Search Results (5,446)

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies (“next-generation antioxidants”). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress–modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies. Full article

A subset of patients with inflammatory bowel disease (IBD) remains refractory to treatment despite multiple lines of advanced therapies. These patients are often categorized as having difficult-to-treat (DTT) IBD. We retrospectively analyzed 354 patients with IBD (including 112 with Crohn’s disease [CD] and 242 with ulcerative colitis [UC]) from a real-world cohort. Baseline demographic and disease characteristics, treatment history, and outcomes were compared between the DTT-IBD and non-DTT-IBD groups. Logistic regression analysis was performed to identify factors associated with DTT-IBD in CD and UC cohorts. Approximately 10.6% of the patients exposed to advanced therapy fulfilled the definition of DTT-IBD (CD: 9.8%, UC: 11.4%). Compared with patients with non-DTT-IBD, those with DTT-IBD exhibited a significantly higher exposure to multiple biologic classes, including antitumor necrosis factor (94.1% vs. 59.0%), anti-integrin (94.1% vs. 47.2%), anti-interleukin-12/23 (88.2% vs. 19.4%), and Janus kinase inhibitors (35.3% vs. 0.7%). The DTT-IBD group had a significantly lower clinical remission rate at the last follow-up than the non-DTT-IBD group (52.9% vs. 85.4%, p = 0.001). A longer interval from diagnosis to the initiation of advanced therapy was independently associated with DTT-IBD in CD (OR: 1.014 per month, 95% CI: 1.001–1.026, p = 0.026). No significant predictors for UC were identified. In conclusion, DTT-IBD, characterized by extensive biologic exposure and suboptimal long-term remission rates, accounts for approximately 10% of patients with IBD receiving advanced therapy. In CD, delayed initiation of advanced therapy may contribute to refractoriness. These findings emphasize the unmet need for earlier therapeutic intervention, better predictive markers of treatment response, and novel therapeutic mechanisms. Full article

Background: Protein–energy wasting (PEW) is a major predictor of morbidity and mortality in patients with chronic kidney disease (CKD), even before the initiation of dialysis. Its multifactorial pathogenesis includes reduced dietary intake, chronic inflammation, metabolic acidosis, hormonal disturbances, and dysbiosis of the gut microbiota. Early recognition and targeted management are crucial for preventing muscle loss, functional decline, and adverse outcomes. Methods: This narrative review summarises and integrates current evidence from the literature on nutritional and metabolic interventions to prevent and treat protein–energy wasting in patients with nondialysis chronic kidney disease. Relevant clinical trials, meta-analyses, and experimental studies published up to date were evaluated, focusing on dietary strategies, metabolic modulation, physical exercise, and gut microbiome-targeted therapies. Results: Adequate energy and protein intake remain the cornerstone of PEW management, based on available clinical and observational evidence. Individualised diets emphasising high-quality and plant-based proteins, oral nutritional supplements, and ketoanalogues can attenuate muscle wasting. Correction of metabolic acidosis and inflammation enhances protein anabolism and nitrogen balance. Physical exercise acts synergistically with dietary interventions to preserve muscle mass and function. Novel approaches—such as modulating the gut–kidney axis with pre-, pro-, and postbiotics or supplementing with short-chain fatty acids—show promise in improving metabolic and inflammatory profiles. Conclusions: The management of PEW in nondialysis CKD requires a personalised approach that integrates nutrition, physical activity, metabolic correction and microbiome modulation. Early, coordinated intervention may help to slow the progression of CKD and improve patient survival and quality of life. Full article

Postpericardiotomy syndrome (PPS) is the most frequent inflammatory after-effect of cardiac surgery and is characterized by high morbidity, delayed hospitalization, and increased long-term mortality rates. Although PPS is common, empirical anti-inflammatory therapy has historically been employed for its prevention, and mechanism-based approaches have not yet been standardized. In this literature review, which was conducted on the basis of randomized controlled trials, meta-analyses, cohort studies, and mechanistic research regarding pharmacologic interventions, surgical modalities, and biomarker-based preventive strategies, the deficiencies of a critical synthesis of existing preventive strategies and emerging risk stratification instruments for PPS are addressed. The review affirms that the most evidence-based pharmacologic intervention is colchicine, which demonstrates a consistent reduction in PPS incidence across a range of randomized trials. Nonsteroidal anti-inflammatory drugs show variable responses, whereas corticosteroids are no longer recommended for routine prophylaxis due to relapse. Specific anti–interleukin-1 therapies represent a promising novel approach for high-risk patients. Surgical interventions, such as pericardial closure using biomaterials and posterior pericardiotomy, are important and do not lead to increased hemodynamic complications, while postoperative effusions, atrial fibrillation, and tamponade are reduced. Less invasive methods may also be employed to mitigate inflammatory causes, particularly in valve-sparing procedures and congenital operations. Emerging biomarker data, including postoperative neutrophil-to-lymphocyte ratios, C-reactive protein levels, and pericardial fluid cytokines, enable the identification of high-risk patients and form the basis for a personalized prevention approach. In summary, pharmacologic prophylaxis, innovative surgical techniques, and biomarker-based risk stratification represent a pathway toward reducing the incidence and burden of PPS in modern cardiac surgery. Full article

Sarcopenic obesity, characterized by skeletal muscle loss concurrent with adipose tissue accumulation, has emerged as a global health threat. Exercise is established as an effective intervention; however, the molecular mechanisms underlying its protective effects remain incompletely defined. This study investigated whether exercise mitigates high-fat diet (HFD)-induced sarcopenic obesity, and whether the mechanism was related to the activation of the adenosine monophosphate-activated protein kinase (AMPK)/Acetyl-CoA carboxylase pathway (ACC) pathway and the inhibition of ferroptosis. Cell experiments demonstrated that palmitic acid induced ferroptosis in C2C12 mouse myoblasts. Animal experiments confirmed that HFD promoted skeletal muscle ferroptosis in C57BL/6 mice, evidenced by iron metabolism imbalance (solute carrier family 39 member14 upregulation, ferroportin downregulation), impaired antioxidant capacity (reduced glutathione, superoxide dismutase, glutathione peroxidase 4), and elevated lipid peroxidation (increased malondialdehyde). Meanwhile, both flat treadmill running and uphill treadmill running may reverse these changes by activating AMPK/ACC phosphorylation, reducing non-transferrin iron uptake, enhancing iron export and storage, and improving antioxidant status, jointly inhibiting ferroptosis and attenuating muscle mass loss and lipid deposition. These findings confirm that ferroptosis acts as one of the key pathogenic drivers in sarcopenic obesity and suggests that exercise may improve sarcopenic obesity by activating the AMPK/ACC pathway and inhibiting ferroptosis. This study provides novel mechanistic insights into exercise-mediated regulation of iron-lipid metabolism crosstalk and informs targeted interventions for sarcopenic obesity. Full article

Recent evidence has highlighted the pivotal roles of reactive oxygen species (ROS) and the SIRT1, AMPK, and mTOR signaling pathways in aging and longevity, making them attractive targets for studies of lifespan-extending interventions. We previously demonstrated that 1,1-diethoxyethane (1,1-DEE) could interact with mitochondrial complex I (NADH–ubiquinone oxidoreductase), leading to transient mitochondrial ROS (mtROS) production and activation of the AMPK pathway. This study further examined the effects of 1,1-DEE on longevity in model organisms. Treatment with 1,1-DEE decreased senescence in endothelial cell EA.hy926. In Caenorhabditis elegans (C. elegans), 1,1-DEE induced a hormetic response and extended the lifespan, whereas its structural isoform, 1,2-diethoxyethane (1,2-DEE), showed no such effect. In rat models, administration of 1,1-DEE markedly improved survival rate, mortality risk, restricted mean survival time (RMST), and median lifespan, associated with an accelerated body weight reduction. Additionally, 1,1-DEE could also enhance learning and memory, as assessed by the Morris water maze test in rats. These findings suggest that 1,1-DEE may serve as a novel small-molecule modulator of mitochondrial function and redox signaling, with potentials for promoting anti-aging and longevity. Full article

Pressure-controlled intermittent coronary sinus occlusion (PICSO) was initially developed to salvage ischemic myocardium. However, recent evidence suggests a more profound role: reawakening embryonic molecular pathways that facilitate myocardial regeneration. This review examines the paradigm shift in PICSO’s mechanism—from its traditional focus on infarct size reduction to its emerging role as a catalyst for myocardial repair through the reactivation of embryonic signaling. Findings suggested that myocardial decay could be ameliorated beyond salvage, revealing that PICSO enhances vascular activation in the coronary venous system, thereby influencing the fate of endothelial and myocardial cells. The theorem “embryonic recall” posits that PICSO induces molecular signals reminiscent of early cardiac development, offering a novel approach to cardiac repair in myocardial jeopardy. Noncoding RNA serves as a universal signaling event, thereby supporting the hypothesis. Yet, conflicting clinical outcomes highlight the need to redefine PICSO’s objectives, optimize device settings, and realize interventional strategies. The evolution of PICSO demands a radical shift in scientific perspective. Beyond ischemic salvage, its true potential may lie in harnessing regenerative mechanisms within the failing heart. Modern cardiology must adopt this dual role, bridging mechanical intervention with molecular rejuvenation to ensure its continued viability as a therapeutic option. PICSO, like the phoenix, may yet rise anew as a transformative force in cardiovascular medicine. Full article

SARS-CoV-2, the causative virus of the COVID-19 pandemic, is a highly transmissible, enveloped, single-stranded RNA virus that has mutated into several variants, complicating vaccine strategies and drug resistance. Novel treatment modalities targeting conserved structural vulnerable points are essential to combat these variants. The primary aim of the current study is to test the mechanical vulnerability of the SARS-CoV-2 virus envelope and spike proteins to focused, high-frequency ultrasound waves (25 MHz) in vitro. Utilizing a preliminary pretest and posttest study design, the study was conducted on a virus sample within a distilled water matrix, under controlled laboratory biosafety conditions. Since detailed imaging tools were unavailable, viral disruption was indirectly measured using real-time PCR cycle threshold (Ct) values. Ct values increased significantly after high-frequency ultrasound exposure, indicating a reduction in amplifiable viral genomic material. A paired t-test indicated a significant difference between the pretest and posttest Ct (p < 0.001), which is supported by Monte Carlo test results that revealed statistically significant shifting in viral load categories (p = 0.001, two-sided). Specifically, 85.7% of high-viral-load samples converted to low or moderate content, 46.7% of low or moderate samples were shifted to negative content. This intervention produced a large effect size (Cohen’s d = 2.422). These results indicate that ultrasound may offer a promising non-pharmacological approach to destroy or inactivate SARS-CoV-2 variants in an aqueous environment. Full article

This article examines the representation of women’s madness in the novel Misiá Señora by Albalucía Ángel to argue that the protagonist’s diagnosis of madness and subsequent institutionalization serve as a social construct, lack a scientific foundation and function as mechanisms of social discipline. I contend that the psychiatric procedures to which she is subjected operate less as therapeutic interventions than as punitive correctives aimed at regulating her defiance of patriarchal authority and her transgression of normative gendered behavior. This essay begins by reviewing scholarship on the novel that does not question the mental health diagnosis attributed to the main character. It then undertakes a close reading of the protagonist’s institutionalization to demonstrate how Ángel’s novel reveals madness as a device to neutralize women who resist socially prescribed roles. The analysis draws on feminist critiques of the “psy” disciplines—particularly those that interrogate the gendered construction of mental illness and the historical role of these disciplines in policing women’s bodies, emotions, and conduct. The conclusions highlight that, in Misiá Señora, the protagonist’s pathologization functions as a disciplinary tool that reinforces hegemonic gender norms by framing dissent as clinical deviance and justifying coercive forms of control. Full article

Unsafe behaviors at construction sites often originate from cognitive failures such as lapses in memory and attention. This study proposes a novel, hybrid framework to systematically identify and predict the key contributors of cognitive failures among construction workers. First, a detailed literature review was conducted to identify 30 candidate factors related to cognitive failures and unsafe behaviors at construction sites. Thereafter, 10 construction safety experts ranked these factors to prioritize the most influential variables. A questionnaire was then developed and field surveys were conducted across various construction sites. A total of 500 valid responses were collected from construction workers involved in residential, highway, and dam projects in Pakistan. The collected data was first analyzed using conventional statistical analysis techniques like correlation analysis followed by multiple linear and binary logistic regression to estimate factor effects on cognitive failure outcomes. Thereafter, machine-learning models (including support vector machine, random forest, and gradient boosting) were implemented to enable a more robust prediction of cognitive failures. The findings consistently identified fatigue and stress as the strongest predictors of cognitive failures. These results extend unsafe behavior frameworks by highlighting the significant factors influencing cognitive failures. Moreover, the findings also imply the importance of targeted interventions, including fatigue management, structured training, and evidence-based stress reduction, to improve safety conditions at construction sites. Full article

Insects acting as agricultural pests or disease vectors represent some of the greatest challenges to global health, food security and economics. Diverse technologies to combat insects of economic and medical importance have been and are continually being developed. These include natural and synthetic chemical insecticides and repellents, mass-trapping approaches and, more recently, an increasingly wide range of biological as well as genetic manipulations of insect vectors/pests. The increase in biological resistance and cross-resistance to many insecticides and repellents, the rapid expansion of human populations, as well as escalating climate change have extended or shifted the active periods and habitats of many insect species, creating new hurdles for attempts to defend humans from insects. At the same time, environmental, ecological and socio-political concerns continue to impact the utility of both current interventions as well as newly emerging innovative strategies. The near exponential increase in insect-based threats highlights the importance of basic and translational studies to design and develop novel technologies to combat detrimental insect populations. This review outlines the history of these challenges and describes the evolution of chemical insect control technologies, while highlighting existing and contemporary approaches to develop and deploy chemical repellents to address this threat to human health and agriculture. Full article

Background/Objectives: Prebiotics, which are non-digestible compounds that selectively modulate gut microbiota, are recognized for their potential to promote host health. Although their bifidogenic effect is well documented, a systematic synthesis of how this microbial modulation translates into clinical gastrointestinal (GI) and metabolic outcomes across diverse populations is needed. This review aims to integrate mechanistic insights with clinical evidence to elucidate the pathway from prebiotic structures to tangible health benefits. Methods: This comprehensive narrative review details the structural properties of major prebiotics (e.g., inulin, FOS, and GOS) that govern their fermentation and the production of short-chain fatty acids (SCFAs). To evaluate clinical efficacy, an analysis of 22 randomized controlled trials from the past decade was conducted, focusing on human studies that utilized ISAPP-recognized prebiotics as the sole intervention. Results: The analysis confirms that prebiotic supplementation consistently increased the abundance of beneficial bacteria (e.g., Bifidobacterium and Lactobacillus) and SCFA production. These changes are associated with significant clinical improvements, including enhanced stool frequency and consistency, strengthened intestinal barrier function, and modulated immune responses. Benefits have been documented in healthy individuals, children, the elderly, and those with conditions such as constipation, metabolic syndrome, and antibiotic-associated dysbiosis. However, significant inter-individual variability in response was evident, and the study designs showed notable heterogeneity in prebiotic type, dosage, and duration. Conclusions: Prebiotics are effective modulators of gut health, driving clinical benefits through selective microbial fermentation and SCFA production. The documented heterogeneity and variability highlight the need for future research to focus on personalized nutritional strategies. Key priorities include standardizing intervention protocols, elucidating dose–response relationships, integrating multi-omics data to link taxonomy to function, and exploring novel applications such as synbiotic formulations and gut–brain axis modulation. Full article

The global prevalence of obesity continues to rise and is a significant risk factor for the onset and progression of cardiovascular diseases. Despite the development of new pharmacological therapies, novel strategies are being explored to mitigate the impact of this disease. Intermittent fasting (IF) is a nutritional intervention that has gained popularity and shows potential as an innovative approach to weight management. This study aims to compile scientific evidence on various aspects of fasting, including its physiological effects, the molecular and thermogenic mechanisms involved, and recommendations regarding nutritional strategies during the refeeding period within the eating window. We conducted a narrative review, analyzing evidence available from PubMed/MEDLINE based on studies related to intermittent fasting, thermogenesis, and their associated outcomes. Our results demonstrate the existence of three commonly used IF protocols: alternate day fasting (ADF), periodic fasting (PF), and time-restricted eating (TRE). In addition to its effects on weight loss, IF has demonstrated notable benefits for cardiovascular health, oxidative stress, and metabolic function. Moreover, the interaction between the central nervous system and brown adipose tissue provides an alternative mechanism for the molecular regulation of thermogenesis. Nutritional patterns adopted during intermittent fasting play a crucial role in optimizing outcomes, with particular emphasis on the intake of proteins, fiber, bioactive compounds, and essential fatty acids during the feeding window. In summary, current evidence indicates that intermittent fasting provides a biologically robust framework for studying energy balance and holds promise for developing targeted nutritional interventions. Full article

In pursuit of global climate goals and sustainable development, countries have adopted a wide range of environmental policy instruments. This study examines the relationship between environmental policy stringency (EPS) and environmental outcomes, measured by carbon intensity (CI) and renewable energy intensity (REI), in 16 G20 countries from 1990 to 2020. The empirical findings reveal that more stringent environmental policy is a significant predictor of reduced CI and increased REI, although effects vary by policy type, time horizon, and country group. A novel sub-index-level analysis reveals that market-based incentive instruments, particularly trading schemes on CO₂ emissions and renewable energy, as well as technology support instruments, particularly wind and solar initiatives, exhibit the strongest and most robust effects. Emerging economies generally display greater responsiveness to policy interventions than advanced economies. By identifying which specific policy instruments are most effective across different development contexts, this study provides actionable insights for designing targeted climate policies that support both energy transition and sustainable development pathways. Full article

Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies often face limitations in efficacy and safety, necessitating the development of microbiome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes (C. acnes)-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. acnes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, and Cyclooxygenase-2 (COX2), whereas IAA demonstrated limited efficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reducing inflammatory cell infiltration, epidermal hyperplasia, and IL-1β expression. Transcriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as Cytochrome (CYP) 1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical formulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management. Full article