Search Results (2,983)

The pathophysiological mechanism linking oxidative stress and cardiovascular disease (CVD) is not completely elucidated, especially in young individuals. This study aimed to examine redox status in an adolescent Montenegrin population in relation to cardiovascular risk score (CVRS). A cohort of 182 adolescents (76% girls) aged between 16 and 19 was examined. Total antioxidant status (TAS), superoxide dismutase (SOD), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and total oxidant status (TOS) were determined. Pro-oxy score, anti-oxy score, and oxy score were calculated as comprehensive parameters of overall redox homeostasis status. CVRS was calculated by summarizing several risk factors (i.e., sex, age, obesity, hypertension, dyslipidemia, impaired fasting glucose, and smoking). A significant positive correlation between CVRS and TOS (rho = 0.246, p = 0.001) and AOPP (rho = 0.231, p = 0.002) and MDA (rho = 0.339, p < 0.001), respectively, and a negative correlation with the TAS/TOS ratio (rho= −0.208, p = 0.005) was observed. An increase in pro-oxy scores as well as oxy scores with CVRS risk increase were observed. Anti-oxy scores did not differ between CVRS subgroups. There is a significant relationship between cardiovascular risk score and oxidative stress in the adolescent Montenegrin population. These findings support the possibility for improvement of age-specific CVD risk algorithms by adding redox homeostasis parameters in addition to conventional ones. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Background/Objectives: Primary liver cancer (PLC), encompassing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), constitutes a growing global health concern. Metabolic dysfunction-associated Steatotic Liver Disease (MASLD) and Type 2 diabetes mellitus (T2DM) represent a recurrent epidemiological overlap. Individuals with MASLD and T2DM (MASLD-T2DM) are at a higher risk of PLC. This scoping review highlights the epidemiological burden, the classic and novel pathogenetic frontiers, and the potential strategies optimizing the management of PLC in MASLD-T2DM. Methods: A systematic search of the PubMed, Medline, and SCOPUS electronic databases was conducted to identify evidence investigating the pathogenetic mechanisms linking MASLD and T2DM to hepatic carcinogenesis, highlighting the most relevant targets and the relatively emerging therapeutic strategies. The search algorithm included in sequence the filter words: “MASLD”, “liver steatosis”, “obesity”, “metabolic syndrome”, “body composition”, “insulin resistance”, “inflammation”, “oxidative stress”, “metabolic dysfunction”, “microbiota”, “glucose”, “immunometabolism”, “trained immunity”. Results: In the MASD-T2DM setting, insulin resistance (IR) and IR-induced mechanisms (including chronic inflammation, insulin/IGF-1 axis dysregulation, and autophagy), simultaneously with the alterations of gut microbiota composition and functioning, represent crucial pathogenetic factors in hepatocarcinogenesis. Besides, the glucose-related metabolic reprogramming emerged as a crucial pathogenetic moment contributing to cancer progression and immune evasion. In this scenario, lifestyle changes, simultaneously with antidiabetic drugs targeting IR-related effects and gut-liver axis, in parallel with novel approaches modulating immunometabolic pathways, represent promising strategies. Conclusions: Metabolic dysfunction, classically featuring MASLD-T2DM, constitutes a continuously expanding global issue, as well as a critical driver in PLC progression, demanding integrated and personalized interventions to reduce the future burden of disease. Full article

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article

Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a prevalent, multisystem disease affecting approximately 30% of adults worldwide. Obesity, along with dyslipidemia, type 2 diabetes mellitus, and hypertension, are closely intertwined with MASLD. In people with obesity, MASLD prevalence is estimated to be about 75%. Despite various approaches to MASLD treatment, dietary changes remain the most accessible and safe interventions in MASLD, especially in obese and overweight patients. Whey proteins are rich in bioactive compounds, essential amino acids with antioxidant properties, offering potential benefits for MASLD prevention and management. This state-of-the-art review summarizes whey protein impacts on a spectrum of MASLD-related manifestations, such as obesity, impaired glucose and lipid metabolism, hypertension, liver injury, oxidative stress, and inflammation. The results obtained in clinical environments, with a focus on meta-analysis, propose whey protein supplementation as a promising strategy aimed at managing multifaced MASLD disorders. Well-designed cohort studies are needed for validation of the efficacy and long-term safety of whey proteins in MASLD patients. Full article

Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article

Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan^® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

Background: The metabolic dysfunction-associated steatotic liver disease (MASLD) represents an escalating global health concern, with effective treatments still lacking. Given its complex pathogenesis, multi-targeted strategies are highly desirable. Methods: This study reports the isolation of four flavone C-glycosides (FCGs) from Dianthus superbus L. and explores their potential in treating MASLD. The bioactivity and underlying mechanisms of FCGs were systematically evaluated by integrating network pharmacology, molecular docking, and zebrafish model validation. Results: Network pharmacology analysis revealed that FCGs may modulate multiple MASLD-related pathways, including lipid metabolism, insulin signaling, inflammation, and apoptosis. Molecular docking further confirmed strong binding affinities between FCGs and key protein targets involved in these pathways. In the zebrafish model of MASLD induced by egg yolk powder, FCGs administration markedly attenuated obesity, hepatic lipid accumulation, and liver tissue damage. Furthermore, FCGs improved lipid metabolism and restored locomotor function. Molecular analyses confirmed that FCGs upregulated PPARγ expression to promote lipid metabolism, restored insulin signaling by enhancing INSR, PI3K, and AKT expression, and suppressed inflammation by downregulating TNF, IL-6 and NF-κB. Additionally, FCGs inhibited hepatocyte apoptosis by elevating the BCL-2/BAX ratio. Conclusions: These findings highlight the multi-pathway regulatory effects of FCGs in MASLD, underscoring its potential as a novel therapeutic candidate for further preclinical development. Full article

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

Epilepsy is a chronic neurological disease with a relatively high incidence in the pediatric population. Anti-seizure medication (ASM) may cause adverse drug reactions (ADRs), which may occur repeatedly. Objective: This study aimed to analyze the recurrence of ADRs caused by ASMs over a period of 122 months in hospitalized Mexican pediatric epilepsy patients. The patients were under monotherapy or polytherapy treatment, with valproic acid (VPA), phenytoin (PHT), and levetiracetam (LEV), among others. A total of 313 patients met the inclusion criteria: 211 experienced ADRs, whereas 102 did not. Patient sex, age, seizure type, nutritional status and related drugs were considered explanatory variables. Methods: Four statistical models were used to analyze recurrent events that were defined as “one or more ADRs occurred on a single day”, considering both the classification of ADR seriousness and the ASM causing the ADR. Results: A total of 499 recurrence events were identified. The recurrence risk was significantly greater among younger patients for both nonsevere and severe ADRs and among those with focal seizures for nonsevere ADRs. Interestingly, malnutrition was negatively associated with the risk of nonsevere ADRs, and obesity was positively associated with the risk of severe ADRs. Finally, LEV was associated with a significantly greater risk of causing nonsevere ADRs than VPA. However, LEV significantly reduced the risk of severe ADRs compared with VPA, and PHT increased the risk in comparison with VPA. In conclusion, this study offers a robust clinical tool to predict risk factors for the presence and recurrence of ASM-ADRs in pediatric patients with epilepsy. Full article

Introduction: The obesity paradox has been observed in patients with cardiovascular disease. The goal of this study was to evaluate whether obesity has a protective effect in patients presenting with cardiogenic shock. Method: Using a large Nationwide Inpatient (NIS) sample database, we evaluated mortality in patients with cardiogenic shock based on weight categories in adults. Results: A total of 843,020 patients over age 18 had a diagnosis of cardiogenic shock in the database. We found that overweight and obesity had the lowest mortality using univariate or multivariate analysis (overweight mortality of 20.66% vs. obesity mortality of 26.6% vs. 34.8% of normal weights). In contrast, cachexia was associated with the highest mortality in univariate analysis (cachexia 40.4%). Using multivariate analysis adjusting for age, baseline characteristics, and comorbidities, these relations remained unchanged (cachexia MVOR: 1.13; CI: 1.21–1.13; p < 0.001; overweight MVOR: 0.52, CI: 0.43–0.65; p < 0.001; obesity MVOR: 0.76, CI: 0.73–0.79; p < 0.001). After multivariate adjustment, morbid obesity had similar mortality to patients with normal weight (morbid obesity MVOR: 0.99 CI 0.95–01.03; p = 0.6) Conclusions: We observe a partial obesity paradox in patients with cardiogenic shock, showing that being overweight, followed by obesity, has the lowest mortality, whereas cachexia has the highest mortality despite multivariate adjustment. Full article

Green tea, derived from the unoxidized leaves of Camellia sinensis (L.) Kuntze, is one of the least processed types of tea and is rich in antioxidants and polyphenols. Among these, catechins—particularly epigallocatechin gallate (EGCG)—play a key role in regulating cell signaling pathways associated with various chronic conditions, including cardiovascular diseases, neurodegenerative disorders, metabolic diseases, and cancer. This review presents a comprehensive analysis of recent clinical studies focused on the therapeutic benefits and potential risks of interventions involving green tea extracts or EGCG. A systematic literature survey identified 17 relevant studies, classified into five key areas related to catechin interventions: toxicity and detoxification, drug pharmacokinetics, cognitive functions, anti-inflammatory and antioxidant properties, and obesity and metabolism. Findings from these clinical studies suggest that the health benefits of green tea catechins outweigh the potential risks. The review highlights the importance of subject genotyping for enzymes involved in catechin metabolism to aid in interpreting liver injury biomarkers, the necessity of assessing drug–catechin interactions in clinical contexts, and the promising effects of topical EGCG in reducing inflammation. This analysis underscores the need for further research to refine therapeutic applications while ensuring the safe and effective use of green tea catechins. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article