Honey is a natural product rich in phenolic compounds that contribute to its antioxidant and anti-inflammatory properties. The present study aimed to evaluate the biological activities of honey samples collected from different regions of Kazakhstan through experimental assays and computational analyses of major honey-derived phenolic compounds. Ethanolic extracts of seven honey samples were prepared and assessed for extraction yield, total phenolic content, total flavonoid content (TFC), antioxidant activity using the DPPH radical scavenging assay, and anti-inflammatory activity using the albumin denaturation inhibition assay. In addition, five representative honey-derived phenolic compounds, namely fumaric acid, p-hydroxybenzoic acid, p-coumaric acid, trans-2-hydroxycinnamic acid, and chrysin, were subjected to comprehensive in silico analyses including ADME prediction, drug-likeness evaluation, toxicity assessment, and multitarget molecular docking. Extraction yields ranged from 6.8% to 8.7%. The highest total phenolic content was observed in sample B12 (80.1 ± 9.7 mg GAE/g extract), whereas the highest TFC was detected in sample B10 (6.8 ± 0.5 mg quercetin equivalent (QE)/g extract). DPPH radical scavenging activity revealed IC50 values ranging from 2.5 ± 0.1 to 5.6 ± 0.4 mg/mL, with samples B11, B12, and B10 exhibiting the strongest antioxidant activities. In the albumin denaturation assay, all extracts demonstrated concentration-dependent anti-inflammatory activity, with inhibition percentages reaching 33.9% ± 2.0% at 100 mg/mL. The ADME analysis revealed that all investigated compounds exhibited favorable drug-likeness properties and high predicted gastrointestinal (GI) absorption. Chrysin demonstrated the highest lipophilicity and receptor-binding potential, whereas p-coumaric acid and trans-2-hydroxycinnamic acid showed the most balanced pharmacokinetic profiles. Toxicity predictions performed using ProTox-3.0, pkCSM, and admetSAR indicated low risks of hepatotoxicity and nephrotoxicity, with no predicted neurotoxicity, respiratory toxicity, carcinogenicity, or mutagenicity for any of the compounds. Molecular docking analyses against multiple inflammation-related targets, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and protein kinase B (AKT1), demonstrated strong binding affinities, particularly for trans-2-hydroxycinnamic acid and chrysin. These compounds exhibited favorable interactions with several key mediators of inflammatory signaling, suggesting potential multitarget mechanisms of action. Computational analyses demonstrated favorable drug-likeness characteristics and high predicted GI absorption for all investigated compounds. Toxicity predictions indicated low risks of hepatotoxicity and nephrotoxicity, with no predicted neurotoxicity, respiratory toxicity, carcinogenicity, or mutagenicity. Molecular docking analyses against multiple inflammation-related targets, including COX-2, iNOS, NF-κB, TNF-α, IL-6, and AKT1, identified trans-2-hydroxycinnamic acid and chrysin as the compounds with the strongest binding affinities, suggesting their potential role as multitarget modulators of inflammatory signaling pathways. Overall, the combined experimental and computational findings demonstrate that Kazakhstan honey represents a valuable source of bioactive phenolic compounds with promising antioxidant and anti-inflammatory properties. Among the investigated compounds, trans-2-hydroxycinnamic acid, p-coumaric acid, and chrysin emerged as the most promising candidates for further pharmacological investigation. These findings provide a scientific basis for future studies exploring honey-derived phenolics as potential complementary agents for the management of inflammatory disorders. The integration of experimental bioactivity assays with multitarget computational analyses provides novel insights into the mechanisms through which honey-derived phenolics may contribute to the therapeutic potential of honey.
Male reproductive health faces mounting concern as global sperm concentration (SC) has declined markedly, with evidence linking this trend to environmental and lifestyle factors rather than natural variability. In parallel, rising rates of obesity, diabetes, and hypertension point to shared mechanisms with infertility, particularly those rooted in diet. High intake of processed sugars, especially high-fructose corn syrup (HFCS), contributes to metabolic dysfunction, oxidative stress, hormonal imbalance, and inflammation, all of which can impair sperm function and disrupt the hypothalamic-pituitary-gonadal (HPG) axis. Unlike glucose, fructose undergoes hepatic metabolism, fostering insulin resistance, fat accumulation, and nonalcoholic fatty liver disease (NAFLD), further aggravating reproductive risks. In this review, four models of obesity, the energy balance model (EBM), carbohydrate-insulin model (CIM), obesogen model, and OBS/REDOX model, are applied to explain how excess fructose and obesogenic exposures drive metabolic dysfunction, oxidative stress, and endocrine disruption. Collectively, these processes reduce testosterone levels, impair spermatogenesis, compromise sperm quality, and may even induce epigenetic alterations transmissible to future generations. With modern diets increasingly dominated by HFCS and ultra-processed foods (UPFs), understanding fructose's role in reproductive decline is crucial for developing effective interventions. This review underscores the need for further research to clarify how dietary fructose and environmental obesogens jointly shape metabolic and reproductive health, offering insights into public health strategies aimed at protecting male fertility in the face of modern lifestyle challenges.
Both oxidative stress and inflammation are considered the driving mechanisms in most liver pathologies. Therefore, identifying pharmacological compounds with antioxidant and anti-inflammatory properties is central to curbing hepatic diseases. Ebselen is a synthetic organoselenium compound with glutathione peroxidase (GPx)-like activity, demonstrating potent antioxidant and anti-inflammatory effects experimentally. Ebselen targets several molecular mechanisms involved in hepatic cellular injury. It maintains redox-sensitive signaling, neutralizes reactive free radicals, and regulates thiol-dependent enzymes in experimental models of drug-induced, ischemia-reperfusion, and metabolic liver diseases. Studies provided experimental evidence for Ebselen's role in suppressing lipid peroxidation, preserving mitochondrial dynamics, inhibiting inflammatory response, and protecting hepatocytes in cell lines as well as murine models of different liver injuries. Findings also reported an indirect effect on cellular demise and fibrogenesis through inhibiting the activation of hepatic stellate cells (HSCs) and decreasing collagen deposition. The hepatoprotective effects of Ebselen also extend to include reducing hepatic lipid accumulation and preventing steatosis induction in rodent models of liver fibrosis. This review summarizes the current available evidence on the hepatoprotective effects of Ebselen.
BACKGROUND:Actin-like 7A (ACTL7A) is a testis-specific cytoskeletal protein essential for spermiogenesis, acrosome formation, and oocyte activation. Given its critical role in sperm integrity and fertilization, ACTL7A protein may be particularly susceptible to oxidative and thermal stress associated with varicocele. This study aimed to evaluate ACTL7A gene, and protein expression in the sperm of infertile men with varicocele. METHODS:Semen samples from infertile men with varicocele (n = 35) and fertile controls (n = 35) were assessed for standard sperm parameters (WHO 2021), redox status (2',7'-dichlorodihydrofluorescein diacetate [DCFH-DA] and BODIPY probes), chromatin packaging (Chromomycin A3 [CMA3] and Aniline Blue staining), DNA integrity (Sperm Chromatin Structure Assay [SCSA]), ACTL7A gene, and protein expression (quantitative real-time PCR and Western blotting). RESULTS:Compared to fertile controls, the varicocele group exhibited significantly lower sperm quality, elevated oxidative stress, increased lipid peroxidation, and greater chromatin immaturity and DNA fragmentation (p < 0.01). Notably, ACTL7A gene and ACTL7A protein expression levels were significantly reduced (p < 0.05), with inverse correlations observed between ACTL7A gene and markers of chromatin packaging defects, including protamine deficiency and residual histones (p < 0.05). CONCLUSION:ACTL7A gene expression and ACTL7A protein are significantly reduced in sperm from men with varicocele, likely causing defective chromatin remodeling and abnormal sperm head formation. This study first links varicocele-associated oxidative stress to ACTL7A, suggesting its potential as a biomarker of testicular dysfunction. Future research should explore whether interventions like antioxidant therapy, varicocelectomy, or varicocele severity and duration improve sperm quality and reproductive outcomes.
Chronic oxidative stress has long been implicated in renal pathologies, but whether sustained oxidative damage primarily promotes chronic kidney disease (CKD) or tumorigenesis remains unclear. To address this question, we investigated the long-term effects of oxidative stress on human embryonic kidney (HEK293T) cells chronically exposed to a low dose of hydrogen peroxide (H2O2, 50 μM H2O2) for 9 months, generating two adapted lines, 50R30 and 50R45. These cells exhibited enhanced survival and tolerance to acute high-dose H2O2 challenge, indicating an oxidative stress-resistant phenotype. Despite this adaptation, both cell lines showed markedly reduced proliferation and migration, reflecting loss of cellular vitality and function typical of renal degeneration. Transcriptomic and protein analyses revealed upregulation of genes and proteins involved in cell-cycle arrest (p53 and p21), senescence, and the NF-κB/IL-6-driven senescence-associated secretory phenotype (SASP), oxidative stress responses, together with elevated heat shock factor 1 (HSF1) expression indicative of biomolecular damage and impaired adaptive capacity. Collectively, these findings suggest that chronic oxidative stress drives cellular aging and dysfunction rather than malignant transformation, leading to degenerative changes resembling CKD pathology. Moreover, prolonged oxidative stress alone appears insufficient to induce carcinogenic transformation; additional genetic or epigenetic alterations, together with specific cellular machinery, are likely required to drive kidney malignancy. This study therefore provides mechanistic insight into how sustained oxidative stress promotes renal cell senescence and contributes to CKD progression.
Heat stress (HS) is a growing public health concern as rising global temperatures and occupational hazards expose a significant portion of the world's population to extreme heat. The kidneys are particularly vulnerable to heat-induced injuries, with oxidative stress (OS) playing a central role in their pathogenesis. The process involves heat-induced mitochondrial dysfunction and stimulation of inflammatory pathways. This leads to the production of excessive reactive oxygen species (ROS) that eventually overwhelm the kidney's natural antioxidant defenses. The resultant OS directly damages lipids, proteins, and DNA in renal tubular cells, a condition that is worsened by systemic inflammation and renal hypoxia. Although cells initially activate protective mechanisms involving heat shock proteins (HSPs) to preserve mitochondrial integrity, prolonged heat exposure undermines these defenses, increasing stress and triggering apoptotic pathways. This article focuses on the impact of HS on kidney health and the role of OS in the pathogenesis of heat-induced kidney injuries. Key markers of heat-induced OS, such as lipid peroxidation products (e.g., malondialdehyde [MDA], F2-isoprostanes, 4-hydroxynonenal [4-HNE], and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) and their effects on hematological indices and inflammatory response are highlighted. Ultimately, clarifying these specific mechanisms is essential to guide the development of early diagnostic tools and targeted treatments. This will help to reduce kidney damage, especially in vulnerable populations. We suggest that strategies such as adequate hydration, educating vulnerable groups on signs of heat strain, wearing light clothing, and heat acclimatization can mitigate the adverse effects of the rising global temperatures on kidney health.
BACKGROUND:Nutrition is a key modifiable factor supporting mitochondrial health and is essential for ovarian function and women's health across the life course. From menarche to menopause, mitochondrial efficiency underpins physiological balance. The menopausal transition is particularly critical, as hormonal and neuroendocrine changes are associated with impaired mitochondrial function and increased risk of age-related disorders. AIM:This review aimed to systematically review and synthesize the available evidence on mitochondrial function across in vitro, animal, and human studies and to evaluate the potential protective role of vitamins and nutrients in maintaining mitochondrial health, with attention to sex-specific findings. METHODS:A systematic search was conducted across multiple electronic databases. Forty-six eligible studies were identified and critically reviewed for evidence on mitochondrial function, sex-based differences, and nutritional influences. RESULTS:Mitochondrial dysfunction may contribute to the pathophysiology of age-related disorders, including osteoporosis, cardiovascular disease, neurodegenerative conditions, and cancer. Nutritional factors are crucial for preserving mitochondrial integrity. Vitamins C, E, and D, NAD + precursors such as nicotinamide riboside, coenzyme Q10, MitoQ, fucoxanthin, and cabergoline reduce oxidative stress, enhance mitochondrial biogenesis, support electron transport chain activity and ATP production, and maintain redox balance. These actions promote mitochondrial resilience and cellular energy metabolism. Evidence further indicates that women, particularly during the menopausal transition, exhibit heightened vulnerability to mitochondrial dysfunction, highlighting the relevance of nutrition-based interventions. CONCLUSION:Optimizing dietary intake of vitamins, antioxidants, and mitochondrial cofactors is a cost-effective, accessible strategy to support mitochondrial health and reduce age-related disease risk in women.
Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various cellular events, playing critical roles in the physiology of myofibroblasts. However, when dysregulated, these molecules can engage in misinstructive manners with myofibroblasts, directing these cells toward pathogenic states and behaviors. In brief, dysregulated ROS pathologically modulate myofibroblast differentiation, extracellular matrix (ECM) remodeling, and immune evasion, maintaining self-perpetuating cycles of myofibroblast survival. The mediation of ROS promotes maladaptive intra and extracellular responses that contribute to myofibroblast persistence by enhancing ECM stiffness, increasing resistance to apoptosis, inducing senescence, and impairing immune clearance. ROS-mediated alterations in ECM components, most notably in proteoglycans (PGs) and glycosaminoglycans (GAGs), further dysregulate the ECM and make it more conducive to myofibroblast persistence. Additionally, ROS-induced immune privilege mechanisms prevent the proper clearance of myofibroblasts. Therefore, targeting ROS collectively offers promising therapeutic potential for mitigating their pathological presence and behavior, thereby enhancing overall corneal recovery following insults.
The present document highlights the significance of microbial lipids as new generation anticancer, antitumor, and antioxidant compounds. It focuses on the diverse nature of the action of these lipids in cancer treatment, especially polyunsaturated fatty acids (PUFAs). These mechanisms include membrane disruption, apoptosis/necrosis, DNA damage modifying histone and gene expression, angiogenesis inhibition, cell proliferation/cycle regulation, migration, invasion, metastasis, differentiation, reversal of drug resistance, and immune system modulation. The text also discusses the economical biosynthesis of these lipids via microbial fermentation, chemosynthesis, and other synthesis techniques. The versatility of PUFAs is described in detail in the following areas of study including signal transduction and inflammation. While microbial lipids offer potential cost-effectiveness due to scalable fermentation processes, it is important to note that specific clinical dosage regimens and comprehensive pharmacoeconomic comparisons with standard chemotherapeutic agents are still under investigation. Current estimates suggest lower long-term costs if optimized dosing is achieved, but further clinical trials are required to validate these economic benefits.
Mitochondria are intracellular organelles that regulate cell survival and death. Hyperglycemia modulates the functioning of the mitochondria in endothelial cells. We discovered that high-glucose (HG) treatment reduces FUN14 domain-containing 1 (FUNDC1) expression in endothelial cells. FUNDC1 expression in the mitochondria inhibits the proteasomal degradation of cytochrome C oxidase IV (COX-IV) and regulates mitochondrial complex I and IV activities as well as ATP synthesis under normal conditions. The FUNDC1 depletion in HG contexts affects mitochondrial complex I and IV activity as well as ATP synthesis and promotes mitochondrial damage through the loss of mitochondrial membrane potential and the production of reactive oxygen species (ROS). BAM15 is a mitochondrial uncoupler that increases mitochondrial function and endothelial survival. Cotreatment with HG and BAM15 increased the FUNDC1 protein expression level and the mitochondrial translocation of FUNDC1 in HG-treated cells. The BAM15-induced upregulation of FUNDC1 expression increased the mitochondrial expression of COX-IV, complex I and IV activity, and ATP synthesis. Our findings suggest that FUNDC1 expression in endothelial cells under hyperglycemic stress plays a crucial role in limiting vascular damage and apoptotic cell death. We discovered a mechanism through which BAM15 protects endothelial cells through FUNDC1-mediated mitophagy and metabolic regulation. Targeting FUNDC1 via mitochondrial uncoupling is a promising therapeutic strategy for treating diabetic vascular diseases.
