Previous
Metabolic diseases, including obesity, insulin resistance, and type 2 diabetes mellitus, are increasingly recognized as conditions characterized by chronic low-grade inflammation driven by dysregulated cytokine signaling. Persistent elevation of pro-inflammatory mediators disrupts insulin signaling and contributes to metabolic dysfunction. Nutritional interventions capable of restoring cytokine balance are emerging as promising adjunct strategies for metabolic disease management. Chickpea (Cicer arietinum L.), a widely consumed legume, is rich in polyphenols, saponins, dietary fiber, and bioactive peptides with potential immunometabolic benefits. This review critically summarizes the role of chickpea bioactives in modulating cytokine signaling networks, with particular emphasis on the IL-6-JAK-STAT3-SOCS3 axis and NF-κB pathway. Chickpea components exert antioxidant and anti-inflammatory effects, suppress pro-inflammatory cytokine production, and may improve insulin sensitivity. Additionally, their potential chemoprotective effects in obesity-associated metabolic disorders are discussed. Furthermore, this review highlights key gaps in mechanistic and translational research and proposes future directions for pathway-oriented investigations. Although current evidence supports the therapeutic potential of chickpea, further mechanistic and clinical validation is required.
Metabolic diseases, including obesity, insulin resistance, and type 2 diabetes mellitus, are increasingly recognized as conditions characterized by chronic low-grade inflammation driven by dysregulated cytokine signaling. Persistent elevation of pro-inflammatory mediators disrupts insulin signaling and contributes to metabolic dysfunction. Nutritional interventions capable of restoring cytokine balance are emerging as promising adjunct strategies for metabolic disease management. Chickpea (Cicer arietinum L.), a widely consumed legume, is rich in polyphenols, saponins, dietary fiber, and bioactive peptides with potential immunometabolic benefits. This review critically summarizes the role of chickpea bioactives in modulating cytokine signaling networks, with particular emphasis on the IL-6-JAK-STAT3-SOCS3 axis and NF-κB pathway. Chickpea components exert antioxidant and anti-inflammatory effects, suppress pro-inflammatory cytokine production, and may improve insulin sensitivity. Additionally, their potential chemoprotective effects in obesity-associated metabolic disorders are discussed. Furthermore, this review highlights key gaps in mechanistic and translational research and proposes future directions for pathway-oriented investigations. Although current evidence supports the therapeutic potential of chickpea, further mechanistic and clinical validation is required.
DOI: https://doi.org/10.37349/eemd.2026.101471
This article belongs to the special issue Role of Dysregulated Cytokine Signaling Pathways in Metabolic Disease
Short-chain fatty acids (SCFAs) are microbial-derived metabolites produced primarily through the fermentation of dietary fibre by the intestinal microbiota. Current evidence indicates that they play a key role in modulating nociception and pain processing across immune, metabolic, and neural pathways. The prevailing view that SCFAs suppress pain has been challenged by emerging evidence demonstrating that these same metabolites can also drive hyperalgesia. This apparent “SCFA paradox” persists because most studies have examined individual metabolites in isolation rather than considering them within their broader biological context. Here, we propose an integrative framework in which SCFAs function within a competitive receptor triad, and pain outcomes are dictated by the balance among three signalling axes: a pro-inflammatory immune axis driven by acetate acting through G protein-coupled receptor 43 (GPR43), a pro-resolutive metabolic axis mediated by butyrate via histone deacetylase (HDAC) inhibition and activation of GPR109A, and a direct neural sensing axis triggered by propionate through olfactory receptor 78 (OLFR78). Chronic pain, therefore, does not arise simply from the presence or absence of SCFAs, but from the pathological dominance of one of these axes shaped by specific dysbiosis profiles. This framework moves beyond correlation by providing a mechanistic basis for precision interventions designed to rebalance SCFA signalling, offering novel therapeutic opportunities for neuropathic and inflammatory pain conditions.
Short-chain fatty acids (SCFAs) are microbial-derived metabolites produced primarily through the fermentation of dietary fibre by the intestinal microbiota. Current evidence indicates that they play a key role in modulating nociception and pain processing across immune, metabolic, and neural pathways. The prevailing view that SCFAs suppress pain has been challenged by emerging evidence demonstrating that these same metabolites can also drive hyperalgesia. This apparent “SCFA paradox” persists because most studies have examined individual metabolites in isolation rather than considering them within their broader biological context. Here, we propose an integrative framework in which SCFAs function within a competitive receptor triad, and pain outcomes are dictated by the balance among three signalling axes: a pro-inflammatory immune axis driven by acetate acting through G protein-coupled receptor 43 (GPR43), a pro-resolutive metabolic axis mediated by butyrate via histone deacetylase (HDAC) inhibition and activation of GPR109A, and a direct neural sensing axis triggered by propionate through olfactory receptor 78 (OLFR78). Chronic pain, therefore, does not arise simply from the presence or absence of SCFAs, but from the pathological dominance of one of these axes shaped by specific dysbiosis profiles. This framework moves beyond correlation by providing a mechanistic basis for precision interventions designed to rebalance SCFA signalling, offering novel therapeutic opportunities for neuropathic and inflammatory pain conditions.
DOI: https://doi.org/10.37349/ent.2026.1004151
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide. While increasing parity has been associated with greater CVD risk in several populations, limited data exist on this association in South Asian women who experience some of the highest fertility rates globally. This narrative review synthesizes current literature examining the relationship between multiparity and CVD in South Asian women, including epidemiologic patterns, proposed biological mechanisms, and the influence of sociocultural factors. Evidence from South Asia suggests a possible association between high parity (particularly ≥ 4 or 5 births) and increased risk of hypertension, obesity, metabolic syndrome, and coronary heart disease. However, the available data are limited, largely cross-sectional, and occasionally contradictory. Some studies found no association or even protective effects at lower parity levels, suggesting a potential threshold or nonlinear effect. Biologically, proposed mechanisms include insulin resistance, endothelial dysfunction, and dysregulation of adipokines. Sociocultural factors such as male child preference, restricted contraceptive access, and limited autonomy in family planning decisions may also contribute to high parity and indirectly affect cardiovascular health. Although global research supports a positive association between multiparity and CVD, the evidence specific to South Asian populations remains inconsistent and underexplored. Further region-specific, longitudinal research is essential to clarify causality and inform culturally tailored screening and prevention strategies.
DOI: https://doi.org/10.37349/ec.2026.1012108
This article belongs to the special issue Cardiovascular Risk for Mothers and Offspring Resulting from Complicated Pregnancy
Cardiopulmonary interaction is a fundamental physiological process during spontaneous breathing, but it is profoundly altered in critically ill patients receiving mechanical ventilation (MV). Positive-pressure ventilation modifies intrathoracic, pleural, and transpulmonary pressures, with major effects on pulmonary vascular hemodynamics and right ventricular performance. Among these consequences, acute pulmonary hypertension (aPH) has emerged as a clinically relevant yet frequently underrecognized complication. This review summarizes the current evidence on cardiopulmonary interaction during spontaneous breathing and MV, with particular emphasis on the mechanisms driving aPH and right ventricular dysfunction in critically ill patients. A narrative review was performed using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. Free-text terms and controlled vocabulary related to positive-pressure ventilation, right ventricular dysfunction, pulmonary hypertension (PH), pulmonary vascular resistance (PVR), right heart catheterization, intensive care, and respiratory compliance were combined using Boolean operators. Priority was given to studies involving adult patients, including systematic reviews, observational studies, clinical trials, and relevant reference lists. During spontaneous breathing, cardiopulmonary interaction is governed by negative intrathoracic pressure, venous return (VR), transpulmonary pressure, and physiological ventilation-perfusion relationships. In contrast, MV reverses this physiological pressure profile and may reduce VR, increase right ventricular afterload, impair ventricular interdependence, and increase PVR. High tidal volumes, excessive positive end-expiratory pressure, increased plateau pressure, hypercapnia, hypoxemia, alveolar overdistension, and diffuse lung injury all contribute to aPH, potentially disrupting right ventricle-pulmonary artery coupling and promoting right ventricular dysfunction. MV profoundly reshapes cardiopulmonary physiology and may precipitate aPH and right ventricular dysfunction. Early recognition of these mechanisms and the application of protective ventilatory strategies are essential to reduce pulmonary and hemodynamic complications.
Cardiopulmonary interaction is a fundamental physiological process during spontaneous breathing, but it is profoundly altered in critically ill patients receiving mechanical ventilation (MV). Positive-pressure ventilation modifies intrathoracic, pleural, and transpulmonary pressures, with major effects on pulmonary vascular hemodynamics and right ventricular performance. Among these consequences, acute pulmonary hypertension (aPH) has emerged as a clinically relevant yet frequently underrecognized complication. This review summarizes the current evidence on cardiopulmonary interaction during spontaneous breathing and MV, with particular emphasis on the mechanisms driving aPH and right ventricular dysfunction in critically ill patients. A narrative review was performed using PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. Free-text terms and controlled vocabulary related to positive-pressure ventilation, right ventricular dysfunction, pulmonary hypertension (PH), pulmonary vascular resistance (PVR), right heart catheterization, intensive care, and respiratory compliance were combined using Boolean operators. Priority was given to studies involving adult patients, including systematic reviews, observational studies, clinical trials, and relevant reference lists. During spontaneous breathing, cardiopulmonary interaction is governed by negative intrathoracic pressure, venous return (VR), transpulmonary pressure, and physiological ventilation-perfusion relationships. In contrast, MV reverses this physiological pressure profile and may reduce VR, increase right ventricular afterload, impair ventricular interdependence, and increase PVR. High tidal volumes, excessive positive end-expiratory pressure, increased plateau pressure, hypercapnia, hypoxemia, alveolar overdistension, and diffuse lung injury all contribute to aPH, potentially disrupting right ventricle-pulmonary artery coupling and promoting right ventricular dysfunction. MV profoundly reshapes cardiopulmonary physiology and may precipitate aPH and right ventricular dysfunction. Early recognition of these mechanisms and the application of protective ventilatory strategies are essential to reduce pulmonary and hemodynamic complications.
DOI: https://doi.org/10.37349/ec.2026.1012109
Explanations and treatment of fibromyalgia syndrome (FMS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are controversial, and outcomes are poor. This paper describes sensation-suppression theory, a theory modelled on self-organizing control systems that are capable of adaptation in response to inputs and used in applications of artificial intelligence. The theory shows how the need to suppress inflammatory and other causes of pain or fatigue due to challenging circumstances sensitizes the neurological processing of pain and fatigue, thereby creating the amplified sensations and abnormal cognitions of central sensitivity syndromes. These syndromes are caused by errors in an evolutionarily early behavior-control mechanism of animals that comes into conflict with the later cognitive behavior-control mechanism of humans. Unlike the cognitive and current biological theories, the sensation-suppression theory explains both the personality and biological risk factors for central sensitivity syndromes and why onset is sometimes gradual and sometimes sudden. A specific form of autonomic dysregulation that could act as a new empirical test of the theory is suggested. Recovery is achieved by reversing the biological homeostatic dysregulation through a specific form of pacing where the person changes from one short, non-stressful activity to another, and where activity is calibrated to the level of illness and the patient’s current biological state. Recovery is hampered or prevented by systemic inflammation and lifestyle obligations. The theory provides a sympathetic narrative for the cause and treatment of FMS and ME/CFS and promotes a recovery lifestyle that prioritizes the needs of the patient. Prevention requires hearing what the body is saying.
Explanations and treatment of fibromyalgia syndrome (FMS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are controversial, and outcomes are poor. This paper describes sensation-suppression theory, a theory modelled on self-organizing control systems that are capable of adaptation in response to inputs and used in applications of artificial intelligence. The theory shows how the need to suppress inflammatory and other causes of pain or fatigue due to challenging circumstances sensitizes the neurological processing of pain and fatigue, thereby creating the amplified sensations and abnormal cognitions of central sensitivity syndromes. These syndromes are caused by errors in an evolutionarily early behavior-control mechanism of animals that comes into conflict with the later cognitive behavior-control mechanism of humans. Unlike the cognitive and current biological theories, the sensation-suppression theory explains both the personality and biological risk factors for central sensitivity syndromes and why onset is sometimes gradual and sometimes sudden. A specific form of autonomic dysregulation that could act as a new empirical test of the theory is suggested. Recovery is achieved by reversing the biological homeostatic dysregulation through a specific form of pacing where the person changes from one short, non-stressful activity to another, and where activity is calibrated to the level of illness and the patient’s current biological state. Recovery is hampered or prevented by systemic inflammation and lifestyle obligations. The theory provides a sympathetic narrative for the cause and treatment of FMS and ME/CFS and promotes a recovery lifestyle that prioritizes the needs of the patient. Prevention requires hearing what the body is saying.
DOI: https://doi.org/10.37349/ent.2026.1004152
Aim:
Adherence to antihypertensive medication is essential for positive outcomes among patients diagnosed with hypertension. Yet, up to 72% of individuals prescribed antihypertensives do not take medication as prescribed. Understanding mechanisms of behavior change (MoBCs) for antihypertensive adherence provides essential insight for how to change adherence behavior. This study examined the association between 4 potential MoBCs and self-reported antihypertensive adherence.
Methods:
This exploratory, cross-sectional study recruited 101 patients prescribed antihypertensive medications to complete self-report questionnaires on adherence and potential mechanisms of nonadherence. Antihypertensive adherence was assessed using the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HB-HBP). The 4 putative MoBCs for nonadherence included self-efficacy, self-regulation, behavioral automaticity, and hypertension knowledge. Associations between self-reported antihypertensive adherence and MoBCs were examined using independent samples t-tests and multivariate median regression with covariate adjustment for participant characteristics.
Results:
The sample had a mean age of 61.7 years (SD = 13.1 years), was 59.4% female (n = 60), 66.3% White (n = 67), and 7.9% Hispanic (n = 8). Low adherence was reported by 16.8% of the study sample. Participants who reported low adherence to antihypertensive medications had lower scores on the self-efficacy questionnaire (p < 0.001) and hypertension knowledge (p = 0.045). Self-efficacy and hypertension knowledge remained significantly associated with self-reported adherence in multivariate regression with covariate adjustment.
Conclusions:
The current study supports the hypothesis that self-efficacy for adherence and additionally hypertension knowledge are the MoBCs most strongly associated with self-reported adherence behavior. Behavioral interventions to improve medication adherence should consider focusing on self-efficacy and hypertension knowledge as potentially important target MoBCs. The authors recommend that future research should consider tailored intervention approaches that target specific mechanisms of adherence and specific self-reported reasons for nonadherence.
Aim:
Adherence to antihypertensive medication is essential for positive outcomes among patients diagnosed with hypertension. Yet, up to 72% of individuals prescribed antihypertensives do not take medication as prescribed. Understanding mechanisms of behavior change (MoBCs) for antihypertensive adherence provides essential insight for how to change adherence behavior. This study examined the association between 4 potential MoBCs and self-reported antihypertensive adherence.
Methods:
This exploratory, cross-sectional study recruited 101 patients prescribed antihypertensive medications to complete self-report questionnaires on adherence and potential mechanisms of nonadherence. Antihypertensive adherence was assessed using the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HB-HBP). The 4 putative MoBCs for nonadherence included self-efficacy, self-regulation, behavioral automaticity, and hypertension knowledge. Associations between self-reported antihypertensive adherence and MoBCs were examined using independent samples t-tests and multivariate median regression with covariate adjustment for participant characteristics.
Results:
The sample had a mean age of 61.7 years (SD = 13.1 years), was 59.4% female (n = 60), 66.3% White (n = 67), and 7.9% Hispanic (n = 8). Low adherence was reported by 16.8% of the study sample. Participants who reported low adherence to antihypertensive medications had lower scores on the self-efficacy questionnaire (p < 0.001) and hypertension knowledge (p = 0.045). Self-efficacy and hypertension knowledge remained significantly associated with self-reported adherence in multivariate regression with covariate adjustment.
Conclusions:
The current study supports the hypothesis that self-efficacy for adherence and additionally hypertension knowledge are the MoBCs most strongly associated with self-reported adherence behavior. Behavioral interventions to improve medication adherence should consider focusing on self-efficacy and hypertension knowledge as potentially important target MoBCs. The authors recommend that future research should consider tailored intervention approaches that target specific mechanisms of adherence and specific self-reported reasons for nonadherence.
DOI: https://doi.org/10.37349/emed.2026.1001402
This article belongs to the special issue Drug Adherence in Hypertension
The search for inexpensive raw materials for chitin production has led to the exploration of various natural resources, including some less conventional ones, such as plants and waste from the processing of various animals. In this context, the production of chitin from chicken bones and feet has been reported, attracting attention as a cheap and widely available source in some regions. However, to the best of our knowledge, birds do not possess genes that encode chitin synthases, the enzymes responsible for chitin biosynthesis. Therefore, this study analyzes the results reported in related articles, especially their FTIR spectra, to assess when the obtained material can be identified as chitin. The analysis revealed that, in some cases, there is poor agreement between the signals in these spectra and the characteristic signals established for well-characterized chitins, while in others, the spectra exhibit signals with a high noise-to-signal ratio that limits their use for identification. Furthermore, the X-ray diffraction studies reported in some of these works provide scarce support to confirm the presence of chitin in these materials. A search of two specialized databases confirmed that, to date, no results have been reported for genes expressing chitin synthases in birds. Finally, some recommendations are offered for properly addressing the studies necessary for the unambiguous identification of these materials.
The search for inexpensive raw materials for chitin production has led to the exploration of various natural resources, including some less conventional ones, such as plants and waste from the processing of various animals. In this context, the production of chitin from chicken bones and feet has been reported, attracting attention as a cheap and widely available source in some regions. However, to the best of our knowledge, birds do not possess genes that encode chitin synthases, the enzymes responsible for chitin biosynthesis. Therefore, this study analyzes the results reported in related articles, especially their FTIR spectra, to assess when the obtained material can be identified as chitin. The analysis revealed that, in some cases, there is poor agreement between the signals in these spectra and the characteristic signals established for well-characterized chitins, while in others, the spectra exhibit signals with a high noise-to-signal ratio that limits their use for identification. Furthermore, the X-ray diffraction studies reported in some of these works provide scarce support to confirm the presence of chitin in these materials. A search of two specialized databases confirmed that, to date, no results have been reported for genes expressing chitin synthases in birds. Finally, some recommendations are offered for properly addressing the studies necessary for the unambiguous identification of these materials.
DOI: https://doi.org/10.37349/ebmx.2026.101365
Aim:
This study aimed to evaluate the physicochemical, functional, and microbiological quality of Tahlaout, a traditional date-based product from the Draa-Tafilalet region of Morocco. The main objective is to compare these characteristics with international standards, including Gulf date syrup (dibs) and Egyptian date honey, to assess their potential for market valorization and formal recognition.
Methods:
A cross-sectional analytical and comparative study was conducted on thirteen Tahlaout samples collected from different women-led cooperatives. Physicochemical parameters, including pH, degree Brix (°Bx), water activity, dry matter (DM), ash content, reducing sugars, viscosity, and color, were determined using standardized methods. Functional and nutritional properties were assessed by quantifying total polyphenols, flavonoids, antioxidant activity, and mineral composition. Microbiological quality was evaluated by enumerating aerobic mesophilic flora, yeasts, molds, and total coliforms.
Results:
The majority of Tahlaout samples complied with international quality standards and exhibited high levels of bioactive and nutritional compounds: mean total polyphenol content (TPC) of 26.68 mg GAE/gS (range: 14.16–33.88), mean total flavonoid content (TFC) of 14.46 mg RE/gS (range: 5.93–23.19), mean ferric reducing antioxidant power (FRAP) of 7.80 mmol Fe2+/gS (range: 3.52–11.50), and mean DPPH inhibition of 56.93% (range: 50.81–79.32). Mineral analysis yielded a mean iron content of 5.20 mg/100 g DM (4.27–6.58), zinc of 0.43 mg/100 g DM (range: 0.25–1.45), copper of 0.96 mg/100 g DM (range: 0.77–1.35), and manganese of 1.9 mg/100 g DM (range: 1.34–2.49). Microbiological analyses indicated generally satisfactory quality. However, elevated coliform and yeast counts were detected in certain samples, suggesting possible contamination during or after processing.
Conclusions:
Tahlaout demonstrates strong potential as a high-quality traditional date-based product. Nevertheless, improvements in hygiene practices and the implementation of standardized certification protocols are necessary to ensure product safety and consistency. These findings support the formalization and sustainable development of the Tahlaout sector and contribute to the valorization of the date industry in Moroccan oasis regions.
Aim:
This study aimed to evaluate the physicochemical, functional, and microbiological quality of Tahlaout, a traditional date-based product from the Draa-Tafilalet region of Morocco. The main objective is to compare these characteristics with international standards, including Gulf date syrup (dibs) and Egyptian date honey, to assess their potential for market valorization and formal recognition.
Methods:
A cross-sectional analytical and comparative study was conducted on thirteen Tahlaout samples collected from different women-led cooperatives. Physicochemical parameters, including pH, degree Brix (°Bx), water activity, dry matter (DM), ash content, reducing sugars, viscosity, and color, were determined using standardized methods. Functional and nutritional properties were assessed by quantifying total polyphenols, flavonoids, antioxidant activity, and mineral composition. Microbiological quality was evaluated by enumerating aerobic mesophilic flora, yeasts, molds, and total coliforms.
Results:
The majority of Tahlaout samples complied with international quality standards and exhibited high levels of bioactive and nutritional compounds: mean total polyphenol content (TPC) of 26.68 mg GAE/gS (range: 14.16–33.88), mean total flavonoid content (TFC) of 14.46 mg RE/gS (range: 5.93–23.19), mean ferric reducing antioxidant power (FRAP) of 7.80 mmol Fe2+/gS (range: 3.52–11.50), and mean DPPH inhibition of 56.93% (range: 50.81–79.32). Mineral analysis yielded a mean iron content of 5.20 mg/100 g DM (4.27–6.58), zinc of 0.43 mg/100 g DM (range: 0.25–1.45), copper of 0.96 mg/100 g DM (range: 0.77–1.35), and manganese of 1.9 mg/100 g DM (range: 1.34–2.49). Microbiological analyses indicated generally satisfactory quality. However, elevated coliform and yeast counts were detected in certain samples, suggesting possible contamination during or after processing.
Conclusions:
Tahlaout demonstrates strong potential as a high-quality traditional date-based product. Nevertheless, improvements in hygiene practices and the implementation of standardized certification protocols are necessary to ensure product safety and consistency. These findings support the formalization and sustainable development of the Tahlaout sector and contribute to the valorization of the date industry in Moroccan oasis regions.
DOI: https://doi.org/10.37349/eff.2026.1010143
Food allergies are a significant global public health concern, affecting an estimated 3–8% of the population in Western nations. Although the structural and immunological basis of food allergens is increasingly well understood, the mechanisms by which processing modifies their allergenicity remain largely unresolved. This narrative review synthesizes current evidence on the effects of thermal and nonthermal processing treatments, such as high hydrostatic pressure, enzymatic hydrolysis, digestion, and chemical modification, on the structure and immunoglobulin E (IgE)-binding ability of food allergens. Fish allergens, primarily parvalbumin, were used as the primary case study throughout, given their high thermal stability, cross-reactivity, and the availability of molecular dynamics (MD) data. The review also examines how MD simulations have contributed to understanding these processing effects at the atomic scale, including conformational changes, epitope exposure, and digestibility under thermal stress. The synthesized evidence shows that, while processing can reduce allergenicity by disturbing epitopes or improving digestibility, it can also have the opposite effect by unmasking hidden epitopes or generating new ones, depending on the protein identity, processing conditions, and food matrix. A major gap identified is the limited application of long-term MD simulations under relevant stress conditions, which affects the interpretative value of existing studies. Combining MD simulation results with experimental validation offers a promising path for developing processing strategies for safer food products.
Food allergies are a significant global public health concern, affecting an estimated 3–8% of the population in Western nations. Although the structural and immunological basis of food allergens is increasingly well understood, the mechanisms by which processing modifies their allergenicity remain largely unresolved. This narrative review synthesizes current evidence on the effects of thermal and nonthermal processing treatments, such as high hydrostatic pressure, enzymatic hydrolysis, digestion, and chemical modification, on the structure and immunoglobulin E (IgE)-binding ability of food allergens. Fish allergens, primarily parvalbumin, were used as the primary case study throughout, given their high thermal stability, cross-reactivity, and the availability of molecular dynamics (MD) data. The review also examines how MD simulations have contributed to understanding these processing effects at the atomic scale, including conformational changes, epitope exposure, and digestibility under thermal stress. The synthesized evidence shows that, while processing can reduce allergenicity by disturbing epitopes or improving digestibility, it can also have the opposite effect by unmasking hidden epitopes or generating new ones, depending on the protein identity, processing conditions, and food matrix. A major gap identified is the limited application of long-term MD simulations under relevant stress conditions, which affects the interpretative value of existing studies. Combining MD simulation results with experimental validation offers a promising path for developing processing strategies for safer food products.
DOI: https://doi.org/10.37349/eff.2026.1010144
Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy with a high propensity for extrahepatic spread, most commonly to the lungs, lymph nodes, and bones. Metastases to atypical sites like the orbital and oral cavity are uncommon and often underrecognized. We report the case of a 74-year-old male with hepatitis C-related cirrhosis who was diagnosed with HCC and initially treated with locoregional therapies. Disease progression was marked by the development of biopsy-confirmed pulmonary metastases, followed by treatment with durvalumab plus tremelimumab immunotherapy and external beam radiation. Despite therapy, further progression occurred with mediastinal lymphadenopathy. The patient subsequently developed visual disturbances, and ophthalmologic evaluation identified a solitary choroidal mass consistent with metastatic HCC. Around the same time, he presented with recurrent oral bleeding, and a biopsy of a maxillary gingival lesion confirmed metastatic HCC. This case highlights the aggressive nature of advanced HCC and its potential for unusual metastatic spread. To our knowledge, this is among the few reported cases of HCC with orbital and oral metastases. Awareness of atypical metastatic presentations and a multidisciplinary approach are essential for timely diagnosis and optimal management.
Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy with a high propensity for extrahepatic spread, most commonly to the lungs, lymph nodes, and bones. Metastases to atypical sites like the orbital and oral cavity are uncommon and often underrecognized. We report the case of a 74-year-old male with hepatitis C-related cirrhosis who was diagnosed with HCC and initially treated with locoregional therapies. Disease progression was marked by the development of biopsy-confirmed pulmonary metastases, followed by treatment with durvalumab plus tremelimumab immunotherapy and external beam radiation. Despite therapy, further progression occurred with mediastinal lymphadenopathy. The patient subsequently developed visual disturbances, and ophthalmologic evaluation identified a solitary choroidal mass consistent with metastatic HCC. Around the same time, he presented with recurrent oral bleeding, and a biopsy of a maxillary gingival lesion confirmed metastatic HCC. This case highlights the aggressive nature of advanced HCC and its potential for unusual metastatic spread. To our knowledge, this is among the few reported cases of HCC with orbital and oral metastases. Awareness of atypical metastatic presentations and a multidisciplinary approach are essential for timely diagnosis and optimal management.
DOI: https://doi.org/10.37349/emed.2026.1001401
Obesity is a major global health challenge characterized by chronic low-grade inflammation and metabolic dysfunction. Among lipid-derived mediators involved in inflammation resolution, maresin-1 (MaR1)—a specialized pro-resolving mediator derived from docosahexaenoic acid (DHA) and produced mainly by M2 macrophages—has attracted increasing attention due to its potent anti-inflammatory and metabolic regulatory properties. MaR1 promotes the resolution of inflammation by limiting neutrophil infiltration, enhancing macrophage efferocytosis, and shifting cytokine profiles toward an anti-inflammatory phenotype. In addition, it modulates metabolic pathways related to insulin sensitivity and skeletal muscle glucose uptake through signaling mechanisms involving Akt and AMP-activated protein kinase (AMPK). Reduced circulating levels of MaR1 have been consistently associated with metabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease, highlighting its potential as a biomarker of metabolic health. Exercise is a cornerstone non-pharmacological strategy for obesity management and activates molecular pathways—such as AMPK and Sirtuin 1 (SIRT1)—that overlap with those regulated by MaR1. However, human studies examining how different exercise modalities influence MaR1 production remain scarce. This perspective highlights the mechanistic links between exercise and MaR1 biology and proposes a translational research agenda to investigate how aerobic, resistance, and high-intensity interval training modulate MaR1 levels. Understanding this exercise–MaR1 axis may help establish MaR1 as a biomarker of exercise responsiveness and support the development of targeted lifestyle interventions for metabolic disease management.
Obesity is a major global health challenge characterized by chronic low-grade inflammation and metabolic dysfunction. Among lipid-derived mediators involved in inflammation resolution, maresin-1 (MaR1)—a specialized pro-resolving mediator derived from docosahexaenoic acid (DHA) and produced mainly by M2 macrophages—has attracted increasing attention due to its potent anti-inflammatory and metabolic regulatory properties. MaR1 promotes the resolution of inflammation by limiting neutrophil infiltration, enhancing macrophage efferocytosis, and shifting cytokine profiles toward an anti-inflammatory phenotype. In addition, it modulates metabolic pathways related to insulin sensitivity and skeletal muscle glucose uptake through signaling mechanisms involving Akt and AMP-activated protein kinase (AMPK). Reduced circulating levels of MaR1 have been consistently associated with metabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease, highlighting its potential as a biomarker of metabolic health. Exercise is a cornerstone non-pharmacological strategy for obesity management and activates molecular pathways—such as AMPK and Sirtuin 1 (SIRT1)—that overlap with those regulated by MaR1. However, human studies examining how different exercise modalities influence MaR1 production remain scarce. This perspective highlights the mechanistic links between exercise and MaR1 biology and proposes a translational research agenda to investigate how aerobic, resistance, and high-intensity interval training modulate MaR1 levels. Understanding this exercise–MaR1 axis may help establish MaR1 as a biomarker of exercise responsiveness and support the development of targeted lifestyle interventions for metabolic disease management.
DOI: https://doi.org/10.37349/ei.2026.1003253
This article belongs to the special issue Physical Activity and Immune System in Chronic Diseases: Mechanisms and Insights
For this review paper, data on protein misfolding and aggregation in progressive myoclonus epilepsies and some developmental encephalopathies are gathered. There is evidence that in some cases of monogenic epilepsies, misfolding of the mutated protein takes place, often leading to protein aggregation. On one hand, protein aggregation reduces the amount of protein and its activity; on the other, it exerts generic toxicity to neurons. Understanding the molecular causes due to loss of normal function and gain of toxic function of the mutated aggregate-prone proteins is important to obtain new therapies. By observing the symptomatology of progressive and developmental epileptic syndromes, one can derive some conclusions about the relevance of protein misfolding and aggregation in the picture. A plausible view seems that the most severe symptoms of dementia, behavioral and psychiatric symptoms, are linked to protein aggregation and downstream effects on cellular degradation and energy systems. Finally, I discuss the potential of targeting the proteostasis network to develop novel anti-seizure and neuroprotective therapies.
For this review paper, data on protein misfolding and aggregation in progressive myoclonus epilepsies and some developmental encephalopathies are gathered. There is evidence that in some cases of monogenic epilepsies, misfolding of the mutated protein takes place, often leading to protein aggregation. On one hand, protein aggregation reduces the amount of protein and its activity; on the other, it exerts generic toxicity to neurons. Understanding the molecular causes due to loss of normal function and gain of toxic function of the mutated aggregate-prone proteins is important to obtain new therapies. By observing the symptomatology of progressive and developmental epileptic syndromes, one can derive some conclusions about the relevance of protein misfolding and aggregation in the picture. A plausible view seems that the most severe symptoms of dementia, behavioral and psychiatric symptoms, are linked to protein aggregation and downstream effects on cellular degradation and energy systems. Finally, I discuss the potential of targeting the proteostasis network to develop novel anti-seizure and neuroprotective therapies.
DOI: https://doi.org/10.37349/en.2026.1006136
This article belongs to the special issue Advances in Epilepsy Research
The popliteus is a thin, flat, triangular muscle that originates from the lateral condyle of the femur and inserts on the posterior surface of the tibia and soleal line. Injury to the popliteus musculotendinous unit is an infrequent cause of posterolateral knee pain. This can result from a traumatic event or as a result of cumulative overload. This report describes posterior knee pain from a popliteal injury that resulted from an unusual low-velocity mechanism while performing a dance movement, which can be easily missed. Clinical and ultrasonographic features that lead to the diagnosis are described. The patient was able to return to dancing after physical rehabilitation and adjustment to dance technique. The report provides an account of popliteus injury through an unusual mechanism and treatment that can aid the clinician in the diagnosis and management of popliteus injury.
The popliteus is a thin, flat, triangular muscle that originates from the lateral condyle of the femur and inserts on the posterior surface of the tibia and soleal line. Injury to the popliteus musculotendinous unit is an infrequent cause of posterolateral knee pain. This can result from a traumatic event or as a result of cumulative overload. This report describes posterior knee pain from a popliteal injury that resulted from an unusual low-velocity mechanism while performing a dance movement, which can be easily missed. Clinical and ultrasonographic features that lead to the diagnosis are described. The patient was able to return to dancing after physical rehabilitation and adjustment to dance technique. The report provides an account of popliteus injury through an unusual mechanism and treatment that can aid the clinician in the diagnosis and management of popliteus injury.
DOI: https://doi.org/10.37349/emd.2026.1007123
Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, leading to impaired skin barrier function and severe atopic manifestations. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is a rare autosomal dominant disorder characterised by recurrent bradykinin-mediated angioedema. Their coexistence has not previously been reported, and evidence on combined biologic therapy is lacking. We report a 30-year-old woman with confirmed NS and long-standing HAE-C1-INH presenting with severe pruritus, xerosis, widespread eczema, elevated IgE, eosinophilia, and trichorrhexis invaginata. Dupilumab was initiated to target T helper (Th)2-mediated inflammation. Due to persistent angioedema attacks despite prior prophylaxis, lanadelumab was introduced. Dupilumab improved eczema severity, hyperkeratosis, and hair abnormalities over 13 months. Lanadelumab reduced angioedema attacks by 88.50%, allowing dose spacing while maintaining disease control. No adverse effects or drug interactions were observed. This is the first reported case of NS and HAE-C1-INH successfully treated with dual biologic therapy. Targeting distinct immunological pathways simultaneously may represent an effective and safe strategy for complex rare disease phenotypes.
Netherton syndrome (NS) is a rare autosomal recessive disorder caused by SPINK5 mutations, leading to impaired skin barrier function and severe atopic manifestations. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is a rare autosomal dominant disorder characterised by recurrent bradykinin-mediated angioedema. Their coexistence has not previously been reported, and evidence on combined biologic therapy is lacking. We report a 30-year-old woman with confirmed NS and long-standing HAE-C1-INH presenting with severe pruritus, xerosis, widespread eczema, elevated IgE, eosinophilia, and trichorrhexis invaginata. Dupilumab was initiated to target T helper (Th)2-mediated inflammation. Due to persistent angioedema attacks despite prior prophylaxis, lanadelumab was introduced. Dupilumab improved eczema severity, hyperkeratosis, and hair abnormalities over 13 months. Lanadelumab reduced angioedema attacks by 88.50%, allowing dose spacing while maintaining disease control. No adverse effects or drug interactions were observed. This is the first reported case of NS and HAE-C1-INH successfully treated with dual biologic therapy. Targeting distinct immunological pathways simultaneously may represent an effective and safe strategy for complex rare disease phenotypes.
DOI: https://doi.org/10.37349/eaa.2026.1009125
This letter offers a critical appraisal of Riaz et al.’s study (Explor Digit Health Technol. 2026;4:101179. DOI: 10.37349/edht.2026.101179) on psychiatrists’ knowledge, perceptions, and willingness toward digital psychiatry in Pakistan. The mixed-methods design identifies critical gaps in competencies (e.g., 68.5% telepsychiatry familiarity vs. 32.5% VR) and barriers like infrastructure deficits (44.5%). However, methodological issues per STROBE guidelines such as absent response rates, convenience sampling bias, and incomplete bias mitigation limit representativeness. An adapted Newcastle-Ottawa Scale scores it 7/10, indicating moderate bias of risk from selection and non-response. Additional concerns include under-explored cultural factors. Recommendations propose a tailored LMIC digital health adoption framework emphasizing infrastructure, training, and policy to address Pakistan’s > 75% mental health treatment gap.
This letter offers a critical appraisal of Riaz et al.’s study (Explor Digit Health Technol. 2026;4:101179. DOI: 10.37349/edht.2026.101179) on psychiatrists’ knowledge, perceptions, and willingness toward digital psychiatry in Pakistan. The mixed-methods design identifies critical gaps in competencies (e.g., 68.5% telepsychiatry familiarity vs. 32.5% VR) and barriers like infrastructure deficits (44.5%). However, methodological issues per STROBE guidelines such as absent response rates, convenience sampling bias, and incomplete bias mitigation limit representativeness. An adapted Newcastle-Ottawa Scale scores it 7/10, indicating moderate bias of risk from selection and non-response. Additional concerns include under-explored cultural factors. Recommendations propose a tailored LMIC digital health adoption framework emphasizing infrastructure, training, and policy to address Pakistan’s > 75% mental health treatment gap.
DOI: https://doi.org/10.37349/edht.2026.101193
Aim:
Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While antibody-drug conjugates (ADCs) offer targeted therapeutic options, they are often limited by toxicity, immunogenicity, complex pharmacokinetics, and high production costs. Polyclonal antibodies—capable of recognizing multiple epitopes—present a promising, yet underexplored, alternative for targeted drug delivery. The stage-specific presence of secreted, stable immunoglobulins (IGs) in CRC and their potential utility in drug conjugation strategies remain largely uncharacterized.
Methods:
This study utilized electrospray ionization nano-liquid chromatography tandem mass spectrometry (ESI-nanoLC-MS/MS) proteomic analysis on pre-treatment plasma samples across CRC stages to identify stage-specific IGs. Venn diagram comparisons refined IG candidates, while protein stability was assessed using ProtParam. Molecular docking simulations (via CB-Dock2), epitope mapping (via CABS-dock), and cell-penetrating peptide (CPP) prediction were integrated to explore epitope pairing between IGs and Kirsten rat sarcoma viral oncogene homolog (K-Ras) neoantigen, evaluating their potential for polyclonal drug conjugates (pPDCs).
Results:
A total of 325 secreted IGs were initially identified, with 46 found to be stage-specific. Protein stability analysis shortlisted 5 IGs—3 for early-stage and 2 for advanced-stage CRC. Molecular docking revealed that IG heavy variable 3-64 (IGHV3-64) exhibited high-affinity binding with Irinotecan [binding free energy (ΔG) = −10.0 kcal/mol] and showed epitope-level pairing with K-Ras at residues 2–17 and 106–114. Additional CPP motif analysis supported the potential of IGHV3-64-derived peptides for intracellular delivery, reinforcing their promise in pPDC development.
Conclusions:
IGHV3-64 emerges as a strong candidate biomarker for advanced-stage CRC, demonstrating consistent binding affinity to Irinotecan and epitope pairing with K-Ras. Its inherent CPP features further support its potential for targeted, intracellular delivery in pPDCs design. These findings highlight a novel direction in personalized cancer immunotherapy, warranting further in vitro and in vivo validation to confirm clinical utility.
Aim:
Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While antibody-drug conjugates (ADCs) offer targeted therapeutic options, they are often limited by toxicity, immunogenicity, complex pharmacokinetics, and high production costs. Polyclonal antibodies—capable of recognizing multiple epitopes—present a promising, yet underexplored, alternative for targeted drug delivery. The stage-specific presence of secreted, stable immunoglobulins (IGs) in CRC and their potential utility in drug conjugation strategies remain largely uncharacterized.
Methods:
This study utilized electrospray ionization nano-liquid chromatography tandem mass spectrometry (ESI-nanoLC-MS/MS) proteomic analysis on pre-treatment plasma samples across CRC stages to identify stage-specific IGs. Venn diagram comparisons refined IG candidates, while protein stability was assessed using ProtParam. Molecular docking simulations (via CB-Dock2), epitope mapping (via CABS-dock), and cell-penetrating peptide (CPP) prediction were integrated to explore epitope pairing between IGs and Kirsten rat sarcoma viral oncogene homolog (K-Ras) neoantigen, evaluating their potential for polyclonal drug conjugates (pPDCs).
Results:
A total of 325 secreted IGs were initially identified, with 46 found to be stage-specific. Protein stability analysis shortlisted 5 IGs—3 for early-stage and 2 for advanced-stage CRC. Molecular docking revealed that IG heavy variable 3-64 (IGHV3-64) exhibited high-affinity binding with Irinotecan [binding free energy (ΔG) = −10.0 kcal/mol] and showed epitope-level pairing with K-Ras at residues 2–17 and 106–114. Additional CPP motif analysis supported the potential of IGHV3-64-derived peptides for intracellular delivery, reinforcing their promise in pPDC development.
Conclusions:
IGHV3-64 emerges as a strong candidate biomarker for advanced-stage CRC, demonstrating consistent binding affinity to Irinotecan and epitope pairing with K-Ras. Its inherent CPP features further support its potential for targeted, intracellular delivery in pPDCs design. These findings highlight a novel direction in personalized cancer immunotherapy, warranting further in vitro and in vivo validation to confirm clinical utility.
DOI: https://doi.org/10.37349/ei.2026.1003252
Regenerative agriculture has emerged as a promising framework for improving the sustainability of food systems. Interest is also growing in its potential to enhance food nutrient density. Mechanistic links between agricultural practices, soil health, and food composition are biologically plausible and supported by emerging evidence. However, substantial variability in nutrient composition across production systems, combined with methodological limitations in current research, has hindered consistent conclusions. Concurrently, regenerative and grass-fed and finished certification programs in the United States have expanded rapidly, standardizing production practices and, in some cases, incorporating environmental indicators such as soil health and biodiversity. Yet these frameworks rely primarily on the verification of practices (obligations of means) rather than the measurement of outcomes (obligations of results), particularly at the level of food composition. Despite this, nutrition-related claims, both explicit and implicit, are increasingly associated with these systems, while routine measurement of nutrient density remains absent. This perspective examines the intersection of regenerative agriculture, nutrient density, and certification systems, highlighting a structural gap between production practices, communicated claims, and measurable outcomes, and proposes a shift toward integrating obligations of results, including standardized nutrient profiling and improved data transparency, alongside existing practice-based standards. Drawing on examples such as the Bleu-Blanc-Coeur initiative, we argue that hybrid frameworks combining practices with outcome-based verification are feasible and could strengthen the scientific basis of regenerative agriculture, support more rigorous evaluation of food quality, and improve transparency and trust within the food system.
Regenerative agriculture has emerged as a promising framework for improving the sustainability of food systems. Interest is also growing in its potential to enhance food nutrient density. Mechanistic links between agricultural practices, soil health, and food composition are biologically plausible and supported by emerging evidence. However, substantial variability in nutrient composition across production systems, combined with methodological limitations in current research, has hindered consistent conclusions. Concurrently, regenerative and grass-fed and finished certification programs in the United States have expanded rapidly, standardizing production practices and, in some cases, incorporating environmental indicators such as soil health and biodiversity. Yet these frameworks rely primarily on the verification of practices (obligations of means) rather than the measurement of outcomes (obligations of results), particularly at the level of food composition. Despite this, nutrition-related claims, both explicit and implicit, are increasingly associated with these systems, while routine measurement of nutrient density remains absent. This perspective examines the intersection of regenerative agriculture, nutrient density, and certification systems, highlighting a structural gap between production practices, communicated claims, and measurable outcomes, and proposes a shift toward integrating obligations of results, including standardized nutrient profiling and improved data transparency, alongside existing practice-based standards. Drawing on examples such as the Bleu-Blanc-Coeur initiative, we argue that hybrid frameworks combining practices with outcome-based verification are feasible and could strengthen the scientific basis of regenerative agriculture, support more rigorous evaluation of food quality, and improve transparency and trust within the food system.
DOI: https://doi.org/10.37349/eff.2026.1010142
Aim:
This study aims to evaluate how demographic and treatment variables, including age, tumor type, resectability, and metastasis, affect survival outcomes across prognostic subgroups of primary malignant cardiac tumors (PMCTs).
Methods:
PMCT cases diagnosed between 2000 and 2021 were identified from Surveillance, Epidemiology, and End Results (SEER) 18 registries. 730 patients were analyzed and categorized into prognosis groups based on 5-year survival (< 50%, 50–95%, > 95%). Demographic, histologic, and treatment varieties were examined using descriptive statistics, Kaplan-Meier estimates, and Cox proportional hazards models.
Results:
Among 730 patients, most were middle-aged (56.6%), male (52.5%), and White (60.1%). Soft tissue sarcomas predominated in the poorest-prognosis group (80.3%), while hematologic malignancies were most common in intermediate prognosis (52.0%). Younger age significantly reduced mortality risk [hazard ratio (HR) 0.49–0.52; p < 0.01]. Brain and lung metastases increased mortality (HR 2.04 and 1.89; p < 0.05). Surgical resection improved survival in sarcoma-dominant tumors, while systemic metastasis predicted poorer outcomes in hematologic malignancies. Chemotherapy improved survival in sarcomas (ρ = 0.457; p < 0.0001) but was associated with poorer outcomes in hematologic cancers (ρ = −0.337; p < 0.0001).
Conclusions:
PMCT prognosis is primarily influenced by histologic subtype and resectability. Sarcoma-dominant tumors benefit from aggressive surgical and chemotherapeutic management, conversely systemic control is key for hematologic malignancies. Younger age and absence of metastasis consistently predict better outcomes. Histology-specific and early intervention strategies are critical to improving survival in this rare malignancy.
Aim:
This study aims to evaluate how demographic and treatment variables, including age, tumor type, resectability, and metastasis, affect survival outcomes across prognostic subgroups of primary malignant cardiac tumors (PMCTs).
Methods:
PMCT cases diagnosed between 2000 and 2021 were identified from Surveillance, Epidemiology, and End Results (SEER) 18 registries. 730 patients were analyzed and categorized into prognosis groups based on 5-year survival (< 50%, 50–95%, > 95%). Demographic, histologic, and treatment varieties were examined using descriptive statistics, Kaplan-Meier estimates, and Cox proportional hazards models.
Results:
Among 730 patients, most were middle-aged (56.6%), male (52.5%), and White (60.1%). Soft tissue sarcomas predominated in the poorest-prognosis group (80.3%), while hematologic malignancies were most common in intermediate prognosis (52.0%). Younger age significantly reduced mortality risk [hazard ratio (HR) 0.49–0.52; p < 0.01]. Brain and lung metastases increased mortality (HR 2.04 and 1.89; p < 0.05). Surgical resection improved survival in sarcoma-dominant tumors, while systemic metastasis predicted poorer outcomes in hematologic malignancies. Chemotherapy improved survival in sarcomas (ρ = 0.457; p < 0.0001) but was associated with poorer outcomes in hematologic cancers (ρ = −0.337; p < 0.0001).
Conclusions:
PMCT prognosis is primarily influenced by histologic subtype and resectability. Sarcoma-dominant tumors benefit from aggressive surgical and chemotherapeutic management, conversely systemic control is key for hematologic malignancies. Younger age and absence of metastasis consistently predict better outcomes. Histology-specific and early intervention strategies are critical to improving survival in this rare malignancy.
DOI: https://doi.org/10.37349/ec.2026.1012107
Obesity, diabetes mellitus (DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular diseases (CVDs) share pathogenic mechanisms like oxidative stress and inflammation. Resveratrol (RSV) offers therapeutic potential by activating the sirtuin (SIRT) signaling network. This review synthesizes RSV’s pharmacological impacts on adipose, pancreatic, hepatic, and cardiovascular tissues, focusing on the AMPK/SIRT1/PGC-1α axis, PI3K/AKT pathways, and epigenetic modulations. Despite robust preclinical data, a significant translational gap exists. Clinical evidence is heterogeneous, often contradicting animal studies due to varying dosages, durations, and population characteristics. RSV acts as a pan-SIRT activator, though its precise SIRT1 activation mechanism, direct or via NAD+ modulation, remains debated. In obesity, RSV promotes adipose beiging and thermogenesis, yet clinical weight loss is modest. For DM, it preserves β-cell function and improves insulin sensitivity, primarily benefiting diabetic populations with variable glycemic outcomes. In MASLD, RSV ameliorates steatosis and fibrosis in models, but large-scale human trials confirming histological benefits are lacking. Regarding CVDs, RSV protects against endothelial dysfunction and inflammation, showing minor improvements in biomarkers like blood pressure, though hard endpoints need validation. Major limitations hinder clinical efficacy, such as poor oral bioavailability, rapid metabolism, and significant interindividual pharmacokinetic variability. The lack of standardized formulations further complicates systemic exposure. Nevertheless, the RSV-SIRT axis remains a unified metabolic and epigenetic modulator, stabilizing cellular microenvironments across organ systems. It represents a promising target for complex metabolic syndromes. Future research should prioritize overcoming bioavailability challenges through novel delivery systems and investigating synergistic combinatorial therapies to bridge the gap between preclinical promise and clinical reality.
Obesity, diabetes mellitus (DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular diseases (CVDs) share pathogenic mechanisms like oxidative stress and inflammation. Resveratrol (RSV) offers therapeutic potential by activating the sirtuin (SIRT) signaling network. This review synthesizes RSV’s pharmacological impacts on adipose, pancreatic, hepatic, and cardiovascular tissues, focusing on the AMPK/SIRT1/PGC-1α axis, PI3K/AKT pathways, and epigenetic modulations. Despite robust preclinical data, a significant translational gap exists. Clinical evidence is heterogeneous, often contradicting animal studies due to varying dosages, durations, and population characteristics. RSV acts as a pan-SIRT activator, though its precise SIRT1 activation mechanism, direct or via NAD+ modulation, remains debated. In obesity, RSV promotes adipose beiging and thermogenesis, yet clinical weight loss is modest. For DM, it preserves β-cell function and improves insulin sensitivity, primarily benefiting diabetic populations with variable glycemic outcomes. In MASLD, RSV ameliorates steatosis and fibrosis in models, but large-scale human trials confirming histological benefits are lacking. Regarding CVDs, RSV protects against endothelial dysfunction and inflammation, showing minor improvements in biomarkers like blood pressure, though hard endpoints need validation. Major limitations hinder clinical efficacy, such as poor oral bioavailability, rapid metabolism, and significant interindividual pharmacokinetic variability. The lack of standardized formulations further complicates systemic exposure. Nevertheless, the RSV-SIRT axis remains a unified metabolic and epigenetic modulator, stabilizing cellular microenvironments across organ systems. It represents a promising target for complex metabolic syndromes. Future research should prioritize overcoming bioavailability challenges through novel delivery systems and investigating synergistic combinatorial therapies to bridge the gap between preclinical promise and clinical reality.
DOI: https://doi.org/10.37349/eemd.2026.101470
Aim:
The aim of this study was to compare the effects of high-intensity interval training (HIIT) and concurrent training (CONC) on body composition and metabolic profile in postmenopausal women.
Methods:
Forty-five postmenopausal women with overweight or obesity (50–65 years) were randomly assigned to one of three groups: HIIT group, CONC group, or control group (CG). All groups underwent a 12-week intervention, consisting of three training sessions per week, scheduled on alternate days. All dependent variables (body composition, lipid, or glycemic markers) were assessed before and after a 12-week intervention period.
Results:
The CONC and HIIT groups showed anthropometric improvements compared to the CG. In this regard, CONC and HIIT significantly (P < 0.05) reduced their body weight and body mass index (BMI) compared with the CG. This reduction was due to a decrease in fat mass, mainly in the abdominal area, as reflected by the reduction in the waist-to-hip ratio. Participants in the CONC group showed greater reductions in body weight, BMI, and body fat percentage compared with the HIIT group, while both exercise interventions produced similar improvements in metabolic biomarkers. Regarding circulating parameters, CONC and HIIT significantly (P < 0.05) reduced circulating triglycerides, total cholesterol, and LDL-cholesterol, which resulted in a decrease in the atherogenic index of plasma (AIP, calculated as log[TG/HDL-C]) compared with CG. Blood glucose and insulin levels also decreased significantly (P < 0.05) in CONC and HIIT compared with CG, with a consequent reduction in the homeostatic model assessment-insulin resistance (HOMA-IR).
Conclusions:
A 12-week program of HIIT or CONC training represents an effective strategy for improving body fat reduction and metabolic profile in sedentary postmenopausal women with overweight or obesity [ClinicalTrials.gov, identifier (ID NCT07302191)].
Aim:
The aim of this study was to compare the effects of high-intensity interval training (HIIT) and concurrent training (CONC) on body composition and metabolic profile in postmenopausal women.
Methods:
Forty-five postmenopausal women with overweight or obesity (50–65 years) were randomly assigned to one of three groups: HIIT group, CONC group, or control group (CG). All groups underwent a 12-week intervention, consisting of three training sessions per week, scheduled on alternate days. All dependent variables (body composition, lipid, or glycemic markers) were assessed before and after a 12-week intervention period.
Results:
The CONC and HIIT groups showed anthropometric improvements compared to the CG. In this regard, CONC and HIIT significantly (P < 0.05) reduced their body weight and body mass index (BMI) compared with the CG. This reduction was due to a decrease in fat mass, mainly in the abdominal area, as reflected by the reduction in the waist-to-hip ratio. Participants in the CONC group showed greater reductions in body weight, BMI, and body fat percentage compared with the HIIT group, while both exercise interventions produced similar improvements in metabolic biomarkers. Regarding circulating parameters, CONC and HIIT significantly (P < 0.05) reduced circulating triglycerides, total cholesterol, and LDL-cholesterol, which resulted in a decrease in the atherogenic index of plasma (AIP, calculated as log[TG/HDL-C]) compared with CG. Blood glucose and insulin levels also decreased significantly (P < 0.05) in CONC and HIIT compared with CG, with a consequent reduction in the homeostatic model assessment-insulin resistance (HOMA-IR).
Conclusions:
A 12-week program of HIIT or CONC training represents an effective strategy for improving body fat reduction and metabolic profile in sedentary postmenopausal women with overweight or obesity [ClinicalTrials.gov, identifier (ID NCT07302191)].
DOI: https://doi.org/10.37349/eemd.2026.101469
This article belongs to the special issue Metabolic Syndrome in Menopause
