-like glomerulopathy with masked IgG kappa deposits (MMMD) represents a form of immune complex deposition marked by concealed IgG kappa-restricted deposits, which are located in the subepithelial and mesangial areas as seen on electron microscopy. We report a rare case of a 26-year-old Hispanic woman with a history of systemic lupus erythematosus (SLE) diagnosed in 2015, who was initially evaluated for proteinuria and underwent a renal biopsy in 2019. The biopsy demonstrated membranous glomerulonephritis consistent with class V lupus nephritis. The patient volunteered to participate in a clinical trial for lupus nephritis in mid-2023. The second renal biopsy done at this visit (4 years after the initial renal biopsy) reported membranous glomerulonephritis, consistent with lupus class V and MMMD. Given the new finding of MMMD, a search for monoclonal gammopathy was initiated by looking for flow cytometry, serum protein electrophoresis (SPEP), and serum-free light chains, all of which were reported as negative. As the workup for monoclonal gammopathy and monoclonal gammopathy of renal significance (MGRS) was negative, MMMD was considered a secondary manifestation of lupus nephritis, a rare renal presentation of the condition.
DOI: https://doi.org/10.37349/emed.2025.1001353
This review presents key molecular biology techniques used to investigate interactions between biomaterials and biological systems, emphasizing their role in evaluating biocompatibility and cellular responses. We focus on methodologies such as recombinant DNA technology, polymerase chain reaction (PCR), in situ hybridization, immunocytochemistry (ICC), and immunohistochemistry (IHC). These tools enable the detection and quantification of gene and protein expression, particularly those involved in inflammation and tissue regeneration, providing molecular-level insights into how cells respond to biomaterial cues. We discuss the relevance of these techniques in identifying inflammatory markers, tracking cell differentiation, and understanding tissue integration processes, as well as how their implementation faces technical challenges, including interference from the physicochemical properties of biomaterials, difficulties in sample preparation, and the standardization of protocols across different platforms. Addressing these limitations is vital to ensure data reliability and reproducibility. Looking ahead, we highlight emerging opportunities involving the integration of 3D imaging technologies and artificial intelligence to manage and interpret high-dimensional biological data. This article also serves as a practical tool for emerging investigators who are entering the field of biomaterials, offering accessible guidance on the selection and application of essential molecular biology techniques. These innovations promise to accelerate the rational design of biomaterials tailored to specific clinical applications and patient needs. In conclusion, molecular biology techniques provide a foundational toolkit for characterizing biological responses to biomaterials, supporting the development of safer and more effective therapeutic materials and empowering emerging investigators to contribute meaningfully to the next generation of biomedical solutions.
This review presents key molecular biology techniques used to investigate interactions between biomaterials and biological systems, emphasizing their role in evaluating biocompatibility and cellular responses. We focus on methodologies such as recombinant DNA technology, polymerase chain reaction (PCR), in situ hybridization, immunocytochemistry (ICC), and immunohistochemistry (IHC). These tools enable the detection and quantification of gene and protein expression, particularly those involved in inflammation and tissue regeneration, providing molecular-level insights into how cells respond to biomaterial cues. We discuss the relevance of these techniques in identifying inflammatory markers, tracking cell differentiation, and understanding tissue integration processes, as well as how their implementation faces technical challenges, including interference from the physicochemical properties of biomaterials, difficulties in sample preparation, and the standardization of protocols across different platforms. Addressing these limitations is vital to ensure data reliability and reproducibility. Looking ahead, we highlight emerging opportunities involving the integration of 3D imaging technologies and artificial intelligence to manage and interpret high-dimensional biological data. This article also serves as a practical tool for emerging investigators who are entering the field of biomaterials, offering accessible guidance on the selection and application of essential molecular biology techniques. These innovations promise to accelerate the rational design of biomaterials tailored to specific clinical applications and patient needs. In conclusion, molecular biology techniques provide a foundational toolkit for characterizing biological responses to biomaterials, supporting the development of safer and more effective therapeutic materials and empowering emerging investigators to contribute meaningfully to the next generation of biomedical solutions.
DOI: https://doi.org/10.37349/ebmx.2025.101344
O6-Methylguanine-DNA methyltransferase (MGMT) acts as a genomic custodian, reversing alkylation damage to preserve DNA integrity. However, when its regulatory balance tips via promoter methylation, polymorphisms, or epigenetic silencing, MGMT can become a liability, fuelling cancer progression, treatment resistance, and poor outcomes across malignancies. This review uncovers the nuanced control of MGMT, revealing how its genetic and epigenetic shifts shape tumor behavior, therapeutic response, and risk stratification. We aim to transform molecular insights into actionable clinical strategies, reimagining MGMT as both a biomarker and therapeutic lever. We curated high-impact studies (up to 2025) from PubMed, Scopus, and Web of Science, focusing on MGMT modulation, synthetic lethality, CRISPR-based restoration, and epigenetic therapies. Emerging multi-omics and translational frameworks were prioritized. MGMT’s activity is choreographed by an intricate interplay of promoter methylation, histone marks, transcriptional regulation, and microRNA influence. These dynamics critically affect sensitivity to alkylating agents like temozolomide. Intriguingly, MGMT also engages with the immune landscape modulating response to immunotherapies. Innovations in multi-omics, single-cell analytics, and AI-based biomarker profiling are unveiling previously hidden regulatory layers. Decoding MGMT’s regulation unlocks new therapeutic frontiers. Cutting-edge strategies from CRISPR to liquid biopsy promise more personalized, resistance-proof cancer care.
O6-Methylguanine-DNA methyltransferase (MGMT) acts as a genomic custodian, reversing alkylation damage to preserve DNA integrity. However, when its regulatory balance tips via promoter methylation, polymorphisms, or epigenetic silencing, MGMT can become a liability, fuelling cancer progression, treatment resistance, and poor outcomes across malignancies. This review uncovers the nuanced control of MGMT, revealing how its genetic and epigenetic shifts shape tumor behavior, therapeutic response, and risk stratification. We aim to transform molecular insights into actionable clinical strategies, reimagining MGMT as both a biomarker and therapeutic lever. We curated high-impact studies (up to 2025) from PubMed, Scopus, and Web of Science, focusing on MGMT modulation, synthetic lethality, CRISPR-based restoration, and epigenetic therapies. Emerging multi-omics and translational frameworks were prioritized. MGMT’s activity is choreographed by an intricate interplay of promoter methylation, histone marks, transcriptional regulation, and microRNA influence. These dynamics critically affect sensitivity to alkylating agents like temozolomide. Intriguingly, MGMT also engages with the immune landscape modulating response to immunotherapies. Innovations in multi-omics, single-cell analytics, and AI-based biomarker profiling are unveiling previously hidden regulatory layers. Decoding MGMT’s regulation unlocks new therapeutic frontiers. Cutting-edge strategies from CRISPR to liquid biopsy promise more personalized, resistance-proof cancer care.
DOI: https://doi.org/10.37349/etat.2025.1002335
This article belongs to the special issue Advances in Cancer Genomics and Therapeutic Targets
Cancer is the second leading cause of death globally and in the United States, second only to cardiovascular disease. Unlike many cardiovascular conditions, cancer is often less preventable, manageable, and curable—even with ongoing technological advancements in medicine. The adverse effects of cancer treatments on cancer patients remain profound due to shared cellular characteristics between cancerous and normal cells; one of the primary adverse effects is treatment-induced inflammation. These inflammatory responses aim to eliminate cancerous cells but often damage normal tissues. Notably, inflammatory side effects vary considerably across the growing diversity of therapeutic approaches. This study reviewed studies between 2007 and 2024, comparing the inflammatory profiles associated with five major radiation therapies (RTs): Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation Therapy (IGRT), Stereotactic Body Radiation Therapy (SBRT), and Proton Beam Therapy (PBT)—each characterized by distinct mechanistic and therapeutic features. In addition to each radiation modality eliciting distinct inflammatory responses, tissue-specific variability further complicates clinical outcomes. Accordingly, this review also undertakes a cross-tissue comparison of radiation-induced inflammation, with a focus on the gastrointestinal (GI) system, central nervous system (CNS), and skin. However, the variation in treatment modalities and organ-specific inflammatory biomarkers greatly hinders direct comparison across studies. Finally, this review highlights potential inflammatory mitigations, including ambroxol, that may be employed synergistically with RTs, minimizing side effects and enhancing patient outcomes. Taken together, while all modalities offer therapeutic value alongside certain limitations, proton-based therapy demonstrates the greatest potential for minimizing toxicity though its broader adoption remains limited by cost-effectiveness concerns.
Cancer is the second leading cause of death globally and in the United States, second only to cardiovascular disease. Unlike many cardiovascular conditions, cancer is often less preventable, manageable, and curable—even with ongoing technological advancements in medicine. The adverse effects of cancer treatments on cancer patients remain profound due to shared cellular characteristics between cancerous and normal cells; one of the primary adverse effects is treatment-induced inflammation. These inflammatory responses aim to eliminate cancerous cells but often damage normal tissues. Notably, inflammatory side effects vary considerably across the growing diversity of therapeutic approaches. This study reviewed studies between 2007 and 2024, comparing the inflammatory profiles associated with five major radiation therapies (RTs): Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation Therapy (IGRT), Stereotactic Body Radiation Therapy (SBRT), and Proton Beam Therapy (PBT)—each characterized by distinct mechanistic and therapeutic features. In addition to each radiation modality eliciting distinct inflammatory responses, tissue-specific variability further complicates clinical outcomes. Accordingly, this review also undertakes a cross-tissue comparison of radiation-induced inflammation, with a focus on the gastrointestinal (GI) system, central nervous system (CNS), and skin. However, the variation in treatment modalities and organ-specific inflammatory biomarkers greatly hinders direct comparison across studies. Finally, this review highlights potential inflammatory mitigations, including ambroxol, that may be employed synergistically with RTs, minimizing side effects and enhancing patient outcomes. Taken together, while all modalities offer therapeutic value alongside certain limitations, proton-based therapy demonstrates the greatest potential for minimizing toxicity though its broader adoption remains limited by cost-effectiveness concerns.
DOI: https://doi.org/10.37349/etat.2025.1002334
Gout is a chronic inflammatory arthritis driven by monosodium urate crystal deposition and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation, leading to interleukin-1β (IL-1β)-mediated inflammation. Recent studies reveal that hyperuricemia induces a state of immunological memory in innate immune cells through persistent epigenetic and metabolic reprogramming of monocytes and macrophages. These alterations enhance the responsiveness of innate immune cells, leading to exaggerated inflammatory reactions upon subsequent stimulation. This review synthesizes recent studies that elucidate how metabolic shifts (e.g., increased glycolysis and fumarate accumulation) and epigenetic changes (e.g., altered histone methylation and DNA methylation) reinforce this pathogenic memory. Importantly, these mechanistic insights provide the rationale for emerging therapeutic strategies: IL-1β inhibitors aim to interrupt the central inflammatory axis; metabolic modulators (e.g., metformin, statins) seek to reverse the trained metabolic state; and epigenetic therapies [e.g., histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors] hold potential to reset dysregulated immune programming. Collectively, this review argues that multi-layered intervention, such as cytokine blockade for acute control, coupled with metabolic or epigenetic remodeling for long-term reprogramming, could yield sustained disease suppression and reduced flare frequency in gout.
Gout is a chronic inflammatory arthritis driven by monosodium urate crystal deposition and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation, leading to interleukin-1β (IL-1β)-mediated inflammation. Recent studies reveal that hyperuricemia induces a state of immunological memory in innate immune cells through persistent epigenetic and metabolic reprogramming of monocytes and macrophages. These alterations enhance the responsiveness of innate immune cells, leading to exaggerated inflammatory reactions upon subsequent stimulation. This review synthesizes recent studies that elucidate how metabolic shifts (e.g., increased glycolysis and fumarate accumulation) and epigenetic changes (e.g., altered histone methylation and DNA methylation) reinforce this pathogenic memory. Importantly, these mechanistic insights provide the rationale for emerging therapeutic strategies: IL-1β inhibitors aim to interrupt the central inflammatory axis; metabolic modulators (e.g., metformin, statins) seek to reverse the trained metabolic state; and epigenetic therapies [e.g., histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors] hold potential to reset dysregulated immune programming. Collectively, this review argues that multi-layered intervention, such as cytokine blockade for acute control, coupled with metabolic or epigenetic remodeling for long-term reprogramming, could yield sustained disease suppression and reduced flare frequency in gout.
DOI: https://doi.org/10.37349/emd.2025.1007103
This article belongs to the special issue Pharmacological and Non-Pharmacological Management of Gout
Amyloidosis is a rare disease, corresponding to a deposition of proteins in various tissues. Amyloid light-chain (AL) amyloidosis can involve the liver in 17% to 45% of patients. Diagnosis of liver disease is based on specific criteria, coupling alkaline phosphatases and hepatomegaly. Liver stiffness is altered in cases of heart involvement, and overall, in cases of liver involvement. Liver biopsy is generally avoided due to an important bleeding risk. Treatment is essentially based on stem cell transplantation and chemotherapy, with large progress during the last decade. Liver involvement recovery is generally diagnosed with a reduction in alkaline phosphatases and in liver size.
Amyloidosis is a rare disease, corresponding to a deposition of proteins in various tissues. Amyloid light-chain (AL) amyloidosis can involve the liver in 17% to 45% of patients. Diagnosis of liver disease is based on specific criteria, coupling alkaline phosphatases and hepatomegaly. Liver stiffness is altered in cases of heart involvement, and overall, in cases of liver involvement. Liver biopsy is generally avoided due to an important bleeding risk. Treatment is essentially based on stem cell transplantation and chemotherapy, with large progress during the last decade. Liver involvement recovery is generally diagnosed with a reduction in alkaline phosphatases and in liver size.
DOI: https://doi.org/10.37349/edd.2025.100589
Aim:
To assess the incidence and predictors of hypertensive response to exercise (HRE) of blood pressure during stress echocardiography (SE) with physical exercise in patients with known or probable coronary artery disease, and the effect of HRE on the results of the five-step SE.
Methods:
The single-center study included 193 patients who underwent ABCDE-SE. The incidence of HRE, predictors of its occurrence, and the relationship with positive results of the study protocol steps were investigated.
Results:
HRE was detected in 36.3% of patients (70 patients) and occurred more frequently during the bicycle ergometer test (p = 0.027). Patients with HRE had a significantly lower peak wall motion score index (p = 0.050) and achieved a preload ratio (p = 0.035), as well as higher left anterior descending coronary artery (LAD) blood flow velocity at rest and during exercise (p = 0.009 and p = 0.008, respectively). They also showed higher peak left ventricular (LV) contractile reserve and force (p = 0.002 and p = 0.006). Reduced contractile reserve was less common in patients with HRE (p = 0.013). Predictors related to HRE development were identified: history of LAD stenting, thickness of the LV posterior wall, LAD blood flow velocity, and normal LV force at rest (p = 0.006, p = 0.022, p = 0.004, and p = 0.003, respectively), as well as a positive step C (p = 0.005).
Conclusions:
The prevalence of HRE, its predictors, and the relationship with the ABCDE-SE results were revealed. The correlation between blood pressure response to exercise and SE steps, as well as its prognostic significance, needs further study.
Aim:
To assess the incidence and predictors of hypertensive response to exercise (HRE) of blood pressure during stress echocardiography (SE) with physical exercise in patients with known or probable coronary artery disease, and the effect of HRE on the results of the five-step SE.
Methods:
The single-center study included 193 patients who underwent ABCDE-SE. The incidence of HRE, predictors of its occurrence, and the relationship with positive results of the study protocol steps were investigated.
Results:
HRE was detected in 36.3% of patients (70 patients) and occurred more frequently during the bicycle ergometer test (p = 0.027). Patients with HRE had a significantly lower peak wall motion score index (p = 0.050) and achieved a preload ratio (p = 0.035), as well as higher left anterior descending coronary artery (LAD) blood flow velocity at rest and during exercise (p = 0.009 and p = 0.008, respectively). They also showed higher peak left ventricular (LV) contractile reserve and force (p = 0.002 and p = 0.006). Reduced contractile reserve was less common in patients with HRE (p = 0.013). Predictors related to HRE development were identified: history of LAD stenting, thickness of the LV posterior wall, LAD blood flow velocity, and normal LV force at rest (p = 0.006, p = 0.022, p = 0.004, and p = 0.003, respectively), as well as a positive step C (p = 0.005).
Conclusions:
The prevalence of HRE, its predictors, and the relationship with the ABCDE-SE results were revealed. The correlation between blood pressure response to exercise and SE steps, as well as its prognostic significance, needs further study.
DOI: https://doi.org/10.37349/ec.2025.101270
Aim:
Pain and overuse syndromes are common problems among musicians. The prevalence of musculoskeletal complaints in professional musicians ranges from 62% to 93%. Excessive muscle tension, rigidity, weakness, and stiffness in various anatomical regions such as the arm, neck, and lower back are common complaints. This study investigates the prevalence and severity of musculoskeletal symptoms, such as the amount and distribution of pain in the cranio-cervical-mandibular complex, the presence of bruxism and temporomandibular noises in conservatory clarinet students.
Methods:
A 36-item questionnaire regarding the presence of musculoskeletal symptoms was sent to all clarinet students at Italian conservatories.
Results:
From the analysis of the responses of 100 students, the occurrence of pain was not related to experience and was higher during non-musical activities (70%) than during performance (38%) (P = 0.001). Female players reported higher levels of pain using a 0–10 numeric rating scale: 4 during performance, 5 during non-musical activities, while males scored 3 in both conditions. A slight positive correlation emerged between pain and years of study (P = 0.03). The most painful regions were those of the posterior neck (29–45%) and the masseter muscle (28–31%). Temporomandibular noises were prevalent in female students (female 43%, male 22%, P = 0.005) and were often associated with bruxism (P = 0.015).
Conclusions:
Clarinet students should be informed about the symptoms they may experience, but also about the prevention of these symptoms and the techniques to improve clarinet performance.
Aim:
Pain and overuse syndromes are common problems among musicians. The prevalence of musculoskeletal complaints in professional musicians ranges from 62% to 93%. Excessive muscle tension, rigidity, weakness, and stiffness in various anatomical regions such as the arm, neck, and lower back are common complaints. This study investigates the prevalence and severity of musculoskeletal symptoms, such as the amount and distribution of pain in the cranio-cervical-mandibular complex, the presence of bruxism and temporomandibular noises in conservatory clarinet students.
Methods:
A 36-item questionnaire regarding the presence of musculoskeletal symptoms was sent to all clarinet students at Italian conservatories.
Results:
From the analysis of the responses of 100 students, the occurrence of pain was not related to experience and was higher during non-musical activities (70%) than during performance (38%) (P = 0.001). Female players reported higher levels of pain using a 0–10 numeric rating scale: 4 during performance, 5 during non-musical activities, while males scored 3 in both conditions. A slight positive correlation emerged between pain and years of study (P = 0.03). The most painful regions were those of the posterior neck (29–45%) and the masseter muscle (28–31%). Temporomandibular noises were prevalent in female students (female 43%, male 22%, P = 0.005) and were often associated with bruxism (P = 0.015).
Conclusions:
Clarinet students should be informed about the symptoms they may experience, but also about the prevention of these symptoms and the techniques to improve clarinet performance.
DOI: https://doi.org/10.37349/ent.2025.1004114
Aim:
Regulatory T (Treg) cells and interleukin-17-producing T helper (Th17) cells play a critical role in successful pregnancy. Treg and Th17 cells differentiate predominantly in the thymus. Despite steroid-induced pregnancy thymic involution, the peripheral blood Treg number increases, indicating peripheral expansion. Thymic atrophy is accompanied by a decrease in T-cell receptor diversity, but is compensated for by activation of RAG2 (recombination activating genes) in the periphery, which initiates extrathymic T-cell differentiation. In addition, naive Treg enhance their suppressive activity during pregnancy, which may play an important role in the development of maternal tolerance to fetal antigens. The changes in naive Th17 thymic output during pregnancy have not been studied. The aim of the study is to determine the percentages of peripheral blood Treg and Th17 and the expression of CD45RA, CD31, RAG2, and Tim-3 on these subsets during physiological pregnancy and in non-pregnant (NP) women.
Methods:
Peripheral blood samples (n = 80) from healthy NP and pregnant women (1st, 2nd, and 3rd trimesters) were analyzed by flow cytometry to determine Treg (CD4+CD25+FOXP3+) and Th17 (CD4+RORγt+IL-17A+), and the expression of RAG2 and Tim-3 in these subsets. Treg and Th17 then subdivided into mature naive (MN, CD45RA+CD31–), recent thymic migrants (RTE, CD45RA+CD31+), CD31– memory, and CD31+ memory cells.
Results:
An increase in the Treg percentage, a decrease in Th17, and a shift in the Treg/Th17 ratio shift towards Treg were revealed in pregnant women compared to NP. A Tim-3+ Treg increase in the 1st and 3rd trimesters and Tim-3+ Th17 in the 3rd trimester were found. There was a decrease in RTE-Treg and RTE-Th17, an increase in the MN-Treg percentage, but MN-Th17 did not change during pregnancy. The RAG2 expression was increased only in Treg.
Conclusions:
The obtained data indicate that a healthy pregnancy is characterized by significant changes in the composition of naive Th17 and Tregs in peripheral blood.
Aim:
Regulatory T (Treg) cells and interleukin-17-producing T helper (Th17) cells play a critical role in successful pregnancy. Treg and Th17 cells differentiate predominantly in the thymus. Despite steroid-induced pregnancy thymic involution, the peripheral blood Treg number increases, indicating peripheral expansion. Thymic atrophy is accompanied by a decrease in T-cell receptor diversity, but is compensated for by activation of RAG2 (recombination activating genes) in the periphery, which initiates extrathymic T-cell differentiation. In addition, naive Treg enhance their suppressive activity during pregnancy, which may play an important role in the development of maternal tolerance to fetal antigens. The changes in naive Th17 thymic output during pregnancy have not been studied. The aim of the study is to determine the percentages of peripheral blood Treg and Th17 and the expression of CD45RA, CD31, RAG2, and Tim-3 on these subsets during physiological pregnancy and in non-pregnant (NP) women.
Methods:
Peripheral blood samples (n = 80) from healthy NP and pregnant women (1st, 2nd, and 3rd trimesters) were analyzed by flow cytometry to determine Treg (CD4+CD25+FOXP3+) and Th17 (CD4+RORγt+IL-17A+), and the expression of RAG2 and Tim-3 in these subsets. Treg and Th17 then subdivided into mature naive (MN, CD45RA+CD31–), recent thymic migrants (RTE, CD45RA+CD31+), CD31– memory, and CD31+ memory cells.
Results:
An increase in the Treg percentage, a decrease in Th17, and a shift in the Treg/Th17 ratio shift towards Treg were revealed in pregnant women compared to NP. A Tim-3+ Treg increase in the 1st and 3rd trimesters and Tim-3+ Th17 in the 3rd trimester were found. There was a decrease in RTE-Treg and RTE-Th17, an increase in the MN-Treg percentage, but MN-Th17 did not change during pregnancy. The RAG2 expression was increased only in Treg.
Conclusions:
The obtained data indicate that a healthy pregnancy is characterized by significant changes in the composition of naive Th17 and Tregs in peripheral blood.
DOI: https://doi.org/10.37349/ei.2025.1003214
Mpox, caused by the monkeypox virus (MPXV), has re-emerged as a global health concern due to recent outbreaks and the emergence of new variants. Current antiviral options are limited, prompting the search for alternative therapeutic strategies. This review explores the therapeutic potential of marine-derived bioactive compounds as antiviral agents against MPXV, focusing on their mechanisms of action and clinical relevance. Marine phytoconstituents, including mycosporine-like amino acids, carrageenan, fucoidans, and griffithsin, exhibit diverse antiviral, immunomodulatory, and anti-inflammatory properties. Understanding their role may offer innovative solutions for mpox management and address gaps in current treatment approaches. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science to identify peer-reviewed articles published between 2010 and June 2024 using keywords such as “mpox”, “monkeypox virus”, “marine-derived antivirals”, and “orthopoxvirus”. Emphasis was placed on studies from 2021–2024 to capture recent developments in mpox pathogenesis and marine-based therapeutics. Eligible sources included original research, systematic reviews, meta-analyses, and official health reports published in English. Marine-derived compounds demonstrate promising antiviral and immunomodulatory effects against MPXV in preclinical models. While further research is needed to confirm their clinical efficacy and address issues of scalability and safety, these agents represent a valuable adjunct or alternative for future mpox therapeutics.
Mpox, caused by the monkeypox virus (MPXV), has re-emerged as a global health concern due to recent outbreaks and the emergence of new variants. Current antiviral options are limited, prompting the search for alternative therapeutic strategies. This review explores the therapeutic potential of marine-derived bioactive compounds as antiviral agents against MPXV, focusing on their mechanisms of action and clinical relevance. Marine phytoconstituents, including mycosporine-like amino acids, carrageenan, fucoidans, and griffithsin, exhibit diverse antiviral, immunomodulatory, and anti-inflammatory properties. Understanding their role may offer innovative solutions for mpox management and address gaps in current treatment approaches. A comprehensive literature search was performed across PubMed, Scopus, and Web of Science to identify peer-reviewed articles published between 2010 and June 2024 using keywords such as “mpox”, “monkeypox virus”, “marine-derived antivirals”, and “orthopoxvirus”. Emphasis was placed on studies from 2021–2024 to capture recent developments in mpox pathogenesis and marine-based therapeutics. Eligible sources included original research, systematic reviews, meta-analyses, and official health reports published in English. Marine-derived compounds demonstrate promising antiviral and immunomodulatory effects against MPXV in preclinical models. While further research is needed to confirm their clinical efficacy and address issues of scalability and safety, these agents represent a valuable adjunct or alternative for future mpox therapeutics.
DOI: https://doi.org/10.37349/ei.2025.1003213
Aim:
Fruits from the tropical Annona genus of family Annonaceae have long been cultivated in tropical Latin America, Africa, and southeastern Asia. Asimina triloba is a temperate fruit from Annonaceae, but few comparisons between Annonaceae fruits exist. The objective was to determine how 21 days of refrigerated storage affected the carotenoids and color in ripe and overripe A. triloba. A comparison to tropical Annonaceae fruits is provided.
Methods:
Pawpaw pulp was stored refrigerated for 21 days. Total carotenoids and β-carotene were determined spectrophotometrically and by HPLC, respectively. C.I.E. L*, a*, and b* values were used to calculate hue angle, chroma, total color change (ΔE), browning index, which have been reported in A. triloba previously, and color index, whiteness index, yellowness index, the ratio of a*/b*, and percent change in L*, which are reported herein for the first time.
Results:
Overripe pulp contains 5-fold more carotenoids than ripe pulp. A significant decline in total carotenoids was observed during refrigerated storage in the overripe pulp, but not in fresh pulp. At the onset of refrigerated storage, ripe pulp was significantly less brown than overripe pulp, but became more brown during refrigerated storage. No further change in browning was observed during storage of overripe pulp.
Conclusions:
Using established conversion factors and the values generated in this study, preliminary indications are that ripe A. triloba pulp provides 4.0% (males) and 5.1% (females) of the U.S. Recommended Dietary Allowance (USRDA) of vitamin A for individuals 14 years or older, and overripe provides 3.5% and 4.6%. Carotenoids are well-characterized for Annona muricata (A. muricata), Annona reticulata (A. reticulata), and Annona squamosa (A. squamosa), but these provide less than 1% of the USRDA of vitamin A. A comparison revealed that Annonaceae fruit are nutrient-dense, provide fiber and potassium, are low in fat and protein, and have comparable calcium, iron, magnesium, potassium, and sodium levels. Understanding Annonaceae fruits nutritional value may facilitate increased economic potential.
Aim:
Fruits from the tropical Annona genus of family Annonaceae have long been cultivated in tropical Latin America, Africa, and southeastern Asia. Asimina triloba is a temperate fruit from Annonaceae, but few comparisons between Annonaceae fruits exist. The objective was to determine how 21 days of refrigerated storage affected the carotenoids and color in ripe and overripe A. triloba. A comparison to tropical Annonaceae fruits is provided.
Methods:
Pawpaw pulp was stored refrigerated for 21 days. Total carotenoids and β-carotene were determined spectrophotometrically and by HPLC, respectively. C.I.E. L*, a*, and b* values were used to calculate hue angle, chroma, total color change (ΔE), browning index, which have been reported in A. triloba previously, and color index, whiteness index, yellowness index, the ratio of a*/b*, and percent change in L*, which are reported herein for the first time.
Results:
Overripe pulp contains 5-fold more carotenoids than ripe pulp. A significant decline in total carotenoids was observed during refrigerated storage in the overripe pulp, but not in fresh pulp. At the onset of refrigerated storage, ripe pulp was significantly less brown than overripe pulp, but became more brown during refrigerated storage. No further change in browning was observed during storage of overripe pulp.
Conclusions:
Using established conversion factors and the values generated in this study, preliminary indications are that ripe A. triloba pulp provides 4.0% (males) and 5.1% (females) of the U.S. Recommended Dietary Allowance (USRDA) of vitamin A for individuals 14 years or older, and overripe provides 3.5% and 4.6%. Carotenoids are well-characterized for Annona muricata (A. muricata), Annona reticulata (A. reticulata), and Annona squamosa (A. squamosa), but these provide less than 1% of the USRDA of vitamin A. A comparison revealed that Annonaceae fruit are nutrient-dense, provide fiber and potassium, are low in fat and protein, and have comparable calcium, iron, magnesium, potassium, and sodium levels. Understanding Annonaceae fruits nutritional value may facilitate increased economic potential.
DOI: https://doi.org/10.37349/eff.2025.101098
Arterial thoracic outlet syndrome (aTOS) is a rare condition, but it has an elevated incidence among athletes due to high mechanical demands placed on the upper extremities. Post-surgical rehabilitation guidelines for aTOS are not well defined, especially in high-performance populations. Mechanically loaded neurodynamics (MLND) is a novel technique that introduces controlled external load during neurodynamic movements to optimize neurovascular adaptation and musculoskeletal function. A 47-year-old professional long-distance cyclist presented with left upper extremity pain, paresthesia, and vascular symptoms three weeks after undergoing left first rib and cervical rib resection with scalenectomy for aTOS. The patient had significant scapular dyskinesis, thoracic spine hypomobility, glenohumeral joint stiffness, and posture-related thoracic outlet compression, alongside hyperalgesia and allodynia in the ulnar nerve distribution. A structured 11-week physical therapy protocol was implemented, including traditional and MLND techniques, progressive scapular and thoracic mobility training, and sport-specific strengthening. MLND was introduced to progressively load neural tissues in median, ulnar, and radial nerve distributions while addressing musculoskeletal impairments that contribute to thoracic outlet compression. The patient demonstrated a significant reduction in pain and neurological symptoms, resolution of allodynia, restoration of full active range of motion, ≥ 93% limb symmetry index in strength testing, and an improvement in DASH score from 86.7 to 2.5. The athlete returned to unrestricted cycling at her previous level within 3.5 months post-operation. No adverse effects were reported with MLND use. This case highlights the potential role of MLND in accelerating recovery following thoracic outlet surgery in athletic populations. The approach emphasizes progressive mechanical loading to stimulate neurovascular adaptation and addresses the underlying musculoskeletal impairments contributing to neurovascular compression. Given the absence of standardized protocols for aTOS rehabilitation, MLND may serve as a safe and effective intervention. Future research should further investigate its mechanophysiological effects and clinical efficacy through controlled trials.
Arterial thoracic outlet syndrome (aTOS) is a rare condition, but it has an elevated incidence among athletes due to high mechanical demands placed on the upper extremities. Post-surgical rehabilitation guidelines for aTOS are not well defined, especially in high-performance populations. Mechanically loaded neurodynamics (MLND) is a novel technique that introduces controlled external load during neurodynamic movements to optimize neurovascular adaptation and musculoskeletal function. A 47-year-old professional long-distance cyclist presented with left upper extremity pain, paresthesia, and vascular symptoms three weeks after undergoing left first rib and cervical rib resection with scalenectomy for aTOS. The patient had significant scapular dyskinesis, thoracic spine hypomobility, glenohumeral joint stiffness, and posture-related thoracic outlet compression, alongside hyperalgesia and allodynia in the ulnar nerve distribution. A structured 11-week physical therapy protocol was implemented, including traditional and MLND techniques, progressive scapular and thoracic mobility training, and sport-specific strengthening. MLND was introduced to progressively load neural tissues in median, ulnar, and radial nerve distributions while addressing musculoskeletal impairments that contribute to thoracic outlet compression. The patient demonstrated a significant reduction in pain and neurological symptoms, resolution of allodynia, restoration of full active range of motion, ≥ 93% limb symmetry index in strength testing, and an improvement in DASH score from 86.7 to 2.5. The athlete returned to unrestricted cycling at her previous level within 3.5 months post-operation. No adverse effects were reported with MLND use. This case highlights the potential role of MLND in accelerating recovery following thoracic outlet surgery in athletic populations. The approach emphasizes progressive mechanical loading to stimulate neurovascular adaptation and addresses the underlying musculoskeletal impairments contributing to neurovascular compression. Given the absence of standardized protocols for aTOS rehabilitation, MLND may serve as a safe and effective intervention. Future research should further investigate its mechanophysiological effects and clinical efficacy through controlled trials.
DOI: https://doi.org/10.37349/emd.2025.1007102
We present the electrocardiogram (ECG) of an elderly woman with Mobitz II atrioventricular (AV) block, left bundle branch block (LBBB), and ventricular ectopic activity. At first glance, the ECG may give the misleading impression of Wenckebach periodicity and raise the suspicion of intermittent left anterior fascicular block (LAFB) and left posterior fascicular block (LPFB), suggesting an apparent alternating conduction block in the main divisions of the LBB. This intriguing appearance prompted us to present the case.
We present the electrocardiogram (ECG) of an elderly woman with Mobitz II atrioventricular (AV) block, left bundle branch block (LBBB), and ventricular ectopic activity. At first glance, the ECG may give the misleading impression of Wenckebach periodicity and raise the suspicion of intermittent left anterior fascicular block (LAFB) and left posterior fascicular block (LPFB), suggesting an apparent alternating conduction block in the main divisions of the LBB. This intriguing appearance prompted us to present the case.
DOI: https://doi.org/10.37349/ec.2025.101269
Cancer immunotherapy is one of the renowned therapeutic approaches worldwide, where its intervention has scaled further than conventional therapy. This review targets oncology researchers, immunotherapy clinicians, and public health policymakers and aims to address novel strategies for overcoming the barriers that exploit the implementation of interleukin-12 (IL-12) in cancer immunotherapy. Moreover, it emphasizes the translational challenges and clinical implications for global health interventions. IL-12 cytokine therapy is a specialized type of cancer immunotherapy that involves the systemic or local administration of IL-12 to the targeted tumor microenvironment. Over the years, IL-12 therapy has shown a promising approach in its therapeutic potential in the treatment of various cancer diseases. The molecular structure of IL-12 depicts its potential for stimulating the immune system. IL-12 enhances the production of interferon-gamma (IFN-γ), a specialized cytokine used for the potential treatment of malignant melanoma and other cancer diseases. However, despite its potent antitumor effects, IL-12 therapy has been limited by considerable toxicity observed in preclinical studies, raising concerns about its safety profile. To fully harness IL-12’s therapeutic potential, researchers should prioritize translational studies that mitigate toxicity and improve delivery mechanisms. This includes innovative approaches such as vector-based delivery systems (e.g., viral vectors and nanoparticle carriers), localized gene therapy platforms, and synergistic combination regimens that reduce systemic exposure while enhancing efficacy. Policymakers should promote flexible regulatory frameworks to accommodate adaptive clinical trial designs, while funding bodies are encouraged to support high-impact translational research that accelerates the safe clinical application of IL-12 and similar immunotherapeutic agents.
Cancer immunotherapy is one of the renowned therapeutic approaches worldwide, where its intervention has scaled further than conventional therapy. This review targets oncology researchers, immunotherapy clinicians, and public health policymakers and aims to address novel strategies for overcoming the barriers that exploit the implementation of interleukin-12 (IL-12) in cancer immunotherapy. Moreover, it emphasizes the translational challenges and clinical implications for global health interventions. IL-12 cytokine therapy is a specialized type of cancer immunotherapy that involves the systemic or local administration of IL-12 to the targeted tumor microenvironment. Over the years, IL-12 therapy has shown a promising approach in its therapeutic potential in the treatment of various cancer diseases. The molecular structure of IL-12 depicts its potential for stimulating the immune system. IL-12 enhances the production of interferon-gamma (IFN-γ), a specialized cytokine used for the potential treatment of malignant melanoma and other cancer diseases. However, despite its potent antitumor effects, IL-12 therapy has been limited by considerable toxicity observed in preclinical studies, raising concerns about its safety profile. To fully harness IL-12’s therapeutic potential, researchers should prioritize translational studies that mitigate toxicity and improve delivery mechanisms. This includes innovative approaches such as vector-based delivery systems (e.g., viral vectors and nanoparticle carriers), localized gene therapy platforms, and synergistic combination regimens that reduce systemic exposure while enhancing efficacy. Policymakers should promote flexible regulatory frameworks to accommodate adaptive clinical trial designs, while funding bodies are encouraged to support high-impact translational research that accelerates the safe clinical application of IL-12 and similar immunotherapeutic agents.
DOI: https://doi.org/10.37349/emed.2025.1001352
Hepatocellular carcinoma (HCC) ranks as the sixth most diagnosed cancer and the third most common cancer-related death globally. The underlying precise molecular mechanisms for its progression remain poorly understood. Interestingly, approximately 90% of HCC-related deaths are not due to the primary tumor itself but rather to its difficult-to-treat metastatic spread. Despite sorafenib being the first-line therapy for HCC, challenges such as drug resistance, frequent recurrence, and metastasis contribute to poor prognosis. In this context, alternative therapeutic strategies are urgently needed. A broad spectrum of phytochemicals, including polyphenolic derivatives, flavonoids, carotenoids, alkaloids, terpenes, lignans, and saponins, has shown considerable promise as potential anti-cancer agents, both in vitro and in vivo. These natural plant-derived compounds exhibit distinct and overlapping mechanisms of action, characterized by their antioxidant, anti-inflammatory, and anti-cancer properties, offering a novel approach to HCC treatment. An extensive literature search was conducted from 2010 to 2024 using reputable electronic databases such as MEDLINE, Embase, Google Scholar, Science Direct, and other reliable sources using different keywords, including HCC, medicinal plants in HCC, HCC metastasis, and mechanism of action of medicinal plants in HCC, among others. This comprehensive review aims to summarize the potential role of plant-based bioactive components in combating HCC through various cellular mechanisms, highlighting their therapeutic potential in the management of both primary and metastatic disease.
Hepatocellular carcinoma (HCC) ranks as the sixth most diagnosed cancer and the third most common cancer-related death globally. The underlying precise molecular mechanisms for its progression remain poorly understood. Interestingly, approximately 90% of HCC-related deaths are not due to the primary tumor itself but rather to its difficult-to-treat metastatic spread. Despite sorafenib being the first-line therapy for HCC, challenges such as drug resistance, frequent recurrence, and metastasis contribute to poor prognosis. In this context, alternative therapeutic strategies are urgently needed. A broad spectrum of phytochemicals, including polyphenolic derivatives, flavonoids, carotenoids, alkaloids, terpenes, lignans, and saponins, has shown considerable promise as potential anti-cancer agents, both in vitro and in vivo. These natural plant-derived compounds exhibit distinct and overlapping mechanisms of action, characterized by their antioxidant, anti-inflammatory, and anti-cancer properties, offering a novel approach to HCC treatment. An extensive literature search was conducted from 2010 to 2024 using reputable electronic databases such as MEDLINE, Embase, Google Scholar, Science Direct, and other reliable sources using different keywords, including HCC, medicinal plants in HCC, HCC metastasis, and mechanism of action of medicinal plants in HCC, among others. This comprehensive review aims to summarize the potential role of plant-based bioactive components in combating HCC through various cellular mechanisms, highlighting their therapeutic potential in the management of both primary and metastatic disease.
DOI: https://doi.org/10.37349/edd.2025.100588
Aim:
Moving beyond the traditional use/non-use dichotomy, this study examines how variations in older adults’ internet use relate to their multidimensional frailty status.
Methods:
Data were drawn from the Belgian Ageing Studies (BAS), a large-scale cross-sectional survey conducted in Flanders (Belgium) and included 2,312 individuals aged 60 and older. Internet use was categorized into non-users, basic users, selective users and allround users. Multidimensional frailty was assessed using the Comprehensive Frailty Assessment Instrument (CFAI), covering physical, psychological, social and environmental domains. Multinomial logistic regression and Chi-squared automatic interaction detection (CHAID) were conducted.
Results:
Regression analysis revealed that older adults with mild or high levels of physical frailty, as well as those with high levels of environmental frailty, were more likely to not use the internet. Furthermore, individuals with high physical frailty and high social frailty were more likely to be basic internet users. Social frailty was also linked to allround internet use, with those in the mild and high frailty categories being less likely to be allround users. However, CHAID analysis highlighted that sociodemographic factors—particularly low education and advanced age—are more strongly associated with low internet usage than frailty itself.
Conclusions:
Multidimensional frailty is associated with internet use, with mild and high frailty groups being less internet savvy.
Aim:
Moving beyond the traditional use/non-use dichotomy, this study examines how variations in older adults’ internet use relate to their multidimensional frailty status.
Methods:
Data were drawn from the Belgian Ageing Studies (BAS), a large-scale cross-sectional survey conducted in Flanders (Belgium) and included 2,312 individuals aged 60 and older. Internet use was categorized into non-users, basic users, selective users and allround users. Multidimensional frailty was assessed using the Comprehensive Frailty Assessment Instrument (CFAI), covering physical, psychological, social and environmental domains. Multinomial logistic regression and Chi-squared automatic interaction detection (CHAID) were conducted.
Results:
Regression analysis revealed that older adults with mild or high levels of physical frailty, as well as those with high levels of environmental frailty, were more likely to not use the internet. Furthermore, individuals with high physical frailty and high social frailty were more likely to be basic internet users. Social frailty was also linked to allround internet use, with those in the mild and high frailty categories being less likely to be allround users. However, CHAID analysis highlighted that sociodemographic factors—particularly low education and advanced age—are more strongly associated with low internet usage than frailty itself.
Conclusions:
Multidimensional frailty is associated with internet use, with mild and high frailty groups being less internet savvy.
DOI: https://doi.org/10.37349/edht.2025.101159
