Search Results (3,158)

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

Iron overload disrupts cellular homeostasis and drives ferroptosis through dysregulated iron metabolism. Non-coding RNAs (ncRNAs) are considered as key regulators of various biological functions and targets for a new generation of RNA therapeutics and biomarkers. However, few studies have investigated the regulatory roles of ncRNAs, particularly competitive endogenous RNAs (ceRNAs) in iron overload. This study performed whole-transcriptome sequencing to characterize the ceRNA network in ferric ammonium citrate (FAC)-induced iron-overloaded HT-1080 fibrosarcoma cells. A total of 208 differentially expressed mRNAs, 83 lncRNAs, and 170 circRNAs (q < 0.05) were identified, with hierarchical clustering revealing distinct expression patterns between control and iron-treated groups. KEGG enrichment implicated vitamin B6 metabolism (q < 0.001) and lysine degradation (q < 0.001) as key disrupted pathways. ceRNA network was conducted and further demonstrated lncRNA/circRNA-mediated regulation of ferroptosis genes via shared miRNA response elements. Notably, LINC-PINT-232 was implicated in the regulation of both ferritin heavy chain (FTH) and sequestosome 1 (SQSTM1), two ferroptosis-associated mRNAs. FTH upregulation mitigates iron toxicity through ferroxidase activity, while SQSTM1 modulates lipid peroxidation in ferroptosis. These findings provide a preliminary transcriptomic landscape for hypothesis generation regarding ncRNA-mediated regulatory mechanisms in iron overload-induced ferroptosis and offer a computational foundation for future functional and therapeutic investigations. 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

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

Background/Objectives: Red beetroot (Beta vulgaris L.) is recognized for its antioxidant, anti-inflammatory, and metabolic properties. This study evaluated the effects of two beetroot cultivars (Boldor and Wodan) on blood serum parameters, body composition, and organ weights in male WKY rats fed a low-protein diet (LPD, 8.8% protein). Methods: Five-week-old male rats were maintained on an LPD for 8 weeks and subsequently continued on the LPD diet supplemented with 4% dried beetroot for 45 days. The experimental diets included beetroot from the Boldor and Wodan cultivars, either treated or untreated with a plant growth stimulator during cultivation. Results: Foliar application of the selenium-based plant growth stimulator did not significantly increase selenium or other element concentrations in beet roots. Elemental analysis showed higher levels of Fe, Zn, Cu, Cr, Pb, As, Cd, and Sb in the Wodan group, while Boldor increased Cr, Pb, and As; Ni and Se remained unchanged. Beetroot supplementation significantly affected 14 of the 30 measured biochemical parameters, including biomarkers of liver function (ALT, ALP, total bilirubin, albumin, and total protein), renal function (uric acid), pancreatic activity (amylase and lipase), electrolyte balance (sodium, potassium, and chloride), mineral metabolism (calcium), inflammatory status (CRP), and nutritional metabolism (iron). Conversely, no significant effects were observed on lipid profile parameters or biomarkers of cardiac and skeletal muscle injury. Among the beetroot cultivars evaluated, Wodan exerted distinct effects relative to Boldor, resulting in higher circulating total bilirubin and potassium concentrations, alongside reduced uric acid and lipase levels in treated rats. Boldor supplementation significantly increased body weight gain and fat mass, with a trend toward higher lean mass, and increased kidney weight. Wodan did not significantly affect body weight but increased kidney and spleen mass. Feed intake was similar across groups. No changes in cardiovascular function were observed ex vivo. Conclusions: Beetroot supplementation modulated multiple metabolic and physiological biomarkers in rats fed a low-protein diet, with distinct cultivar-specific effects, underscoring the importance of cultivar selection for optimizing functional dietary interventions. Full article

The mammalian brain fundamentally relies on precise lipid homeostasis to maintain structural integrity and complex neural signaling. Emerging evidence positions lipid metabolism reprogramming not merely as a secondary pathological byproduct but as a core initiating driver of age-related neurodegenerative diseases. This review systematically evaluates the mechanisms of cerebral lipid dyshomeostasis during brain aging, highlighting glial cells as the central mediators of this pathological cascade. We comprehensively dissect the age-associated “lipid drift”, emphasizing apolipoprotein E (APOE)-induced cholesterol transport defects and lipid raft pathology, the accumulation of lipid droplets that triggers microglial metabolic stress (LDAMs), and ceramide-driven neuronal apoptosis coupled with the exosome-mediated propagation of pathogenic proteins. Furthermore, we map these aberrant lipid networks to specific pathological signatures in Alzheimer's, Parkinson's, and demyelinating diseases. Finally, we critically evaluate promising therapeutic interventions, including nutritional strategies, LXR/RXR agonists, and nanotechnology-enabled delivery systems designed to bypass the blood–brain barrier. By integrating high-throughput lipidomics for early diagnostic biomarker discovery, we underscore the translational imperative of restoring cerebral lipid homeostasis as a disease-modifying strategy for neurodegeneration. Full article

Watercress (Nasturtium officinale R.Br.) is a cruciferous vegetable rich in bioactive compounds that may improve cardiovascular disease (CVD) risk factors. However, clinical evidence regarding its direct impact on CVD risk remains limited. This study evaluated the efficacy of watercress consumption on cardiovascular parameters, oxidative stress biomarkers, and estimated CVD risk in middle-aged Thai adults with low-to-moderate risk. Twenty-five participants completed the randomized, placebo-controlled pilot study. The watercress group (n = 12) consumed 16 dried watercress capsules daily for four weeks, while the placebo group (n = 13) received a placebo. Physical examinations, arterial stiffness, lipid profiles, and biochemical biomarkers were analyzed at baseline and the end of treatment. The 10-year CVD risk was estimated using the Framingham equation. Following the intervention, the watercress group showed significant reductions in both systolic and diastolic blood pressure compared to the placebo group. Within the watercress group, significant improvements from baseline to post-intervention were observed in oxidized LDL, antioxidant capacity (ABTS), and estimated 10-year CVD risk score. However, these three parameters did not reach statistical significance when compared to the placebo group. In conclusion, daily watercress consumption significantly lowers blood pressure and demonstrates a potential dietary option for supporting cardiovascular health. Nevertheless, larger and longer-term clinical trials remain necessary. Full article

Background/Objectives: Sarcopenic obesity (SO) represents a severe clinical phenotype characterized by the coexistence of reduced skeletal muscle mass and excess adiposity, and is associated with insulin resistance, dyslipidemia, and systemic inflammation. However, easily accessible biomarkers that capture early molecular changes underlying SO are lacking. The aim of this pilot study was to compare circulating microRNA (miRNA) profiles in patients with severe obesity and a sarcopenic obesity phenotype with those of healthy controls and to identify candidate miRNAs suitable for further validation. To the best of our knowledge, this represents one of the first broad screening studies of circulating miRNAs specifically conducted in patients with severe obesity and DXA-confirmed sarcopenic obesity. Methods: In this single-center pilot study conducted in the Czech Republic, fasting plasma samples from 12 adult participants (6 with severe obesity and sarcopenic obesity phenotype, body mass index > 45 kg/m²; 6 healthy controls; age 18–65 years) were analyzed using an RT-qPCR panel comprising 384 assays, including technical controls and 352 target circulating miRNAs. Following predefined quality control and filtering criteria, 224 miRNAs were retained for the final statistical analysis. Six patients with severe obesity were classified according to the ESPEN/EASO 2022 consensus criteria for sarcopenic obesity, while EWGSOP2-based assessment was used for functional evaluation of sarcopenia. Differential expression was evaluated using fold change and exploratory statistical testing. Results: We identified a set of miRNAs with significantly altered expression in SO, including increased muscle-enriched miR-486-5p and hepatocyte-enriched miR-122-5p, and decreased vascular miR-145-5p, as well as several additional miRNAs related to myogenesis, lipid metabolism and inflammatory signaling. miR-451a, a recognized marker of hemolysis, was also increased but was interpreted with caution. Conclusions: Despite the limited sample size, the results of this study suggest that specific circulating miRNAs may reflect key pathophysiological pathways in SO and could serve as promising biomarkers to support risk stratification and monitoring in larger, hypothesis-driven studies. Full article

Gestational diabetes mellitus (GDM), as one of the most common metabolic disorders occurring during pregnancy, represents a significant public health concern due to its rising prevalence and the numerous complications that can affect both the mother and the foetus. In recent years, there has been growing interest in the use of omics technologies, such as metabolomics and proteomics, in research on the pathogenesis and early detection of GDM. The aim of this paper was to summarise the current knowledge on metabolomic and proteomic changes observed in women with GDM and to assess the potential usefulness of these methods in identifying biomarkers of the disease. The narrative review was conducted in accordance with the PRISMA 2020 statement, using PubMed and Web of Science until 23 December 2025. The studies analysed show that GDM is associated with abnormalities in the metabolism of lipids, amino acids, carbohydrates and metabolites associated with the gut microbiota. The most commonly observed changes included: elevated levels of branched-chain amino acids, free fatty acids and purine metabolites, as well as changes in the metabolism of phospholipids and acylcarnitines. Multi-omics studies also indicate significant changes in plasma protein and lipid profiles. The data collected suggest that omics technologies may be a promising tool for identifying early biomarkers of GDM and for developing our understanding of the pathophysiological mechanisms of this condition. Nevertheless, further studies involving larger and more diverse patient populations are needed to confirm their diagnostic and clinical value. Full article

Background: The increasing prevalence of overweight and obesity highlights the need for practical and sustainable dietary strategies for weight management. Although dietary fibre intake is associated with improved satiety and metabolic health, achieving recommended intake levels through whole foods alone remains challenging. Evidence supporting convenient, ready-to-consume fibre beverages in free-living overweight adults is also limited. Therefore, this study evaluated the effects of a soya-based dietary fibre beverage (SBB) on body composition and metabolic parameters in overweight adults. Methods: A 12-week parallel, cluster-randomized controlled trial was conducted on overweight university students and staff. An intervention group (IG) (n = 21) consumed the soya-based dietary fibre twice daily for 12 weeks, while the control group (CG) (n = 21) continued their habitual diet. Results: Significant group × time interactions were observed for body weight (p < 0.001), BMI (p = 0.021), waist circumference (p = 0.046), waist-to-hip ratio (p = 0.042), and body fat percentage (p = 0.004). The IG showed reductions in body weight (−1.12 kg), waist circumference (−4.29 cm), and body fat percentage (−0.73%), whereas the CG demonstrated minimal changes. No significant changes were observed in fasting glucose, lipid profile, CRP, or IL-6, suggesting no clinically significant adverse biochemical changes during the intervention period and supporting its short-term tolerability. Dietary analysis confirmed a marked increase in fibre intake in the IG (~50 g/day), indicating good adherence to the intervention. Conclusions: SBB supplementation improved body composition and central adiposity without affecting systemic inflammatory biomarkers and may represent a practical dietary approach for weight management in free-living overweight adults. Further studies are needed to confirm its long-term efficacy and safety. Full article

Background/Objectives: Elevated homocysteine (Hcy) levels are associated with endothelial dysfunction, oxidative stress, and inflammation, contributing to cardiovascular disease development. The aim of this study was to examine the effects of vitamin B6 and folic acid on cardiometabolic biomarkers, cardiac oxidative stress, metabolic enzyme activities and cardiovascular histomorphometric parameters in homocysteine-loaded rats. Methods: Male Wistar albino rats were divided into four groups (n = 10, per group): C—saline 0.2 mL/day s.c. + saline 0.5 mL i.p; H: Hcy 0.45 µmol/g b.w./day s.c. + saline 0.5 mL i.p; C-B6+FA—saline 0.2 mL/day s.c. + vitamin B6 (7 mg/kg b.w. i.p./day) and folic acid (FA) (5 mg/kg b.w. i.p./day); and H-B6+FA—Hcy (0.45 µmol/g b.w./day s.c.) + vitamin B6 (7 mg/kg b.w. i.p./day) and FA (5 mg/kg b.w. i.p./day). Substances were applied s.c. for 2 weeks and i.p for 4 weeks. Results: B6+FA supplementation significantly reduced serum Hcy and LDL concentrations and attenuated Hcy-associated increases in cardiac SOD activity and right ventricular wall thickness. However, B6+FA was associated with increased cardiac MDA levels. MDH activity increased mainly in non-Hcy-loaded supplemented rats, whereas LDH activity, the cardio-somatic index, and aortic histomorphometric parameters remained unchanged. Conclusions: Combined B6+FA supplementation may improve Hcy metabolism, the LDL profile, and selected cardiac structural/oxidative alterations, but its association with increased lipid peroxidation suggests complex redox effects requiring cautious interpretation. Full article

Atherosclerosis is a progressive vascular disease characterized by lipid-rich plaque accumulation, oxidative stress, and chronic inflammation, contributing to coronary heart disease, stroke, and peripheral arterial disease. This study investigated the impact of inflammation, vascular calcification, and statin therapy on redox balance in blood and carotid artery plaques, aiming to identify potential biomarkers for disease assessment. Thirty-two patients undergoing carotid endarterectomy provided 34 plaque samples. Enzyme activities in plaque/erythrocytes and –SH group concentration in plasma/plaque were measured. Pathological analysis was performed to determine inflammation/calcification grade, the presence of mast cells and plaque composition. The results showed that mast cells were associated with reduced non-protein –SH groups, indicating selective thiol consumption and serving as a qualitative marker of oxidative burden. Reduced catalase activity in erythrocytes was associated with advanced calcification, pointing to long-standing systemic oxidative stress. Statin therapy enhanced systemic superoxide-dismutase 1 activity, increased –SH groups, and modulated plaque-specific glutathione reductase activity, attenuating sex-related differences in redox regulation. These findings highlight the complex interplay between systemic and local oxidative processes in atherosclerosis through alterations in redox-related biomarkers such as plasma –SH group concentrations and catalase activity. Full article

Oxidative stress biomarkers are elevated in liver cirrhosis, but their clinical utility for severity staging and complication prediction remains uncertain. This retrospective single-centre study enrolled 90 patients with decompensated cirrhosis (Child–Pugh classes B and C) to evaluate serum malondialdehyde (MDA) and 8-isoprostane (8-isoPGF2α) as predictors of Child–Pugh severity, severe ascites, and severe hepatic encephalopathy, and to quantify their incremental value within supervised machine learning models. Four algorithms—logistic regression, Random Forest, Gradient Boosting, and Support Vector Machine—were evaluated using stratified 10-fold cross-validation; logistic regression models with and without oxidative stress biomarkers were compared for the prediction of ascites and encephalopathy. Routine biochemical parameters effectively discriminated Child–Pugh class B from C, with machine learning models achieving AUC-ROC values of 0.921–0.972. Neither MDA nor 8-isoPGF2α differed between Child–Pugh classes or across ascites categories, and both failed to improve ascites prediction (ΔAUC = −0.015). For severe hepatic encephalopathy, the extended model showed modest but consistent improvements in accuracy (+3.4 percentage points), sensitivity (+6.4%), and model fit, suggesting an outcome-specific complementary role consistent with the established involvement of lipid peroxidation in ammonia neurotoxicity. These findings support the use of machine learning for automated cirrhosis severity classification and indicate that oxidative stress biomarkers hold selective relevance for hepatic encephalopathy rather than global disease staging. Full article

Metabolically dysfunction-associated steatotic liver disease (MASLD) complicated by type 2 diabetes mellitus (T2DM) represents a clinically aggressive phenotype associated with accelerated hepatic fibrosis progression. The interplay among oxidative stress, systemic inflammation, and the risk of hepatic fibrosis in this context remains incompletely characterised. We conducted a single-centre observational study enrolling 110 adult MASLD patients, stratified into two groups: Group 1 (G1, n = 20), patients with concurrent T2DM, followed longitudinally at three successive time points, and Group 2 (G2, n = 90), non-diabetic controls. Serum oxidative stress biomarkers were assessed using malondialdehyde (MDA) and 8-isoprostaglandin F2α (8-iso-PGF2α). Systemic inflammatory status was quantified through the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR). Hepatic fibrosis risk was estimated using the FIB-4 index. Diabetic MASLD patients exhibited significantly elevated levels of 8-iso-PGF2α (p = 0.014) and NLR (p = 0.016) compared with controls, indicating greater oxidative membrane damage and systemic neutrophilic inflammation. A robust inverse correlation between PLR and FIB-4 was observed across all analytical strata (combined cohort: Spearman r = −0.680, p < 0.001). MLR emerged as the only independent predictor of MDA in G1 (β = 841.78, p = 0.013). Longitudinal analysis demonstrated biomarker stability over time, except for a significant increase in ALT from T1 to T2 (p_adj = 0.014). These findings support the clinical utility of routinely available haematological inflammatory ratios and lipid peroxidation biomarkers for phenotypic characterisation of MASLD in the diabetic context, highlighting the need for larger prospective studies with histological validation. Full article

Atherosclerosis (AS) is the primary underlying cause of cardiovascular and cerebrovascular diseases. The occurrence and development of AS are closely related to lipid deposition, chronic inflammation, phenotypic modulation of vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM) remodeling. Numerous studies indicate that low-density lipoprotein receptor-associated protein 1 (LRP1), as a multifunctional receptor, contributes to vascular homeostasis in AS and vascular remodeling by regulating lipid handling, inflammatory responses, transforming growth factor beta (TGFβ) signaling, and platelet-derived growth factor receptor beta (PDGFRβ) trafficking. Rather than treating the LRP1-TGFβ-PDGFRβ relationship as a fully established linear pathway, this review distinguishes demonstrated mechanisms from inferred cross-talk and proposes an integrated, cell- and stage-dependent regulatory model. This article systematically elaborates on the structure and function of LRP1; LRP1-mediated regulation of TGFβ and PDGFRβ in AS and vascular remodeling; the possible relationship among LRP1, TGFβ, and PDGFRβ; and cell-specific effects in VSMCs, macrophages, endothelial cells, and pericytes. Meanwhile, this article summarizes potential translational strategies such as lipid-lowering, anti-inflammatory therapy, PDGFRβ inhibitor repositioning, TGFβ pathway modulation, biomarker-based stratification, and LRP1-targeted delivery. A deeper understanding of the cell-specificity and stage-dependence of the LRP1-TGFβ-PDGFRβ signaling network may help elucidate the progression mechanism of AS and provide new ideas for risk stratification and precise intervention. Full article