Search Results (10,955)

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies. Full article

Objective: To evaluate the efficacy of NADPH oxidase 4 and miR-146a-5p in current treatment planning for ascending aortic aneurysms, independent of aortic diameter, and to develop protocols that will ensure the treatment of ascending aortic aneurysms, which pose a risk for aortic dissection, without complications. Methods: Patients who met the inclusion criteria and underwent surgery at Dr. Siyami Ersek Chest, Heart, and Vascular Surgery Training and Research Hospital for ascending aortic aneurysms and coronary artery disease between 2023 and 2024 were included in the study. This study was designed as a prospective study. Demographic, biochemical, radiological, and echocardiographic data were collected, and NOX4 mRNA and miR-146a-5p expressions were examined and compared in tissue samples. Results: The study was conducted on a total of 50 patients, with 25 patients in the aneurysm group and 25 patients in the control group. miR-146a-5p expression levels were found to be significantly decreased in the patient group compared to the control group (p = 0.001). When NOX4 mRNA expression levels were examined, no significant difference was found between the control and aneurysm groups. No correlation was found between NOX4 mRNA and miR-146a-5p levels (p = 0.764). When the relationship between ascending aorta diameter and both NOX4 mRNA and miR-146a-5p was examined, it was found that miR-146a-5p expression was negatively correlated with ascending aorta diameter (p = 0.036) and did not show a significant correlation with NOX4 mRNA levels (p = 0.318). A similar correlation was also found with ascending aorta length. The correlation of NOX4 mRNA and miR-146a-5p expression levels with age, gender, and ejection fraction was investigated separately. No significant correlation was found for all three variables. The optimum cut-off value to be used to separate the patient group from the control group using miR-146a-5p expression levels, as well as the sensitivity and specificity of miR-146a-5p expression levels when this cut-off value was used, was calculated using an ROC curve. Specificity for miR-146a-5p expression was found to be 88%, and sensitivity was found to be 66%. Conclusions: The study found promising results indicating that NOX4, shown to be a determinant of vascular oxidative stress, is not involved in the development of ascending aortic aneurysms; however, miR-146a-5p, which functions in the regulation of many inflammatory responses, including the regulation of NOX4 expression, may help prevent the development of ascending aortic aneurysms. Further studies aimed at elucidating the genetic and biochemical processes involved in aneurysm development suggest that miR-146a-5p could be a therapeutic target for preventing aneurysms. Full article

This study evaluates regulated deficit irrigation (IR) and post-harvest dehydration (DH) as complementary strategies to mitigate extreme thermal stress on the red grape variety Avgoustiatis during the hot 2024 vintage. Analysis of the berries reveals that while IR significantly expanded vine productivity to 2.75 kg/vine compared to 1.32 kg/vine recorded in control vines (CO), it successfully maintained berry weight (240 g). Conversely, DH induced controlled water loss, reducing berry weight to 93 g and concentrating must sugars to 27.3 ^°Brix, relative to the 23.2 ^°Brix observed in IR. Crucially, both IR and DH prevented the thermal degradation of total acidity (6.73 g/L and 7.25 g/L respectively) which caused by heat stress in CO samples (6.21 g/L). In the finished wines, both practices increased colour intensity by lowering anthocyanin extractability. However, chemical profiling clearly differentiated the treatments with DH maximized skin tannins (164.7 mg/L), yielding highly structured, astringent wines characterized by plum aromas driven by elevated nerol content (492.91 μg/L). Conversely, IR wines presented a more complex volatile profile, boosting fruity and floral notes. In conclusion, as irrigation becomes increasingly restricted by water scarcity under climate change, post-harvest dehydration offers an effective alternative for producing premium, structurally dense red wines. Full article

Eating behavior and eating habits are shaped from the earliest stages of life through interactions among biological, familial, social, and environmental factors. The aim of this narrative review is to integrate evidence on the early-life determinants of eating behavior and their influence on dietary intake from infancy to adolescence. A narrative review was conducted with a structured search approach prioritized on longitudinal studies, intervention trials, and policy evaluations when available, and using cross-sectional evidence mainly to describe patterns and sociodemographic factors. Synthesizing the current evidence, our framework proposes that breastfeeding, responsive complementary feeding, and self-regulatory parenting are associated with higher responsiveness to internal hunger, satiety cues, and preference for nutrient-dense foods. Conversely, coercive practices, early exposure to highly palatable foods, and the influence of food marketing are linked to dominant hedonic responses and impulsive consumption patterns. Furthermore, family environments characterized by stress or food insecurity, together with high access to low-nutrient foods, may increase vulnerability to poor eating habits and emotional eating during adolescence. Overall, the evidence highlights the need for preventive interventions that integrate parenting support, school food education, digital marketing regulation policies, and the promotion of healthy food environments across multiple sectors. Understanding the biological, psychological, and social factors linking early determinants to dietary intake and eating behaviors across development is essential for promoting a balanced relationship with food and preventing chronic diseases from an early age. Full article

Behavioral epigenetics links experiences of adversity, stress, and care to molecular variation associated with health and behavior and can reshape understandings of embodiment across the life course. As such findings enter legal and policy debates, they raise pressing questions about how judges assess responsibility, weigh extralegal factors in sentencing, and govern the use of emerging scientific evidence. This article develops a framework of biological justice to guide the translation of epigenetic evidence into judicial decision-making without reintroducing biological determinism or naturalizing structural inequality. Integrating insights from epigenetics, sociology of science, bioethics, and criminal law, we clarify the inferential limits of current research and examine risks of biologizing inequality, predictive governance, and eugenic logics. We argue that epigenetic evidence should be restricted to contextual, defendant-protective, and rehabilitation-oriented uses in sentencing and post-conviction proceedings, while predictive and coercive applications should be explicitly excluded. Overall, this framework emphasizes structural framing, community oversight, and equity to prevent molecular accounts of adversity from reinforcing existing hierarchies. Full article

Copper sulphate pentahydrate is widely used in agriculture to control bacterial and fungal diseases in various crops. Despite its extensive application, limited data exist regarding its potential toxic effects on juvenile rats following early-life exposure. In addition to oxidative stress and inflammation, copper overload may also trigger cuproptosis, a recently identified copper-dependent form of regulated cell death. This study aimed to investigate the histopathological, biochemical, and molecular effects of copper sulphate exposure on major organs in juvenile rats and to elucidate the associated inflammatory and oxidative stress-related mechanisms. Male and female Sprague–Dawley rats (30–40 days old, 50–70 g) were randomly assigned to control and experimental groups. Following copper sulphate exposure, histopathological examinations were performed on major organs, including the liver, kidney, heart, lung, and reproductive tissues (testis in males and ovary in females). Immunohistochemical analyses of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB) were conducted. Oxidative stress parameters, including malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS), were measured using ELISA. Gene expression levels of TNF-α and NF-κB were evaluated by quantitative real-time PCR (qRT-PCR). Copper sulphate exposure induced significant histopathological alterations in all examined tissues of both male and female juvenile rats. Biochemical findings revealed increased oxidative stress, evidenced by elevated MDA and TOS levels along with altered TAS values. Furthermore, immunohistochemical and gene expression analyses demonstrated upregulation of TNF-α and NF-κB, indicating activation of inflammatory pathways. Copper sulphate exposure leads to widespread morphological changes in juvenile rats, potentially mediated by oxidative stress and inflammation. These findings provide insight into the biological impact of early-life pesticide exposure. Further studies are warranted to clarify the underlying molecular mechanisms and to develop effective preventive or therapeutic approaches. Full article

Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO₃)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO₃-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO₃-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H₂O₂) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47^phox/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO₃-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO₃-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO₃-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders. Full article

Background/Objectives: Occupation shapes time use, physical demands, stress, and access to health resources, yet it remains an understudied axis of inequality among working women in low- and middle-income countries. This study assessed occupational-group disparities in lifestyle behaviors and adiposity levels among Peruvian working women. Methods: We conducted a pooled repeated cross-sectional analysis of ten Peruvian DHS/ENDES rounds from 2014–2019 and 2021–2024 among working women aged 18–49 years. The exposure was standardized occupational group, using professional/technical/managerial workers as the reference. Outcomes included five lifestyle behaviors and four adiposity indicators. Crude models estimated descriptive prevalence ratios (PRs) or beta coefficients; secondary adjusted models included age group, survey year, education, wealth, residence, natural region, and marital status. Results: A total of 40,726 women were included. Agricultural workers showed lower crude prevalences of almost-daily television viewing (PR 0.49; 95% CI 0.47–0.52), current smoking (PR 0.14; 95% CI 0.10–0.19), current alcohol use (PR 0.39; 95% CI 0.36–0.42), and heavy alcohol use (PR 0.17; 95% CI 0.12–0.27); these contrasts attenuated but generally persisted after adjustment. Insufficient fruit and vegetable intake exceeded 87% in all groups. Sales, domestic/household, services, and skilled manual workers had higher adjusted obesity than the reference group, with adjusted PRs ranging from 1.22 to 1.35. Conclusions: Occupation identifies relevant heterogeneity in lifestyle behaviors and adiposity levels among Peruvian working women. Lifestyle and adiposity profiles did not follow a simple social gradient, supporting occupation-specific strategies for noncommunicable disease prevention. Full article

This study develops and validates risk-based emergency response scenarios for Biosafety Level 2 (BSL-2) and Animal Biosafety Level 2 (ABSL-2) facilities. Utilizing Bow-tie analysis, three multidimensional scenarios were constructed: infrastructure failure, biosecurity breach, and compound disaster. Four domain experts independently evaluated the scripts using the Content Validity Index (CVI), with an absolute consensus threshold of I-CVI = 1.00. To address operational gaps identified during initial evaluations, the revised protocols were strictly aligned with the Taiwan Centers for Disease Control (CDC) mandatory reporting thresholds for high-hazard incidents. Furthermore, the scripts explicitly defined the Incident Command System (ICS) to prevent communication fragmentation and integrated the NC3Rs tunnel handling technique to minimize occupational bite risks. Following these targeted refinements, all items achieved absolute expert consensus. This research translates static biosafety regulations into dynamic, stress-tested training tools. By providing a standardized instrument for resilience assessment, this study equips frontline personnel with the critical capacity to navigate cascading crises while strictly adhering to a “life safety first” paradigm. Full article

Severe subacute exposure to aluminium chloride (AlCl₃) impairs renal function and induces cortical tubular injury; however, the concomitant balance between injury and repair in tubular epithelia remains incompletely defined. Accordingly, we aimed to use a high-dose regimen of AlCl₃ (100 mg·kg⁻¹·day⁻¹ for 30 days, oral gavage) as a standardised renal stressor in male Wistar rats to quantify shifts along the injury–repair balance in the renal cortex and to test whether L-carnitine (LC) pretreatment (200 mg·kg⁻¹·day⁻¹) can attenuate these shifts. Twenty rats were assigned to four groups: control, LC alone, AlCl₃ alone, and LC followed 60 min later by AlCl₃. On day 31, we assessed body-weight gain, renal functional markers, blinded cortical lesion scoring, quantitative histochemistry, and immunohistochemical profiling of cleaved caspase-3 (apoptotic signalling) and Ki-67 (proliferative engagement) within the same cortical compartment. AlCl₃ exposure produced a severe renal stress phenotype compared with controls, reducing body-weight gain from 99.8 ± 8.6 to 24.0 ± 8.3 g and increasing serum urea and creatinine from 26.40 ± 3.21 to 48.60 ± 5.81 mg/dL and from 0.606 ± 0.063 to 0.956 ± 0.147 mg/dL, respectively. Cortical injury increased from 0 (0–0) in controls to 15 (15–15) after AlCl₃ exposure. AlCl₃ also reduced strong PAS area from 97.92 ± 1.10% to 52.37 ± 14.68% and protein optical density from 0.353 ± 0.020 to 0.269 ± 0.039, while increasing collagen area fraction from 6.92 ± 1.67% to 18.40 ± 3.02% and cleaved caspase-3 from 1.0 (1.0–2.0) to 12.0 (12.0–12.0). Ki-67 labelling declined from 17.80 ± 3.35% to 6.00 ± 1.58%, indicating suppressed proliferative engagement. Compared with AlCl₃ alone, LC pretreatment showed partial protection, with higher body-weight gain (70.0 ± 15.6 g), lower serum urea and creatinine (21.40 ± 2.30 mg/dL and 0.580 ± 0.084 mg/dL), lower cortical injury burden [3 (3–4)], greater strong PAS area (89.25 ± 2.67%), higher protein optical density (0.354 ± 0.012), lower collagen area fraction (12.26 ± 1.70%), lower cleaved caspase-3 [4.0 (4.0–6.0)], and higher Ki-67 labelling (10.60 ± 2.30%). Residual cortical injury, persistent collagen elevation, and incomplete Ki-67 preservation indicate that LC pretreatment attenuated, but did not fully prevent, AlCl₃-induced renal cortical alterations. Overall, high-burden AlCl₃ exposure not only enhanced cell loss but also impaired regenerative renewal, whereas LC pretreatment partially preserved this injury–repair balance. Full article

Not all sleep loss is equal, and overlooking this limits progress in sleep and neurological disease research. We compared nine rodent sleep deprivation paradigms, gentle handling, multiple platform variants, disk-over-water, the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm, novel object introduction, curling prevention by water, automated systems, and head-lifting, evaluating stress confounds, sleep stage specificity, chronicity, and neurobiological outcomes. Effects included hippocampal plasticity, prefrontal chemistry, glymphatic clearance, neuroinflammation, oxidative stress, neurogenesis, and circadian regulation, linked to Alzheimer’s, Parkinson’s, and psychiatric comorbidities. UCSD with caffeine produced antioxidant depletion, serotonin reduction, acetylcholinesterase upregulation, and synaptophysin loss, early neurodegeneration markers. We propose a disease-targeted framework with six translational priorities and reporting standards. Full article

Problematic smartphone use (PSU) has become an increasingly important public health concern among adolescents, yet the potential protective role of restorative environmental experiences (nature exposure) remains insufficiently understood. Under the perspective of Stress Reduction Theory (SRT) and Attention Restoration Theory (ART), this cross-sectional study examined the association between nature exposure and adolescent PSU, with anxiety and self-control tested as potential mediators. The sample comprised 700 high school students recruited from several high schools in Qinghai Province, China (52.00% female; M age = 17.01 years, SD = 0.78). Nature exposure, anxiety, self-control, and PSU were assessed using self-report measures. The results showed that nature exposure was negatively associated with PSU; anxiety and self-control significantly mediated this association both independently and sequentially. Specifically, more nature exposure was associated with lower anxiety and higher self-control, which, in turn, were associated with lower PSU. These findings suggest that restorative environmental experiences may be associated with reduced vulnerability to PSU through interconnected affective and self-regulatory processes. The present study extends existing literature by integrating emotional and attentional restoration perspectives within a unified framework linking nature exposure to adolescent PSU, and provides implications for the prevention and intervention of PSU. Full article

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification—diet, physical activity, sleep, and stress regulation—remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification. Full article

Paralympic Powerlifting is a maximal strength sport that requires high training intensity and efficient recovery to maintain performance and prevent injury. Intense training can induce oxidative stress, potentially compromising performance and physiological adaptation. Caffeine (CA) is a widely used ergogenic aid with potential to enhance muscle strength and reduce oxidative damage. This study investigated the acute effects of CA supplementation (9 mg/kg) on static strength indicators and oxidative stress markers in 14 male Paralympic powerlifting athletes. The protocol included two conditions (CA and placebo), with athletes performing 5 sets of 5 repetitions at 80% of 1 RM in the adapted bench press. Strength variables (maximal isometric force, 1-s peak force, and force variability) and biomarkers (TBARS/MDA, total antioxidant capacity, sulfhydryl groups, and uric acid) were analyzed. CA supplementation significantly increased maximal isometric strength, improved 1-s peak force, and reduced variability, suggesting enhanced motor unit recruitment. However, CA also led to increased oxidative stress, as evidenced by elevated TBARS levels, reduced antioxidant capacity, decreased sulfhydryl groups, and higher uric acid concentrations post-exercise. In conclusion, while CA acutely improves neuromuscular performance, it does not attenuate—and may even exacerbate—exercise-induced oxidative stress. Therefore, its use in strength sports should be approached with caution. Full article

Dementia, and more specifically Alzheimer’s disease (AD), is a progressive neurodegenerative disorder that has become a growing health menace in the world with an escalation in incidence as well as enormous social and economic consequences. Existing pharmacological treatment including cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists are not very effective in reducing the symptoms and fail to prevent the disease process. The non-pharmacological treatment interventions such as diet, exercise and cognitive training have supportive effects and cannot be used as standalone treatments. Therapeutic gap has resulted in increased interest in complementary and alternative therapies, especially that of pleiotropic action of herbal medicines. Bacopa monnieri (BM) is an Ayurvedic herb that has historically been used to treat memory enhancement and now has both preclinical and clinical evidence supporting its ability to modulate neurotransmission, reduce oxidative stress and suppress neuroinflammation. However, such difficulties as low bioavailability, instability of the environmental factors, and variations in formulations restrict its clinical applicability. New technologies with a lot of potential such as microencapsulation technology can provide the solution to this problem by increasing stability, solubility, and targeted delivery of compounds that will increase treatment efficacy. This narrative review is a synthesis of the existing information on the pathogenesis of dementia, therapeutic approaches, and the effectiveness of BM as a complementary intervention. It points out links between traditional medicine and modern neuroscience, strengths and limitations of on-going evidence, gaps that need further research, such as long-term clinical trials, standardized formulations, and discovery of the role of BM in the gut–brain axis. BM is a prime example of how herbal medicines can be used as a complement to conventional treatment and play a role in multi-modal approaches aimed at reducing the cognitive impairment associated with dementia. Full article