Search Results (968)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global public health issue, affecting approximately 25% of the population and currently offering limited treatment options. Trimetazidine (TMZ) serves as a metabolic modulator that shifts cellular energy metabolism from fatty acid oxidation to glucose oxidation, thereby providing a novel therapeutic strategy aimed at addressing the underlying metabolic dysfunctions that contribute to the pathogenesis of MASLD. Our study aims to assess the efficacy of trimetazidine in improving hepatic steatosis, inflammation, and various metabolic parameters. Methods: In this double-masked, randomized controlled trial, 60 patients with confirmed MASLD diagnoses were randomly assigned in a 1:1 ratio to receive either trimetazidine 20 mg three times daily or a placebo, alongside lifestyle modifications, for 24 weeks. The trial was conducted in accordance with the Declaration of Helsinki and approved by the ethics committees of both participating institutions. We measured changes in hepatic steatosis, non-invasive fibrosis scores, inflammatory markers (including interleukin-6, tumor necrosis factor-alpha, and highly sensitive C-reactive protein), liver enzymes, and lipid profiles at baseline and at the end of the 24 weeks. Results: Hepatic steatosis decreased significantly, with controlled attenuation parameter scores from 352.5 to 302 dB/m in the TMZ group compared to the control (p < 0.001). TNF-α was reduced significantly in the TMZ group compared to the control group (p = 0.001). Fibrosis to AST score decreased from 0.49 to 0.25 in the TMZ group (p < 0.001). Aspartate aminotransferase decreased significantly compared to the control group (p 0.032). Notably, TMZ also imparted cardioprotective benefits, reducing total cholesterol by 14%, LDL by 17% (both p < 0.05), and triglycerides by 16% (p = 0.176). Conclusions: This groundbreaking trial supports the potential of trimetazidine as a promising therapeutic agent for MASLD, indicating substantial improvements in hepatic steatosis, inflammation, and metabolic disturbances. These findings underscore the urgency and importance of further multicenter trials to validate trimetazidine’s efficacy as a disease-modifying therapy for MASLD. Full article

Hypertension in adolescence causes early vascular injury manifesting as endothelial dysfunction (ED), which signifies elevated cardiovascular risk. This review synthesizes recent insights (2020–2025) into ED’s mechanisms and detection in hypertensive youth. We highlight how reduced nitric oxide bioavailability, oxidative stress, inflammation, and hormonal changes in puberty contribute to ED and consequent vascular remodeling. Non-invasive diagnostic tools (e.g., flow-mediated dilation, peripheral arterial tonometry) reveal that even asymptomatic hypertensive adolescents have measurable ED linked to arterial stiffness and cardiac changes. Encouragingly, ED in youth appears reversible: exercise and dietary interventions improve endothelial function, and pharmacotherapy (ACE inhibitors, ARBs) can restore endothelial health beyond blood pressure control. Early identification of ED in hypertensive adolescents is therefore critical—it not only refines risk stratification (e.g., unmasking high-risk “white-coat” hypertension) but also presents an opportunity to initiate lifestyle modifications and therapy to preserve vascular function. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master transcriptional regulator of cellular antioxidant responses through orchestration of cytoprotective gene expression, establishing its significance as a therapeutic target in cerebral pathophysiology. Classical electrophilic NRF2 activators, despite potent activation potential, exhibit paradoxically reduced therapeutic efficacy relative to single antioxidants, attributable to concurrent oxidative stress generation, glutathione depletion, mitochondrial impairment, and systemic toxicity. Although emerging non-electrophilic pharmacological activators offer therapeutic potential, their utility remains limited by bioavailability and suboptimal potency, underscoring the imperative for innovative therapeutic strategies to harness this cytoprotective pathway. Non-pharmacological interventions, including neuromodulation, physical exercise, and lifestyle modifications, activate NRF2 through non-canonical, non-electrophilic pathways involving protein–protein interaction inhibition, KEAP1 degradation, post-translational and transcriptional modulation, and protein stabilization, though mechanistic characterization remains incomplete. Such interventions utilize multi-mechanistic approaches that synergistically integrate multiple non-electrophilic NRF2 pathways or judiciously combine electrophilic and non-electrophilic mechanisms while mitigating electrophile-induced toxicity. This strategy confers neuroprotective effects without the contraindications characteristic of classical electrophilic activators. This review comprehensively examines the mechanistic underpinnings of non-pharmacological NRF2 modulation, highlighting non-electrophilic activation pathways that bypass the limitations inherent to electrophilic activators. The evidence presented herein positions non-pharmacological interventions as viable therapeutic approaches for achieving non-electrophilic NRF2 activation in the treatment of cerebrovascular and neurodegenerative pathologies. Full article

Background: For the first time, humanity is facing the worldwide challenge of global population aging over 80 years. As individuals age, energy acquisition and metabolism undergo significant changes, leading to a progressive decline in energy intake, absorption, and utilization. These changes contribute to malnutrition, loss of muscle mass, frailty, hormonal decline, mineral depletion, and impaired hydration, all of which increase the risk of morbidity and decrease quality of life. In addition, as life expectancy increases, advanced age often brings a gradual loss of autonomy, mirroring early-life dependency. Objectives: Addressing this age shift requires targeted interventions to support the wellness of the growing very elderly population. This review provides an overview of healthy aging through an integrated approach that includes nutritional intervention, lifestyle modifications, and targeted supplementation to support functional independence and overall well-being in older adults. The guiding principle is that longevity matters less than aging well. Full article

For a few decades, Type 2 Diabetes (T2D) has been recognized as a worldwide public health issue. T2D relies on systemic insulin resistance leading to Beta cell dysfunction. Nowadays, lifestyle modifications, such as improving eating habits and increasing physical activity, represent the first recommendations for managing T2D. Physical exercise, as a structured physical activity, is now considered as a non-pharmacological treatment with a wide range of beneficial effects, especially for people living with T2D. The review intends to summarize the current knowledge of physical exercise benefits in a context of T2D: from “unwanted” adipose tissue reduction to Beta cell health improvement. Moreover, we try to suggest an underlying mechanism explaining physical exercise beneficial effects in the context of T2D focusing on exerkines, molecules secreted in response to physical exercise. With this review, we highlight the beneficial impact of post-exercise secretions on Beta cell health and encourage research to continue in this direction. Identifying new exerkines with beneficial effects in the context of T2D could represent a promising approach for managing metabolic diseases. Full article

Breast cancer remains a critical global health challenge, with over 2.1 million new cases annually. This review systematically evaluates recent advancements (2022–2024) in machine and deep learning approaches for breast cancer detection and risk management. Our analysis demonstrates that deep learning models achieve 90–99% accuracy across imaging modalities, with convolutional neural networks showing particular promise in mammography (99.96% accuracy) and ultrasound (100% accuracy) applications. Tabular data models using XGBoost achieve comparable performance (99.12% accuracy) for risk prediction. The study confirms that lifestyle modifications (dietary changes, BMI management, and alcohol reduction) significantly mitigate breast cancer risk. Key findings include the following: (1) hybrid models combining imaging and clinical data enhance early detection, (2) thermal imaging achieves high diagnostic accuracy (97–100% in optimized models) while offering a cost-effective, less hazardous screening option, (3) challenges persist in data variability and model interpretability. These results highlight the need for integrated diagnostic systems combining technological innovations with preventive strategies. The review underscores AI’s transformative potential in breast cancer diagnosis while emphasizing the continued importance of risk factor management. Future research should prioritize multi-modal data integration and clinically interpretable models. Full article

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article

Aims: Individual weight loss results achieved with Glucagon-like Peptide-1 receptor agonists (GLP-1RA) vary significantly. Our aim was to describe the characteristics of patients with obesity who achieved ≥ 20% total weight loss (TWL) on liraglutide and appraise those findings through the prism of an evolving spectrum of GLP-1RA. Methods: This longitudinal prospective cohort study included 21 patients (90.5% females, age 50 (IQR 17) years, class II/III obesity (Body Mass Index ≥ 35 kg/m²) followed at the Edmonton Adult Bariatric Clinic for 65.1 (IQR 15.5) weeks. All patients received treatment with liraglutide 3.0 mg subcutaneously daily along with involvement in an integrated lifestyle modification program. Results: Liraglutide was well-tolerated, with its benefits experienced by >90% of patients. The vast majority were consistently tracking calories (95.2%, n = 20) and protein intake (90.5%, n = 19), achieving a calorie deficit of 651 (IQR 323) kcal/day, and had their mental health conditions and psychological issues successfully managed. At 16, 26, and 52 weeks, TWL was 14.3% (IQR 3.7), 18.7% (IQR 8.8), and 25.9% (IQR 9.6), respectively (p < 0.001). Over 20% TWL was achieved by 72.2% of patients by week 52. Conclusions: A select number of patients with obesity will attain weight loss that rivals bariatric surgery using liraglutide monotherapy. Despite liraglutide being less effective compared to newer agents on the market, some individuals will respond strongly and should be considered when other therapies are inaccessible. Given the societal burden and numerous challenges faced by people with obesity, GLP-1RA should be pursued in clinical practice to assist in achieving weight loss goals while being convenient and safe. Full article

Objectives: Obesity has become a major health issue, with multifactorial etiologies involving lifestyle, genetic, and neuroendocrine mechanisms. Despite public health campaigns and lifestyle interventions, long-term weight loss is often difficult to achieve or sustain. This literature review aims to summarize current knowledge on the main molecular mechanisms that hinder weight loss and to summarize the newest therapeutic strategies targeting obesity. Methods: The literature review was conducted using PubMed, Scopus, and Web of Science databases, with a preference for peer-reviewed original articles, systematic reviews, and meta-analyses. Eligible studies were required to be published in the English language and within the last ten years (2015–2025), with the exception of historically significant publications. A total of 112 articles were included in our review. Results: Obesity is a complex, chronic, recurrent metabolic condition that requires personalized, multidisciplinary treatment approaches. In this review, we summarize the major molecular mechanisms underlying weight gain and weight maintenance in obesity. In this literature review, we address the metabolic memory and epigenetics that act through DNA and histone modifications and micro interfering RNAs, resulting in an energy imbalance that can be passed on to further generations. The dysfunction of adipose tissue contributes to chronic low-grade inflammation and insulin resistance, leading to more severe obesity. The ratio of white, beige, and brown adipocytes also plays an important role in regulating energy balance. Novel medical interventions offer promising results in attenuating these mechanisms against successful weight loss. Conclusions: Current interventions, including calorie restriction, physical activity, and pharmacological treatment together, may show great promise in combating obesity, but long-term efficacy and safety remain to be established. Full article

Background/Objectives: In hypertension (HTN), lifestyle modification is important for controlling blood pressure (BP) and lipidemic profile. The HINTreat trial showed that an anti-inflammatory diet was associated with improved endothelial function, after six months of intensive nutritional treatment. Methods: This post hoc analysis of the HINTreat trial examined how adherence to various nutritional patterns like the Mediterranean Diet (MedDiet), the Dietary Approaches to Stop Hypertension (DASH) diet, and anti-inflammatory diet, had impact on the blood lipids profile and the CVD risk. Patients with stage 1 HTN, allocated either on intensive lifestyle treatment (ILT) or usual care (UC) standard treatment, participated in the analysis. From the original sample size of the HINTreat trial, all patients that were prescribed lipid lowering medication at any time of the study period were excluded from the total analysis; thus, the intervention and the control groups consisted of 33 and 28 patients, respectively. Nutritional intakes were assessed with repeated 24 h recalls from the previous day, and dietary indexes and scores were calculated as follows: MedDiet score, DASH index, and Dietary Inflammatory Index (DII). After six months of intervention, changes in the nutritional indexes and their effect on the lipidemic profile and CVD risk were analyzed. Results: In the ILT group, reductions were noted in Ambulatory Blood Pressure Monitoring (ABPM) for day systolic BP (SBP) (−12.7 mmHg) and diastolic BP (DBP) (−8.4 mmHg), total cholesterol (TC) (−35.4 mg/dL), triglycerides (TG) (−21.4 mg/dL), LDL cholesterol (LDL-C) (−27.5 mg/dL) concentrations, and CVD risk score (−1.5%), p < 0.001 for all. Multiple regression analysis showed that dietary quality indices independently influenced improvements in blood lipid profile and cardiovascular disease (CVD) risk among patients receiving ILT. Specifically, a higher Mediterranean Diet (MedDiet) score was significantly associated with reductions in TC (B = −7.238, p < 0.001), TG (B = −4.103, p = 0.035), and LDL-C (B = −6.431, p = 0.004). The DASH index was positively associated with TG levels (B = 9.913, p = 0.010), suggesting a more complex relationship that may require further investigation. In addition, DII was positively associated with increased CVD risk (B = 0.973, p < 0.001). Conclusions: The findings suggest that ILT can improve BP levels, target blood lipids concentrations, and reduce CVD risk in patients with stage 1 HTN. Full article

Background and Clinical Significance: As a common inflammatory skin disorder, acne vulgaris is classically associated with sebum overproduction, follicular hyper keratinization, and Cutibacterium acnes proliferation. Emerging evidence suggests a link between severe or treatment-resistant acne and metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension. This case series aims to explore the clinical overlap between acne and metabolic dysfunction and highlight the relevance of multidisciplinary evaluation. Case Presentation: Three patients with severe acne vulgaris and coexisting metabolic abnormalities were evaluated at a dermatology clinic in Oradea, Romania, between 2023 and 2024. Each patient underwent dermatologic examination, laboratory testing for metabolic and hormonal parameters, and individualized treatment. Management strategies included topical/systemic acne therapies combined with metabolic interventions (lifestyle modifications, metformin (in two cases), and lipid-lowering agents). Case 1 (female, 23) had obesity, insulin resistance, dyslipidemia, and polycystic ovary syndrome (PCOS). Case 2 (male, 19) presented with central obesity and atherogenic dyslipidemia. Case 3 (male, 18) showed insulin resistance, overweight status, and elevated inflammatory markers. All three showed suboptimal response to standard acne treatment. Adjunct metabolic management resulted in partial improvement within 3 months. One patient required isotretinoin after metabolic stabilization. Conclusions: These cases underscore the interplay between acne and metabolic dysfunction. Insulin resistance and systemic inflammation may contribute to therapeutic resistance in acne. Early recognition of metabolic syndrome features in patients with severe acne may improve treatment outcomes. Dermatologists should consider metabolic screening to guide comprehensive, multidisciplinary care. Full article

Background/Objectives: Polycystic Ovary Syndrome (PCOS), as a multifactorial chronic disease, can cause heterogeneous metabolic, physical, and psychological disorders as well as infertility in both obese and non-obese patients. Therefore, this review aimed to present differences in pathophysiology, clinical presentation, and therapy in obese and non-obese patients with PCOS. Methods: A non-systematic review was conducted by searching papers published in English from 2010 to 2024 in MEDLINE. Results: Obesity in PCOS significantly contributes to IR and worsens metabolic dysfunction. Lifestyle modifications, including a balanced diet and regular exercise, are the first line of treatment. Pharmacological therapies, such as metformin, GLP-1 receptor agonists, myoinositol, and resveratrol, are used to improve insulin sensitivity, regulate the hormonal milieu, and reduce hyperandrogenism. Metformin is widely used to improve glucose metabolism and reduce androgen levels, while myoinositol is effective in promoting ovarian function. GLP-1 receptor agonists and resveratrol improve metabolic and reproductive outcomes. For patients with severe obesity, bariatric surgery offers substantial improvements in body composition, metabolic function, and fertility. Combination therapies, such as metformin and GLP-1 receptor agonists, provide comprehensive treatment for both reproductive and metabolic aspects of PCOS. Conclusions: The first-line treatment for PCOS is a lifestyle-modifying strategy. PCOS patients with insulin resistance and obesity would mostly benefit from combination therapy with metformin and GLP-1 receptor agonists. Full article

Background/Objectives: Anxiety and depression are common among individuals with coronary heart disease (CHD) and pose significant barriers to lifestyle modifications. Evidence on sex-related differences in anxiety and depression following cardiac rehabilitation (CR) remains inconclusive. This study aims to assesses the prevalence and changes in anxiety and depression symptoms during CR and explores potential sex differences. Methods: A quasi-experimental one-group pretest–post-test design was employed, measuring self-reported anxiety and depression symptoms utilizing the Hospital Anxiety and Depression Scale (HADS). Results: HADS was reported by 175 patients, 122 men and 53 women, at CR admission and discharge between 1 January 2022 and 30 April 2024. The prevalence of anxiety symptoms (HADS-anxiety score ≥ 8) significantly decreased from 28.2% at admission to 16.9% at discharge, while depression prevalence dropped (HADS-depression score ≥ 8) from 16.3% to 6.2%. Statistically significant sex differences were observed in depression prevalence at discharge, with women exhibiting lower symptom prevalence. Both sexes experienced significant HADS-anxiety and HADS-depression score reductions (p < 0.001) in both the overall sample and the sub-analysis of patients presenting with symptoms at admission. Women initially presented higher HADS-anxiety scores and significantly greater HADS-anxiety score reductions (p = 0.014) than men. No significant sex differences were observed in the reduction in HADS-depression scores. Conclusions: The prevalence of anxiety and depression symptoms significantly decreased among both sexes compared to admission, with women experiencing greater symptom reduction at discharge than men. Further research is needed to determine specific CR components contributing to these improvements. Full article

Background: Polycystic ovary syndrome (PCOS) is a complex and multifactorial disorder affecting reproductive, endocrine, and metabolic functions in women of reproductive age. While environmental and lifestyle factors play a role, increasing evidence highlights the contribution of genetic and epigenetic mechanisms to its pathogenesis. Objective: This narrative review aims to provide an updated overview of the current evidence regarding the role of genetic variants, gene expression patterns, and epigenetic modifications in the etiopathogenesis of PCOS, with a focus on their impact on ovarian function, fertility, and systemic alterations. Methods: A comprehensive search was conducted across MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Library using MeSH terms including “PCOS”, “Genes involved in PCOS”, and “Etiopathogenesis of PCOS” from January 2015 to June 2025. The selection process followed the SANRA quality criteria for narrative reviews. Seventeen studies published in English were included, focusing on original data regarding gene expression, polymorphisms, and epigenetic changes associated with PCOS. Results: The studies analyzed revealed a wide array of molecular alterations in PCOS, including the dysregulation of SIRT and estrogen receptor genes, altered transcriptome profiles in cumulus cells, and the involvement of long non-coding RNAs and circular RNAs in granulosa cell function and endometrial receptivity. Epigenetic mechanisms such as the DNA methylation of TGF-β1 and inflammation-related signaling pathways (e.g., TLR4/NF-κB/NLRP3) were also implicated. Some genetic variants—particularly in DENND1A, THADA, and MTNR1B—exhibit signs of positive evolutionary selection, suggesting possible ancestral adaptive roles. Conclusions: PCOS is increasingly recognized as a syndrome with a strong genetic and epigenetic background. The identification of specific molecular signatures holds promise for the development of personalized diagnostic markers and therapeutic targets. Future research should focus on large-scale genomic studies and functional validation to better understand gene–environment interactions and their influence on phenotypic variability in PCOS. Full article

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article