Search Results (10,340)

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains associated with poor prognosis despite multimodal treatment. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation and redox imbalance, has recently emerged as a potential therapeutic vulnerability in glioma. This review summarizes current knowledge on the molecular regulation of ferroptosis in glioma and discusses its implications for tumor progression, therapeutic resistance, and translational targeting. Methods: A structured narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, and Web of Science databases. Experimental, translational, and clinically relevant studies investigating ferroptosis-related mechanisms and therapeutic strategies in glioma and GBM were qualitatively analyzed. Results: Ferroptosis in glioma is regulated by interconnected pathways involving iron metabolism, phospholipid remodeling, oxidative stress, and antioxidant defense systems, particularly the SLC7A11–glutathione–GPX4 axis. Additional protective mechanisms mediated by FSP1 and DHODH, together with regulatory networks involving NRF2, ATF4, p53, and hypoxia-related signaling, contribute to adaptive resistance to ferroptosis. Increasing evidence indicates that ferroptosis interacts bidirectionally with the glioma tumor microenvironment and may exert both antitumor and immunosuppressive effects. Preclinical studies further suggest that ferroptosis induction may enhance the efficacy of temozolomide, radiotherapy, and immunotherapy, although clinical translation remains limited by tumor heterogeneity, blood–brain barrier penetration, and resistance mechanisms. Conclusions: Ferroptosis represents a biologically plausible and therapeutically promising target in glioma. Improved understanding of ferroptosis regulation, tumor microenvironment interactions, and biomarker-guided therapeutic strategies may support the future development of more effective treatments for GBM. Full article

Radiation-induced liver injury (RILI) is a major complication of abdominal radiotherapy, originating from mitochondrial oxidative stress, and effective radioprotectants are lacking. We designed an antioxidant intended to target mitochondria, TPP-C6-NIT, by conjugating a triphenylphosphonium cation to an imidazole nitroxide radical. Its protective effects were evaluated through in vitro assays, studies on irradiated L-02 and Huh-7 cells, a mouse model of whole-body irradiation, combined with metabolomics, molecular docking, and assessments of mitochondrial function, apoptosis, and inflammation. TPP-C6-NIT exhibited potent radical scavenging activity in vitro. In L-02 cells, it reduced oxidative stress, preserved mitochondrial function (membrane potential, ATP, respiratory capacity), and improved viability. In mice, pretreatment with TPP-C6-NIT significantly improved survival, alleviated liver injury (reduced serum ALT/AST and histopathological damage), and suppressed systemic inflammation. Mechanistic exploration suggested TPP-C6-NIT treatment was associated with increased Nrf2/GPX4 expression and reversal of lipid metabolic changes. Notably, TPP-C6-NIT did not confer significant protection in Huh-7 cells, indicating selective cytoprotection. By reducing oxidative stress and preserving mitochondrial function, TPP-C6-NIT demonstrates potent protection against radiation-induced liver injury in a whole-body irradiation mouse model, presenting a promising candidate for further development. Full article

Background/Objectives: Obesity-associated metabolic dysfunction involves oxidative stress, gut barrier impairment, and gut–liver axis disruption. This study evaluated whether enzymatically prepared Solenocera crassicornis peptides (SCPs) provide additional benefits during diet normalization in HFD-induced obese mice and examined associations with antioxidant, microbial, and barrier markers. Methods: SCPs were characterized using UPLC-Q-TOF-MS/MS and amino acid analysis. Peptides underwent bioactivity prediction and Keap1 docking. After 7 weeks of HFD feeding, obese male C57BL/6J mice were switched to a normal diet and administered vehicle, orlistat, or SCPs for 4 weeks. Adipose tissue mass, serum lipid profiles, liver histology, hepatic antioxidant status, barrier-associated histological and biochemical markers, and gut microbiota composition were assessed. A simulated digestion–fecal fermentation model was used to assess the effects of fermentation products generated in the presence of digested SCPs on H₂O₂-induced oxidative injury and MUC2 secretion in LS174T goblet-like cells. Results: SCPs reduced epididymal and perirenal fat, improved serum lipids, improved hepatic steatosis-related morphology and enhanced hepatic antioxidant status. SCPs were also associated with improved intestinal morphology, increased mucin-associated staining, decreased serum diamine oxidase levels and reduced hepatic lipopolysaccharide accumulation. 16S rRNA sequencing showed SCP-associated microbial shifts, with correlations linking taxa to metabolic and barrier markers. Fermentation products generated in the presence of digested SCPs improved oxidative-stress and MUC2-related readouts in LS174T cells. Conclusions: During diet normalization, SCPs were associated with additional improvements in adiposity, lipid profiles, hepatic antioxidant status, intestinal barrier readouts, and gut microbiota. These findings support further investigation of SCPs as standardized marine protein hydrolysates, but active components, causal mechanisms, long-term efficacy, safety, and human relevance remain to be established. Full article

Young barley, derived from the early vegetative stage of Hordeum vulgare L., constitutes a plant-based functional ingredient whose phytochemical profile differs markedly from that of mature grain. Two principal commercial forms exist—dried grass powder and juice-derived products—differing in matrix composition and bioactive compound concentration. This narrative review critically evaluates the current knowledge on the phytochemical composition, biological activity, and translational relevance of young barley preparations considered as a functional plant food. The phytochemical spectrum is dominated by C-glycosyl flavones, particularly saponarin and lutonarin, alongside phenolic acids, chlorophylls, enzymatic antioxidants, vitamins, and minerals. Experimental evidence implicates the modulation of redox homeostasis, inflammatory signaling, and metabolic regulators as the primary biological mechanisms. In vitro studies additionally demonstrate antiproliferative activity in human cancer cell lines and immunomodulatory properties mediated by polysaccharide-rich fractions, extending the biological profile of young barley beyond classical antioxidant activity. Although preclinical models consistently demonstrate antioxidant and metabolic effects, high experimental doses and limited preparation standardization restrict the direct extrapolation to human supplementation contexts. Available clinical trials suggest modest improvements in selected lipid, glycemic, and oxidative stress markers; yet, most are small in scale and brief in duration. Agronomic variables including fertilization strategy and soil composition represent additional, underappreciated sources of phytochemical variability and safety concern. Overall, the current evidence supports the biological plausibility of young barley as a functional plant food; yet, the clinical data remain preliminary. Future research should prioritize preparation standardization, dose–response characterization, and agronomic transparency to strengthen translational reliability. In conclusion, young barley preparations represent a biologically plausible functional plant food ingredient with preliminary clinical support, pending confirmation from adequately powered, standardised randomised controlled trials. Full article

The human APOE gene is polymorphic with three major alleles that encode apolipoprotein (apo) E2, apoE3, and apoE4. Both apoE2 and apoE4 are associated with increased atherosclerosis risk. This study utilized human APOE2, APOE3, and APOE4 gene replacement mice and single-cell RNA sequencing approach to delineate the mechanisms underlying this association. The human APOE2, APOE3, and APOE4 mice were fed a Western-type high fat–cholesterol diet for 16 weeks. Hyperlipidemia and significant atherosclerosis were observed in APOE2 mice but not in APOE3 or APOE4 mice. However, increased vascular inflammation was observed in both APOE2 and APOE4 mice. Single-cell RNA sequencing followed by cluster analysis identified 25 major cell types in the aorta that include various immune cell types, endothelial cells, and various vascular mural cell subsets. Results showed that cells from the APOE2 mice were enriched with genes associated with intracellular lipid accumulation and inflammation, whereas cells from the APOE4 mice displayed elevated oxidative- and/or endoplasmic reticulum-stress and inflammatory response. Thus, apoE2 accelerates atherosclerosis by inducing diet-induced hyperlipidemia and inflammation, while apoE4 does not induce hyperlipidemia but enhances inflammation that may prime the vasculature for atherosclerosis development. The distinct mechanisms by which apoE2 and apoE4 promote atherosclerosis underscore the importance of including apoE genotype information in the design of therapeutics for atherosclerosis intervention. Full article

In vitro maturation (IVM) is a critical step affecting the efficiency of bovine in vitro embryo production; however, oxidative stress during in vitro culture can impair oocyte quality and subsequent developmental competence. This study investigated the effects of cysteine supplementation on bovine oocyte IVM, redox homeostasis, mitochondrial status, and transcriptomic changes. Bovine cumulus-oocyte complexes were cultured in IVM medium supplemented with 0, 25, 50, 75, 100, or 125 μM cysteine, and 75 μM was identified as the optimal concentration. Compared with the control group, 75 μM cysteine increased the first polar body extrusion rate from approximately 78% to 81% and improved the fertilization/cleavage rate from approximately 74% to 82%. It also significantly increased the proportions of 2-cell, 4-cell, and 8-cell embryos, whereas morula and blastocyst rates were not significantly affected. At the cellular level, 75 μM cysteine significantly reduced ROS levels and increased GSH content, as indicated by changes in relative fluorescence intensity. JC-1 staining showed that the JC-1 monomer signal decreased from approximately 16.0 to 13.5, whereas the JC-1 aggregate signal increased from approximately 13.2 to 14.8, indicating improved mitochondrial membrane potential status. In addition, lipid droplet fluorescence intensity increased from approximately 11.8 to 13.4, mitochondrial fluorescence intensity increased from approximately 6.0 to 7.0, and cytoskeletal fluorescence intensity showed no significant difference between groups. Smart-seq2 transcriptomic analysis identified 1935 differentially expressed genes, including 1778 upregulated and 157 downregulated genes, which were mainly enriched in translation, ribosomal structural components, RNA binding, oxidative phosphorylation, and metabolism-related pathways. qRT-PCR further confirmed the upregulation of key genes, including NDUFS2, VDAC3, ANXA2, MTHFD1L, and SCD. Overall, 75 μM cysteine improves bovine oocyte IVM quality by enhancing antioxidant capacity, improving mitochondrial membrane potential, increasing lipid-derived energy substrate storage, and regulating genes related to energy metabolism and developmental competence. Full article

Background/Objectives: Anemia and iron dysregulation are common in chronic heart failure (CHF), but additional metabolic mechanisms may contribute to these alterations. This study aimed to evaluate purine metabolism and oxidative stress markers in patients with CHF and to explore their potential relationship with anemia. Methods: In this cross-sectional study, 176 patients with CHF and 29 control individuals were included. CHF phenotypes were classified according to left ventricular ejection fraction (HFpEF, HFmrEF, HFrEF). Purine metabolites (guanine, hypoxanthine, adenine, xanthine, and uric acid) were measured using high-performance liquid chromatography, while lipid peroxidation (LPO) and advanced oxidation protein products (AOPPs) were assessed spectrophotometrically. Non-parametric statistical tests with correction for multiple comparisons were applied. Results: Anemia was present in 40.3% of patients with CHF. Serum iron and platelet counts were significantly lower in CHF compared with controls (p = 0.001). Among purine metabolites, adenine levels were higher in CHF (nominal p = 0.009), whereas other metabolites did not differ significantly between groups. LPO levels were lower and AOPP levels were higher in CHF (p = 0.021 and p = 0.008, respectively). No statistically significant associations were observed between hemoglobin levels and purine metabolites. Conclusions: CHF is associated with alterations in iron status and oxidative stress markers, as well as changes in purine metabolism. However, no significant associations between purine metabolites and anemia were identified in this cohort, and these findings should be interpreted cautiously given the exploratory design and sample size limitations. Full article

Prostate cancer remains a major therapeutic challenge, particularly after progression to castration-resistant disease, where persistent androgen receptor signaling, metabolic adaptation, immune escape, and treatment resistance jointly limit clinical benefit. Regulated cell death (RCD) is increasingly recognized not only as an endpoint of tumor cell elimination but also as a dynamic regulator of prostate cancer progression, therapeutic vulnerability, and tumor–immune interactions. In this review, we propose an immunometabolic framework in which androgen receptor signaling, lipid and redox metabolic reprogramming, oxidative stress, and therapeutic pressure converge to shape the susceptibility of prostate cancer cells to distinct RCD modalities. We focus on autophagy and ferroptosis as two extensively studied and translationally relevant pathways, while also discussing emerging roles of necroptosis, pyroptosis, and cuproptosis. Particular attention is given to how RCD-associated signals, including damage-associated molecular patterns, inflammatory mediators, and lipid peroxidation products, may remodel the tumor immune microenvironment and influence the transition between immune-cold and immune-inflamed phenotypes. We further summarize RCD-targeted therapeutic strategies, including ferroptosis induction, autophagy inhibition, nanodrug delivery systems, rational combination therapy, and biomarker-guided patient stratification. Finally, we discuss key translational barriers, including context-dependent biological effects, limited clinical validation, tumor heterogeneity, adaptive resistance, and insufficient predictive biomarkers. By integrating cell death biology with metabolic reprogramming, immune remodeling, and therapeutic resistance, this review highlights RCD as a promising but context-dependent therapeutic vulnerability in advanced prostate cancer. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and represents a major global public health concern due to its rapidly increasing prevalence. Although current pharmacological therapies effectively achieve glycemic control, their long-term use is limited by adverse effects, high costs, patient compliance issues, and increasing interest in safer, multi-targeted therapeutic strategies. In this context, plant-derived bioactive compounds have gained attention as complementary or alternative approaches to metabolic disease management. Gymnema sylvestre (Retz.) R.Br. ex Sm (GS), traditionally known as “gurmar” (“sugar destroyer”), is one of the most extensively studied medicinal plants with significant antidiabetic potential. This review evaluates the antidiabetic effects of G. sylvestre, focusing on its phytochemical composition, molecular mechanisms, and impact on diabetes-related complications. Major bioactive constituents, including triterpenoid saponins (gymnemic acids), gurmarin-like peptides, flavonoids, and sterols, regulate glucose homeostasis, inhibit intestinal glucose absorption, preserve pancreatic β-cell function, stimulate insulin secretion, modulate lipid metabolism, and suppress inflammatory signaling pathways. Experimental and clinical evidence indicates that G. sylvestre modulates oxidative stress and inflammation associated with complications such as nephropathy, neuropathy, retinopathy, vascular dysfunction, and dyslipidemia. This review adopts a mechanism-oriented framework integrating phytochemical structure–molecular target–metabolic outcome relationships and discusses emerging strategies, including nanotechnology-based delivery systems, molecular docking, and multi-component phytotherapy. Overall, G. sylvestre represents a promising multi-target phytotherapeutic agent, highlighting directions for future mechanistic and clinical research. Full article

Bile acids are important for lipid digestion and metabolic regulation, but the roles of individual bile acids in crustaceans remain unclear. This study evaluated the effects of six dietary monomeric bile acids on growth and lipid metabolism in juvenile Pacific white shrimp. Juvenile shrimp (2.5 g) were fed a basal diet or the same diet supplemented with 0.04% bile acid (cholic acid, hyodeoxycholic acid, chenodeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, or hyocholic acid) for 8 weeks. Each treatment was assigned to three replicate 100-L tanks, with 30 shrimp per tank. Dietary monomeric bile acids did not significantly affect growth performance, body composition, or muscle fatty acid composition. Compared with the control group, chenodeoxycholic acid, deoxycholic acid, and hyocholic acid significantly reduced the hemolymph triglyceride levels, while cholic acid, chenodeoxycholic acid, and hyocholic acid lowered the hepatopancreatic lipid levels. All bile acid treatments reduced the hepatopancreatic malondialdehyde content compared with the control group. Expression of genes related to bile acid transport, sterol metabolism, and lipid catabolism was generally upregulated by bile acids, indicating enhanced bile acid circulation and lipid turnover. In conclusion, monomeric bile acids mainly regulate lipid metabolism and oxidative status rather than directly promoting growth under the present dietary condition, with chenodeoxycholic acid, cholic acid, and deoxycholic acid showing relatively stronger effects. Full article

This study evaluated the effects of monolaurin intake per finishing feedlot cattle on growth performance, metabolic status, ruminal environment, and meat fatty acid profile. Twenty-four castrated Holstein males (379 ± 8.5 kg; 12 months old) were randomly assigned to two treatments: basal diet (control) or basal diet with α-monolaurin (treated: 0.762 g/kg dry matter intake; ≈6.63 g/animal/day) for 79 days. Feed intake, body weight, and feed efficiency were recorded, and blood and ruminal samples were collected during the trial. Ruminal fermentation parameters, protozoa counts, hematological and biochemical variables, oxidative status biomarkers, ruminal microbiota composition (16S rRNA sequencing), and Longissimus dorsi fatty acid profile were analyzed. Monolaurin feed did not affect dry matter intake or final body weight, but increased total weight gain, average daily gain, and feed efficiency (p ≤ 0.05), indicating improved nutrient utilization. Hematological and serum biochemical variables were largely unchanged, although total leukocyte counts were lower in treated cattle. Animals receiving monolaurin showed reduced reactive oxygen species and lower superoxide dismutase activity, suggesting improved oxidative balance without changes in lipid peroxidation. During the adaptation phase (day 14), treated cattle exhibited lower acetate, propionate, valerate, and total volatile fatty acid concentrations and higher protozoa counts, but these differences disappeared by day 79, indicating ruminal adaptation. Microbiota diversity was not altered overall, although specific genera differed in relative abundance between treatments. In meat, monolaurin increased lauric, linoleic, and arachidonic acids, reduced palmitic and heptadecanoic acids, decreased total saturated fatty acids, and increased polyunsaturated fatty acids (p ≤ 0.05). Overall, dietary monolaurin improved feed efficiency, modulated oxidative status, induced transient ruminal microbial adjustments, and enhanced the nutritional quality of beef lipids without compromising metabolic health. Full article

Environmental exposure to persistent and non-persistent endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), dioxins, phthalates, and bisphenols, has been increasingly associated with elevated cardiovascular disease (CVD) risk. Emerging evidence suggests the importance of gene–environment interactions in modulating individual susceptibility to EDC-related cardiovascular effects. This review summarizes current knowledge by synthesizing the main classes of EDCs, evaluating the evidence linking them to cardiovascular outcomes, and highlighting how genetic variability may modulate EDC-induced cardiovascular risk. Across the studies analyzed, the most extensively investigated genetic polymorphisms involve pathways related to oxidative stress regulation, xenobiotic metabolism and detoxification, hormone signaling, and lipid homeostasis. Variants in antioxidant defense genes, such as CAT, eNOS, and PON1, have been associated with increased hypertension risk and vascular dysfunction following exposure to bisphenols and PAHs. Polymorphisms in GSTP1, CYP2C19, CYP1A2, CYP2E1, ABCB1, and MTHFR may influence susceptibility to cardiometabolic alterations and congenital heart defects, whereas variants in ESR2, FTO, LEPR, and INSIG2 have been linked to obesity, dyslipidemia, and hypertension associated with PFAS, PBDEs, and bisphenols. A deeper understanding of gene–environment interactions is essential to advance preventive cardiology and mitigate the cardiovascular impact of environmental pollutants. Full article

The prevention and treatment of cardiovascular disease (CVD) are undergoing a paradigm shift from a lipid-centric approach to a holistic metabolic perspective. Central to this evolution is the gut–fat–heart axis, a sophisticated three-dimensional communication network that integrates neural, endocrine, and immunometabolic signaling to regulate systemic lipid homeostasis. This manuscript systematically explores how the gut microbiota acts as a “metabolic organ” to remotely control host health through the production of bioactive metabolites and the modulation of molecular communication networks. At the physiological level, microbial products such as short-chain fatty acids (SCFAs) and modified bile acids regulate energy balance and lipid synthesis via the FXR-FGF15/19 axis and G protein-coupled receptors. Furthermore, gut hormones like GLP-1 and neuro-reflex pathways involving the vagus nerve provide rapid control over postprandial lipid clearance and feeding behavior. Conversely, pathological dysbiosis triggers the accumulation of harmful metabolites, such as trimethylamine N-oxide (TMAO) and lipopolysaccharides (LPS), which drive lipotoxicity, vascular inflammation, and “dysfunctional HDL” formation. These processes accelerate the progression of atherosclerosis, heart failure, and metabolic syndrome. Finally, the article outlines promising clinical translation strategies, including the development of TMA lyase inhibitors, next-generation probiotics, and the use of phytochemicals to reshape the microbial landscape. By decoding the molecular dialogues within the gut–fat–heart axis, this research provides a novel strategic vantage point for the integrated management of cardiovascular–kidney–metabolic (CKM) syndrome. Full article

Aquatic organisms are exposed to multiple stressors, including microplastic pollution and rising temperatures. Bioplastics like Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are considered sustainable alternatives to conventional plastics, although their biological effects remain poorly understood. This study evaluated the effects of PHBV microplastics on Artemia franciscana under different temperature and exposure conditions. Organisms were exposed to 25 and 100 mg·L⁻¹ PHBV for 7, 14, and 21 days at 25 °C and for 14 days at 29 °C. Growth, development, antioxidant enzyme (CAT, GST) and esterase activities (ChE, CbE), lipid peroxidation (LPO), gut histology, fatty acid profiles and polymer particle length distributions were assessed. Growth and development increased with PHBV concentration, exposure time, and temperature. Enzymatic activities and LPO were significantly affected by these factors, although no evidence of oxidative damage was detected. Marked gut lesions were observed at 100 mg·L⁻¹ PHBV at 29 °C after 14 days. Fatty acid profiles were mainly influenced by time and temperature, while high PHBV levels were associated with additional, more subtle changes in long-chain polyunsaturated fatty acids. PHBV particle length distributions also varied depending on exposure conditions. These findings suggest that PHBV induces physiological responses distinct from those typically reported for conventional microplastics and highlight the importance of considering multiple stressors in ecotoxicological studies. Full article

Background/Objectives: Diabetic cardiomyopathy (DCM) is largely driven by severe oxidative stress and calcium dyshomeostasis. We examined the targeted antioxidant and therapeutic effects of zinc sulfate (ZnSO₄) on contractile dynamics, oxidative damage, calcium turnover, and apoptosis/fibrosis in aged female rats with type 2 diabetes. Methods: Thirty-two aged female Wistar rats were divided into Control, Control + ZnSO₄, Diabetes (DM), and DM + ZnSO₄ groups. DM was induced via high-fat diet and 30 mg/kg streptozotocin. After a 4-week complication period, treatment groups received 10 mg/kg/day ZnSO₄ (i.p.) for 6 weeks. Left ventricular papillary muscle contraction, oxidative/antioxidant markers (MDA/GSH), and gene expressions (SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, PLN) were evaluated. Myocardial architecture, fibrosis, and apoptosis were analyzed immunohistochemically. In DM rats, contractile force (CF) and velocities (±dF/dtmax) significantly declined. Results: Concurrently, SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, and antioxidant GSH decreased, while oxidative lipid damage (MDA), PLN, Caspase-3 activity, Collagen I, and fibrosis increased (p < 0.001). ZnSO₄ treatment in diabetic rats acted as a potent antioxidant modulator; it restored redox balance, activated the SIRT1/GLUT4 pathway, protected calcium-handling proteins from oxidative degradation, and significantly improved contractile dynamics. It also preserved myocardial architecture by reducing apoptosis and fibrosis. In healthy rats, ZnSO₄ caused mild stress and early fibrosis. Conclusions: In conclusion, while inducing mild stress in healthy myocardium, zinc supplementation provides robust antioxidant protection in diabetic hearts. It activates SIRT1, suppresses oxidative damage, maintains calcium homeostasis, and restores contractile dynamics, demonstrating strong antioxidant therapeutic potential against DCM. Full article