Search Results (28,035)

Due to the complex pathophysiology and serious outcomes of autoimmune myocarditis, we sought to determine whether ethanolic lemon balm extract (LBE) could attenuate disease progression and development of dilative cardiomyopathy (DCM). EAM was induced in Dark Agouti rats by immunization with porcine myosin. Fifty animals were allocated to five groups: healthy controls, untreated EAM, and EAM treated with LBE (50, 100, or 200 mg/kg) for six weeks. Hemodynamic parameters were monitored, and echocardiography assessed cardiac structure and function. Inflammatory, oxidative, fibrotic, and apoptotic markers were analyzed. Immunological profiling revealed that LBE significantly decreased proinflammatory cytokines (IL-1, IL-6, TNF-α, IL-4, IL-17) while restoring anti-inflammatory IL-10 levels (p < 0.05). Antioxidant activity was confirmed by reduced levels of O₂⁻, H₂O₂, and TBARS, accompanied by significant increases in SOD, CAT, and GSH activity (p < 0.05), and upregulation of SOD1 and SOD2 gene expression. Additionally, LBE (200 mg/kg) markedly reversed fibrotic remodeling through suppression of TGF-β expression and collagen deposition, as shown by Sirius Red staining, and mitigated apoptosis by modulating Bax/Bcl-2 balance and reducing TUNEL-positive cells. Collectively, these findings suggest that LBE exerts strong cardioprotective effects in EAM by regulating inflammatory, oxidative, fibrotic, and apoptotic pathways, thereby preventing myocarditis progression toward DCM. Full article

Background/Objectives: Lipid nanoparticles (LNPs) are actively being studied as therapeutics and vaccines for various diseases. While LNPs can deliver nucleic acids, their efficiency is limited by the multi-step pathways involved in intracellular trafficking. Crucially, endosomal recycling-driven exocytosis acts as a major problem, rerouting LNPs away from the cytosol and thereby preventing efficient nucleic acid release. Upon entering the cell, LNPs are frequently expelled via endosomal recycling before delivering nucleic acids to cytosol. Previous studies reported that inhibition or deletion of Exo70, a component of the exocyst complex, leads to the accumulation of endosomes because of preventing endosomal recycling. In this study, we investigate the impact of Exo70 inhibition by endosidin-2 (ES-2), an Exo70 inhibitor, on LNP delivery efficiency. Methods: SM-102, cholesterol, DMG-PEG, and DSPC were dissolved in ethanol, while mRNA was dissolved in an aqueous phase to formulate LNPs. Co-treatment of ES-2 with LNPs was performed to evaluate its effect on mRNA delivery, and the resulting delivery efficiency was assessed both in vitro and in vivo. Results: Co-treatment of ES-2 with LNPs significantly enhanced mRNA delivery efficiency, resulting in up to a 4.06-fold increase in vitro and a 3.63-fold increase in vivo. Conclusions: Our findings demonstrate that suppression of Exo70 significantly enhances the mRNA delivery efficiency of LNPs, and this strategy could be applied for the development of mRNA therapeutics. Full article

Background: Hypertension is one of the most common noncommunicable diseases. Objectives: This research assessed the magnitude of hypertension among young adults, identified its key determinants, and explored potential strategies adopted for prevention. Methods: A cross-sectional design was employed, including 1606 participants aged 18 years and older, recruited through convenience sampling from universities and community settings. Data were collected using a content-validated questionnaire covering sociodemographic information, personal and family medical history, and lifestyle habits. Results: Of the participants, 993 (61.8%) reported hypertension, nearly double previous national estimates. Male gender, age ≥ 30 years, and family history were significant risk factors, along with smoking, alcohol use, sedentary lifestyle, and unhealthy diet, while physical activity and dietary modification were protective. Despite high prevalence, only 22.1% had controlled blood pressure and 17.8% adhered to medication, with 51.5% relying on herbal remedies. Conclusions: These findings highlight the urgent need for early screening, youth-focused awareness, and culturally tailored interventions to reduce hypertension and prevent long-term cardiovascular complications. Hypertension among young adults in the UAE is a major public health concern, requiring integrated strategies combining education, lifestyle modification, and medical management to improve outcomes. Full article

Selenium (Se), a vital trace element, plays a significant role in maintaining vascular health and may offer protective effects against atherosclerosis. Its actions are mediated through Se-dependent selenoenzymes and selenoproteins, which enhance antioxidant defense, modulate inflammatory responses, and promote autophagy. These processes collectively help prevent cellular senescence—a state associated with age-related vascular decline characterized by oxidative stress, DNA damage, pro-inflammatory activity, and endothelial dysfunction. Epidemiological evidence consistently shows that low Se status is associated with increased risk of atherosclerotic cardiovascular disease within a narrow concentration range. However, clinical trials have not demonstrated clear reductions in cardiovascular events or mortality with Se supplementation alone. Overall, current evidence indicates that Se modulates key mechanisms involved in vascular aging and atherosclerosis, particularly redox balance, immune activation, and vascular cell homeostasis. This comprehensive review summarizes current epidemiological, clinical, and experimental research on the role of Se in cardiovascular health. It underscores Se’s potential as a promising strategy for the prevention and treatment of atherosclerosis, while also acknowledging the complexities and nuances of its effects on vascular health. A deeper understanding of the cellular and molecular mechanisms involved could pave the way for targeted interventions aimed at reducing the burden of atherosclerotic cardiovascular disease. Full article

Dementia, including Alzheimer’s disease (AD), represents one of the most pressing public health challenges of the 21st century, affecting more than 55 million individuals worldwide, with projections reaching 139 million by 2050. Current pharmacological treatments offer limited efficacy and significant side effects, driving intense interest in plant-derived natural products as both preventive and therapeutic agents. This review synthesizes preclinical and clinical evidence for key phytochemical classes, including polyphenols, phenolic acids, flavonoids, terpenoids, and alkaloids, in the context of dementia and age-related cognitive decline. Molecular mechanisms are examined in detail, including effects on antioxidant defense and redox homeostasis, suppression of neuroinflammation, and enhancement of synaptic plasticity and neurotransmission. Despite promising preclinical and epidemiological evidence, most clinical trials remain limited in scale and duration and provide mixed results on the efficacy of using phytochemicals for cognitive health. Among the compounds with the most consistent clinical support are the ginkgo diterpene extract EGb 761, saffron carotenoids, curcumin, and rosmarinic acid. A dedicated section addresses the emerging evidence for aromatherapy as a non-pharmacological intervention for behavioral and cognitive symptoms of dementia. Future directions include strategies to improve bioavailability of phytochemicals, the utilization of aromatherapy together with oral supplements, and the need for larger randomized controlled trials using well-characterized and reproducibly manufactured formulations and purified active compounds. Priority areas for future investigation include resolving pharmacokinetic barriers to central nervous system (CNS) delivery, standardizing herbal product composition, and conducting adequately designed clinical trials in well-defined patient populations. Full article

Aristolochic acid (AA), a naturally occurring compound found in Aristolochia plants, is a well-established nephrotoxin and Group 1 carcinogen. Emerging evidence suggests a potential link between AA exposure and hepatocellular carcinoma (HCC), one of the leading causes of cancer-related mortality worldwide. This review critically evaluates current knowledge on AA’s hepatic metabolism, its formation of persistent DNA adducts, and the induction of inflammatory responses in the liver. Based on preclinical and indirect human evidence, we propose a working hypothesis that AA may contribute to hepatocarcinogenesis through a dual mechanism: genotoxic (primarily via H-ras and p53 mutations resulting from AA-DNA adducts) and non-genotoxic (via chronic inflammation involving IL-6, TNF-α, and NF-κB activation, as well as epithelial–mesenchymal transition). We note, however, that these mechanisms remain to be validated in human cohorts and do not yet establish causality. Recent studies have identified novel mechanisms, including PDK4-mediated mitochondrial dysfunction, ferroptosis inhibition via p53 hijacking, and ARID1A deficiency as a susceptibility factor. A recent meta-analysis quantified a significantly increased risk of liver cancer following AA exposure in epidemiological studies. While direct causal evidence in humans remains limited, the high mutational burden observed in AA-exposed liver tissues warrants caution. Nevertheless, the primary public health priority pertains to the prevention of AA exposure. Further epidemiological and mechanistic studies are urgently needed. Full article

Background: Diabetes is a growing public health crisis across the Arab region, where rapid urbanization, dietary transitions, and physical inactivity have contributed to some of the highest diabetes rates globally. Despite a growing recognition of the problem, most diabetes prevention efforts in the region remain small-scale or insufficiently adapted to the sociocultural realities of adults living in the UAE. Evidence-based diabetes prevention strategies, such as the United States’ Centers for Disease Control Diabetes Prevention Program (DPP), reduce the risk of developing diabetes but remain underutilized. Methods: The objectives of this study were to (1) describe the systematic cultural adaptation of the Evidence-based Intervention for Diabetes Prevention (EID) using the Framework for Reporting Adaptations and Modifications–Expanded (FRAME), and (2) assess the preliminary acceptability of the adapted materials through formative focus groups. Results: Materials were culturally tailored to address both deep and surface structures. Deep structure adaptations incorporated Arab cultural values, social norms, and religious practices, including Ramadan-specific content. The original 26-session curriculum was condensed to 12 weekly sessions based on prior research and stakeholder input. Surface-level adaptations included translation into Arabic and development of culturally relevant educational videos. Three formative focus groups (n = 7 total participants) provided preliminary findings of strong acceptability of simplified, culturally relevant, and digitally supported materials. Conclusions: This work will inform the adaptation of an evidence-based lifestyle change program aimed at preventing type 2 diabetes in high-risk individuals to better meet the needs of adults living in the UAE. While some countries have created their own national diabetes prevention efforts, like the United Kingdom, there is notably no similar program in the Arab world. Full article

Introduction: Congenital myasthenic syndrome (CMS) is a rare hereditary disorder of the neuromuscular junction caused by pathogenic variants that affect acetylcholine transmission. We report three pediatric cases with CMS, including a rare homozygous CHRNE mutation previously described only once, a novel CHRNE compound heterozygous variant, and two novel DPAGT1 variants associated with limb-girdle CMS (LG-CMS), thereby expanding the known genetic and phenotypic spectrum of the disorder. Case presentation: The first patient, a 4-year-old girl born to consanguineous parents, presented with bilateral ptosis and fatigable weakness since infancy. Whole-genome sequencing revealed a homozygous CHRNE variant, c.991C>T. The second patient, a 4-year-old boy born to non-consanguineous parents, presented with congenital bilateral ptosis and ophthalmoplegia without generalized weakness. Genetic analysis identified compound heterozygous CHRNE variants, c.905C>G and c.1040T>C. Both patients demonstrated marked improvement with pyridostigmine therapy. The third patient, a 3-year-old girl born to non-consanguineous parents, presented with severe limb weakness requiring assistance in walking and performing daily activities with minimal ocular involvement, suggesting a diagnosis of LG-CMS. Genetic testing identified two novel variants in the DPAGT1 gene in the compound heterozygous form, c.710G>T and c.858C>A. The initial response to pyridostigmine diminished over time. Conclusions: These cases underscore the phenotypic heterogeneity of CMS, even within the same genetic subtype, and expand the existing mutational spectrum of CHRNE and DPAGT1 genes. This study also highlights the essential role of molecular diagnosis in distinguishing CMS from other neuromuscular disorders. Early genetic confirmation facilitates genotype-targeted therapy, prevents inappropriate immunosuppression, and enables informed reproductive counseling. Full article

Zearalenone (ZEA) is a common contaminant in crops and animal feed. However, research on the effects of ZEA on animal mammary tissue is relatively limited. Sulforaphane (SFN) is a naturally active compound mainly derived from cruciferous vegetables (such as broccoli), with significant antioxidant and cytoprotective effects. The purpose of this study is the effect of SFN on ZEA-induced toxicity in bovine mammary epithelial cells (MAC-T). By treating MAC-T cells with different concentrations of ZEA and SFN for 24 h, the results showed that different concentrations of ZEA (10, 20, 40, 60, 80, or 100 μM) could inhibit MAC-T cell viability. Treatment with SFN at concentrations of 1, 2.5, and 5 μM had no significant effect on cell viability. The results of combined treatment with 10 μM ZEA and 1, 2.5, or 5 μM SFN showed that SFN could significantly reverse the decrease in cell viability caused by ZEA; reduce the increase in lactate dehydrogenase (LDH) release, reactive oxygen species (ROS), and malondialdehyde (MDA) content induced by ZEA; and increase the levels of glutathione (GSH), superoxide dismutase (SOD), and mitochondrial membrane potential that were decreased by ZEA. SFN can significantly inhibit the upregulation of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) induced by ZEA exposure and markedly reverse the increase in cell apoptosis rate caused by ZEA. Compared with the control group, the expression of genes nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase 1 (GPX1) was significantly reduced in the ZEA group, while the addition of SFN effectively increased the expression levels of these genes. Corresponding protein detection results were consistent with the trends in gene expression. This study demonstrated that SFN alleviates ZEA-induced damage to MAC-T cells by activating the Nrf2 pathway, providing a theoretical basis for the subsequent application of SFN in dairy farming to prevent and control breast health risks related to mycotoxins. Full article

Preterm birth is a major cause of neonatal morbidity and mortality, and many spontaneous cases remain idiopathic. Increasing evidence suggests that intrauterine inflammation may occur in the absence of detectable infection, leading to the recognition of sterile intrauterine inflammation as an important mechanism contributing to threatened preterm labor and spontaneous preterm birth. This review summarizes current knowledge regarding the role of damage-associated molecular patterns (DAMPs), alarmins, pattern recognition receptors, inflammasome activation, cellular senescence, and pyroptosis in the initiation of sterile inflammatory pathways associated with labor. Key mediators including HMGB1, IL-1α, fetal cell-free DNA, platelet-activating factor, and S100 proteins appear to promote inflammatory activation within fetal membranes and the amniotic cavity. The review also discusses the emerging contribution of fetal immune activation, maternal–fetal immune dysregulation, maternal microchimerism, and epigenetic mechanisms to idiopathic preterm birth. Current diagnostic and therapeutic options remain limited, and no targeted treatment for sterile intrauterine inflammation has yet been established. Future approaches may include precision biomarkers, multiomics-based risk stratification, targeted immunomodulatory therapies, and modulation of maternal–fetal immune interactions. Improved understanding of sterile inflammatory mechanisms may ultimately support development of personalized strategies to prevent preterm birth and improve perinatal outcomes. Full article

Human activity recognition (HAR) plays a multi-dimensional supporting role in the medical field, providing strong technical support for various aspects such as disease prevention, diagnosis, treatment and rehabilitation. However, the use of traditional federated learning to deploy HAR models on edge devices is not ideal because of the heterogeneity of hardware and data. To solve this problem, this paper introduces a personalized HAR method, which can remove the outlier nodes and cluster hierarchically. In this study, the cosine similarity of local model parameters is calculated, and the clustering of dynamic clients is realized. In the study, the normalized training loss evaluation mechanism is introduced to identify and eliminate outlier nodes, and the robustness of the system is enhanced. In the study, the collaborative training method is adopted to meet the personalized needs of users and improve the generality of the model. The proposed method achieves an average recognition accuracy of 92.94% and an F1 score of 91.28% on four public datasets, demonstrating that the method put forward in this paper can reduce the negative impact of data heterogeneity, improve the efficiency of convergence, and produce good recognition performance for the development of the Internet of Things. Full article

Tidal flats are shrinking and eroding due to sea-level rise and human activities. Ecological submerged breakwaters (ESBs) offer a novel solution combining coastal protection and ecological restoration, but their effects on sediment dynamics lack field evidence. This study presents synchronous in situ measurements from an inner tidal flat (WN01) and an outer shallow area (WN02) of a newly built riprap slope-type ESB on the northern coast of the Sheyang River Estuary, Jiangsu, China. Using Acoustic Doppler Velocimeters (ADVs) and wave-tide gauges, we examined hydrodynamics, suspended sediment concentration (SSC), bed shear stress, erosion–accretion, and sediment transport under normal-weather and strong wave events. Within the constraints of a 14-day observation at two stations, our results indicate that: (1) The ESB reduced wave height and weakened currents, shifting dominant bed shear stress from wave-dominated outside to tide-dominated inside. Under normal weather, both sides were accretive. (2) Strong wave events caused sharp increases in bed shear stress, net erosion on both sides, and a 2–3-fold SSC rise, breaking the normal balance. (3) Suspended sediment transport direction remained northwest inside during strong wave events but shifted to northeast/southeast outside, demonstrating effective isolation of wave-driven anomalies. Bedload was trapped inside, resulting in no net sediment loss, in contrast to the unprotected southern tidal flat. (4) We recommend moderately lowering the ESB crest elevation to prevent excessive accretion and implementing “grey-green” restoration (salt marshes or oyster reefs) to enhance coastal resilience against sea-level rise. Full article

Background/Objectives: Bleomycin is an antineoplastic antibiotic used in the management of various malignancies. Nevertheless, its benefits are constrained by the development of pulmonary fibrosis. Amentoflavone, a biflavonoid, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, antioxidant, and antitumor effects, whereas alogliptin possesses antioxidant and anti-inflammatory properties. This study aimed to assess the potential protective effects of alogliptin and/or amentoflavone in a murine model of bleomycin-induced pulmonary fibrosis and to clarify the underlying mechanisms. Methods: Fifty male C57BL/6 mice were randomly divided into 5 equal groups: control, bleomycin, bleomycin + alogliptin, bleomycin + amentoflavone, and bleomycin + alogliptin + amentoflavone. The assessed endpoints included lung weight/body weight index, lung tissue fibrotic mediators, oxidative stress parameters, proinflammatory cytokines, and pyroptotic and autophagy mediators. Also, the bronchoalveolar lavage fluid (BALF) was evaluated for total and differential leukocytic counts and lactate dehydrogenase (LDH) activity. Moreover, vascular responses to potassium chloride, phenylephrine, and carbachol, together with tracheal responses to carbachol were determined. Lung tissues were further examined histopathologically and immunohistochemically. Results: Treatment with alogliptin and/or amentoflavone significantly decreased the lung weight/body weight index and BALF LDH activity, concomitant with mitigation of lung tissue oxidative stress parameters, fibrotic mediators, apoptosis, and pyroptosis with a significant augmentation of autophagy signals, alongside marked improvement in the lung architecture and vascular and airway reactivity compared with the bleomycin group. These effects were most pronounced with animals treated with the alogliptin/amentoflavone combination. Conclusions: These findings suggest that combined alogliptin and amentoflavone may constitute a promising strategy to prevent bleomycin-induced lung fibrosis. Full article

Background: Arterial hypertension (AH) remains a leading modifiable risk factor for cardiovascular disease. Although the inverse association between physical activity (PA) and AH is well established, practice-based evidence from consecutive primary care populations remains clinically relevant for evaluating how this association appears under routine healthcare conditions. Methods: This retrospective cross-sectional study evaluated the association between self-reported PA and clinically defined AH in 1284 adult patients from routine primary care practice. PA was categorized according to World Health Organization recommendations as low (<150 min/week), moderate (150–300 min/week), or high (>300 min/week). AH was defined as a documented clinical diagnosis and/or ongoing antihypertensive treatment. Logistic regression was used to assess associations between PA category and AH, with adjustment for age, sex, body mass index (BMI), and LDL-C. Results: AH was present in 41.2% of the study population. AH prevalence differed significantly across PA categories, decreasing from 55.9% in the low PA group to 40.8% in the moderate PA group and 26.7% in the high PA group (p < 0.001). Compared with low PA, moderate and high PA were associated with lower odds of AH in crude analysis (OR = 0.54, 95% CI: 0.41–0.71; and OR = 0.29, 95% CI: 0.21–0.39, respectively). These associations remained significant after adjustment for age, sex, BMI, and LDL-C. Conclusions: Higher self-reported PA was associated with lower prevalence of clinically defined AH in consecutive primary care patients. The main contribution of this study is the replication and quantification of this established association in a real-world primary care cohort using pragmatic PA categories and routinely documented AH. Because of the cross-sectional design, these findings should be interpreted as associations and do not establish causality or directionality. Broader physiological and self-regulatory capacity may represent a hypothesis-generating direction for future research, but these processes were not directly measured in this study. Full article

Background: Acute compartment syndrome (ACS) is a limb-threatening surgical emergency most commonly associated with fractures or high-energy trauma. Non-fracture-related ACS in athletes is uncommon and may lead to delayed diagnosis. Repetitive blunt trauma during combat sports has rarely been described as a potential mechanism. Case Methods: The case concerns a 21-year-old elite-level kickboxing athlete who developed acute compartment syndrome of the left lower leg following repeated calf kicks sustained during sparring. The patient presented with rapidly progressive calf pain, swelling, compartment firmness, paresthesias and weight bearing difficulties. CT angiography demonstrated diffuse edema of the posterior compartments associated with a large intramuscular soleus hematoma without active arterial bleeding. Results: In view of the severity of the symptoms and the characteristic clinical presentation, an emergency fasciotomy was performed in operating room. Progressive closure was achieved using the vessel loop shoelace technique, allowing gradual tension-free closure. Wound healing progressed without infection, and physiotherapy was introduced with joint mobilization. The patient achieved full functional recovery after 6 months. Conclusions: This case illustrates an atypical etiology of ACS—repetitive targeted calf strikes—and underscores the importance of early recognition even in the absence of fracture or major trauma. Clinical vigilance remains paramount, and prompt surgical intervention is critical to prevent irreversible muscle and nerve damage. Awareness of such mechanisms is particularly relevant for clinicians managing athletes in combat sports. To our knowledge, this is the first documented case of ACS secondary to repeated calf kicks in kickboxing. Full article