We evaluated the efficiency of two-dimensional (2D) and three-dimensional (3D) systems for in vitro culture of preantral follicles from the bovine species. Ovarian cortex fragments were obtained from a local slaughterhouse and randomly distributed into four groups: i) standard culture, directly on a culture plate (2D), ii) supported culture, on a gel monolayer (2D), iii) immersed culture on agarose gel (plating coated) covered in a medium (3D) and iv) Millicell–Biopore culture (3D), tested at 6 or 14 days. The following parameters were evaluated: follicular morphology and morphometry, reactive oxygen species production and granulosa cell proliferation. After 6 days of culture, follicles cultured on a gel monolayer (2D) showed a higher proportion of intact follicles than those cultured using other methods (P < 0.05). After 14 days of growth, standard culture on a culture plate (2D) and supported culture on a gel monolayer (2D) had a higher percentage of morphologically intact follicles (P < 0.05) than the 3D culture. An assessment of the redox status revealed that superoxide anion levels and antioxidant capacity of the samples cultured using the four methods were lower than those of the control group (non-cultured; P < 0.05). Taken together, these findings suggest that the agarose gel support system offers distinct advantages for bovine preantral follicle culture by maintaining morphological integrity and stabilising the redox environment, although further studies incorporating functional endpoints are warranted to fully confirm these observations.

Women with diabetes frequently experience ovarian dysfunction, which is a significant indication that diabetes adversely affects their reproductive health. This study investigates the efficacy of combined treatment with Pioglitazone and Cynara scolymus extract in improving ovarian function in streptozotocin-induced diabetic rats. A total of 35 female rats were divided into five groups: (1) Control (saline), (2) DM (diabetic control), (3) DM + Piog (30 mg/kg Pioglitazone), (4) DM + Cynara (400 mg/kg C. scolymus extract), and (5) DM + Piog + Cynara (combined treatment), and were administered orally for 30 consecutive days. Following treatment, histopathological and stereological analyses were performed to evaluate follicular development, corpus luteum volume, and oxidative stress markers. The results indicated that the combined treatment (DM + Piog + Cynara) led to significant improvements, including increased numbers of preantral, antral, and Graafian follicles, alongside an enhanced corpus luteum volume. Additionally, there was a notable reduction in atretic follicles and fasting blood glucose levels compared to the diabetic group. Diabetes resulted in elevated malondialdehyde (MDA) levels and decreased antioxidant enzyme activities. However, the combination therapy effectively modulated apoptotic pathways, enhancing Bcl-2 expression while reducing Caspase-9 activity. This study demonstrates that the combined therapy of C. scolymus extract and Pioglitazone mitigates diabetic-induced ovarian dysfunction by reducing oxidative stress, normalizing hormonal levels, and promoting healthy folliculogenesis. These findings suggest that this approach may serve as a promising complementary treatment for diabetes-related reproductive issues, potentially improving reproductive health.

Hysterothylacium thalassini third-stage larvae (L3), commonly found in marine fish, are known to induce liver injury, oxidative stress, and immune disturbances when transmitted to mammalian hosts. This study investigated the pathological effects of purified crude extracts derived from fresh, heat-treated, and frozen L3 larvae on liver function, oxidative status, and immune responses in a murine model. Thirty Saurida tumbil fish were examined for L3 larvae, which were processed under three conditions: fresh (24 ± 2 °C for 60 min), heat-treated (100 °C for 60 min), and frozen (−20 °C for 24 h). Twenty male C57BL/6 mice were randomly allocated into four groups and inoculated with larval extracts at a 14-day interval. Mice exposed to fresh larval extracts exhibited significant weight loss, elevated liver enzymes (ALT, AST, ALP), hyperglycemia, and reduced total protein levels, alongside severe hepatic damage characterized by necrosis and inflammatory infiltration. Antioxidant enzyme activities (CAT and SOD) were markedly decreased, whereas oxidative stress markers (NO and H₂O₂) were increased. Additionally, there was significant upregulation of iNOS, TNF-α, and IL-10 gene expression, accompanied by elevated iNOS, IL-10, and IgE protein levels, indicating strong inflammatory and Th2-type immune responses. In contrast, extracts from heat-treated and frozen larvae resulted in attenuated pathological effects, including improved liver function, reduced oxidative stress, and moderated immune responses. These findings demonstrate that untreated L3 larval extracts exert pronounced hepatotoxic and immunomodulatory effects, while thermal and freezing treatments significantly reduce their pathogenicity and support immune homeostasis, highlighting potential strategies to mitigate parasite-induced host damage.

Malathion is an insecticide widely used in agriculture and, in Brazil, was heavily applied in the 2010s to control Aedes mosquitoes. Its use exposes the general population, including children and adolescents, to this pesticide. As puberty reflects the maturing of the reproductive system, this study investigated whether preconception exposure to low doses of malathion during juvenile and pubertal stages affects fertility and pregnancy outcomes in Wistar rats. Female rats received daily gavage doses of 10 or 50 mg/kg from postnatal day (PND) 22 to 60. Puberty onset was monitored starting on PND 27. Following exposure, females were mated at the first proestrus and euthanized on gestational day (GD) 18. Malathion advanced puberty onset (M50) but did not impair fertility or serum hormonal levels. Females exposed to the higher dose showed increased urea levels. Additionally, placental integrity was compromised, with reduced placental glycogen (M10) and increased oxidative stress and reduced offspring CRL. These findings indicate that preconception exposure to low doses of malathion negatively impacted placentation and offspring’s intrauterine development at GD 18.

Jaboticaba, Plinia cauliflora [Mart.] Kausel (Myrtaceae) is a native Brazilian fruit high in bioactive compounds with potent antioxidant and anti-inflammatory properties. We present the first protocol (randomised crossover with a washout period) for a clinical trial investigating the effects of consuming jaboticaba peel extract on inflammation, oxidative stress and gut dysbiosis in patients with chronic kidney disease (CKD) undergoing haemodialysis. Thirty eligible patients will be randomly assigned to the intervention group (3·3 g/d of jaboticaba peel extract, providing 650 mg/d of phenolic compounds) or to the placebo group (corn starch). The total daily dose will be administered as four capsules, divided into two doses per day, for 2 months. Following the washout period (2 months), patients will continue the supplementation in a crossover design for the same duration. Blood and fecal samples, food intake data and anthropometric measurements will be evaluated. Inflammatory markers and antioxidant enzymes will be assessed using real-time protein chain reaction, cytokine plasma levels will be measured by Luminex, and uremic toxin plasma levels will be analysed using high-performance LC. The fecal microbiome will be evaluated through high-throughput sequencing of the 16S rRNA gene amplicons. Conducting a rigorously designed trial using jaboticaba will provide essential information and generate new evidence to support nutritional strategies that utilise typical Brazilian fruits for patients with CKD.

Smoking has been confirmed to induce systemic inflammation and oxidative stress (OS) and is associated with higher odds of chronic obstructive pulmonary disease (COPD). Dietary antioxidants can reduce inflammation and OS. This study seeks to score the dietary antioxidant intake and then assess its impact on the association between smoking and COPD in adults. The data extracted from the 2007–2012 National Health and Nutrition Examination Survey database were used. The Dietary Antioxidant Quality Score (DAQS) was evaluated by the total intake of vitamins A, C and E, Se, Zn and Mg in the daily diet. Smoking was used as the exposure variable and COPD as the outcome variable. Weighted multivariable logistic regression was conducted to evaluate the associations of DAQS with smoking and COPD, as well as their joint effects on the odds of COPD. The relationships between dietary antioxidant quality score, smoking status and COPD were subsequently assessed. Subgroup analyses were performed to explore associations between relevant covariates and smoking and COPD across DAQS strata. Current smoking was found to be linked to COPD (OR = 4·06, 95 % CI = 3·14, 5·27) in comparison to never smoking. Among smokers, significant associations were observed in both the medium-quality DAQS group (OR = 3·48, 95 % CI: 2·34, 5·17) and the low-quality DAQS group (OR = 5·60, 95 % CI: 3·58, 8·76). In conclusion, high DAQS levels are inversely related to the odds of COPD in adult smokers. Our findings provide valuable insights for management strategies for COPD.

Oxeiptosis is a reactive oxygen species (ROS)-dependent form of programmed cell death that plays a key role in cellular homeostasis and holds promise as a cancer therapy. This review explores its molecular mechanisms, emphasizing the KEAP1–PGAM5–AIFM1 signalling pathway and its reliance on ROS accumulation. Compared to other cell death pathways, oxeiptosis offers a distinct approach, especially for targeting cancer cells resistant to conventional therapies. The review evaluates emerging inducers, both synthetic and natural, that selectively trigger oxeiptosis in cancer cells. It also examines the potential synergy between oxeiptosis and ROS-generating chemotherapies, particularly in the oxidative tumour microenvironment. However, challenges remain, including identifying tumour-specific inducers, overcoming cancer cell resistance to oxidative stress and reducing off-target effects. The review concludes by highlighting the need for targeted delivery strategies and rigorous preclinical studies to translate oxeiptosis into effective cancer treatments. Overall, it underscores oxeiptosis as a promising avenue to address drug resistance and improve therapeutic outcomes in oncology.

The purpose of this systematic review and meta-analysis was to investigate the effects of hesperidin supplementation on inflammatory and oxidative stress biomarkers in human adults. A systematic literature search was conducted in PubMed, EMBASE and Cochrane Central Register of Controlled Trials from inception to 4 January 2025 to identify eligible randomised controlled trials. Ten randomised controlled trials with a total of 532 participants were included. The results indicated that hesperidin supplementation significantly reduced the serum levels of C-reactive protein or high-sensitivity C-reactive protein (SMD: –0·43; 95 % CI –0·71, –0·15; P = 0·002) and TNF-α (SMD: –0·51; 95 % CI –0·95, –0·07; P = 0·02) in adults, while no significant beneficial effect of hesperidin on IL-6 was observed (SMD: –0·25; 95 % CI –0·52, 0·01; P = 0·06). In addition, hesperidin intake showed a beneficial impact on the IL-6 level in patients with diseases (type 2 diabetes and myocardial infarction) (SMD: –0·38; 95 % CI –0·72, –0·04; P = 0·03) yet not in healthy adults without diagnosed diseases. Our findings demonstrated that hesperidin supplementation could lower the serum levels of C-reactive protein or high-sensitivity C-reactive protein and TNF-α in adults.

Maternal nutrition is critical for foetal brain development, and dietary polyphenolic compounds play an important role in mitigating oxidative stress, inflammation, and neurotoxic damage. This narrative review explored the potential promotion of brain development by polyphenols such as resveratrol, curcumin, quercetin, naringin, ferulic acid, genistein, and fisetin through their antioxidant, anti-inflammatory, and neurotrophic effects. The key molecular mechanisms are central to the advantageous actions of these polyphenols in the neurogenesis process. These compounds protect against neurodevelopmental challenges induced by maternal high-fat diet, immune activation, environmental toxins, and psychological stressors. However, their efficacy may depend on dosage, timing of administration, and maternal-foetal metabolic interactions, emphasising the need for personalised maternal nutrition strategies. Further research is needed to investigate the long-term effects and interactions of these compounds with other nutrients toward personalised maternal nutrition strategies. This narrative review presents the potential of polyphenols to support foetal brain health with an emphasis on their possible incorporation into maternal dietary interventions.

Chrysobalanus icaco L. (Caco) is a fruit tree distributed in tropical areas of Africa and America. Its seeds are a rich source of bioactive compounds, and their consumption could have a positive impact on human health during dyslipidaemias. The objective of this study was to evaluate the hypolipidaemic and antioxidant activities of aqueous extract of Caco seeds in an in vivo model of hypertriglyceridaemia induced by Triton WR-1339 (tyloxapol). Phytochemical characterisation revealed saponin and phytic acid contents of 4730 ± 190 µg of saponin equivalents and 1·0 ± 0·05 µg phytic acid equivalents g–1 of sample, respectively. Phenolic acids and flavonoids (ellagic acid, apigenin-7-O-glucuronide and myricetin, among others) were identified by HPLC-quadrupole time-of-flight (TOF) -MS. Aqueous extract of Caco seeds was administered once daily for three consecutive days at two doses (150 and 600 mg/kg) in male CD1 mice, where treatment with 600 mg/kg reduced serum TAG levels by 64 % compared with control, decreased oxidative damage to lipids and proteins and modulated superoxide dismutase and glutathione peroxidase activity in hepatic tissue. Complementary in silico molecular docking analyses suggested a potential interaction of apigenin-7-O-glucuronide with lipid metabolism-related enzymes. These findings indicate that C. icaco L. seeds may be considered a promising source of bioactive molecules for the treatment and management of early phases of dyslipidaemias, as evidenced in an acute model, but their full potential in chronic stages merits further research.

Blood can clot into anomalous, fibrinolysis-resistant forms that arise from prothrombotic seeding areas, including damaged cellular debris and membrane-derived surfaces, giving rise to what we have termed fibrinaloid microclot complexes (colloquially: microclots). Their proteolytic resistance is due in part to the fact that they are amyloid in nature, and they can also entrap inhibitors of proteolysis. They consist of a variety of proteins besides the expected fibrin, and are highly enriched for other amyloidogenic proteins (in contrast to normal clots, whose proteome largely reflects the soluble plasma proteome). They also contain DNA in the form of neutrophil extracellular traps (NETs). Importantly, fibrinaloid microclot complexes are heterogeneous structures comprising multiple phenotypic forms, including those that nucleate and grow on cellular debris such as damaged membranes, microparticles, and immune-derived material. We consider that these debris-associated complexes can act as catalytic scaffolds that recruit fibrin(ogen) and inflammatory molecules, thereby amplifying amyloidogenic transformation and prothrombotic activity. Fibrinaloid microclot complexes have been reported in a widening range of chronic inflammatory and thrombo-inflammatory diseases in which they have been sought, and are highly enriched for amyloidogenic proteins. Additionally, the thrombi extracted from ischaemic stroke also contain proteins in an amyloid form. One mechanism that explains how such macroclots can form and block arteries larger than any leading to them is that this occurs via the accretion of microclots that already contain amyloid. We here show that these microclots exhibit a classical ‘apple-green’ birefringence when stained with the dye Congo red. It is now important to determine whether inhibiting amyloid-forming clot transitions has therapeutic value.

Cognitive decline is a hallmark of brain ageing. Leucocyte telomere length (LTL) has emerged as a candidate biomarker related to brain ageing and neurodegeneration; however, reported associations with cognition and brain structure vary across cohorts. Long-chain omega-3 polyunsaturated fatty acids (PUFA), notably docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), exert anti-inflammatory and antioxidant effects that may, in some contexts, relate to slower telomere attrition. Here, we synthesise evidence on n-3 PUFA, telomere biology and cognitive outcomes, integrating clinical, epidemiologic and experimental data. We emphasise biological plausibility (oxidative stress/inflammation, membrane remodelling, mitochondrial function and expression of telomerase reverse transcriptase (TERT) through PI3K/Akt/mTOR, NRF2 and epigenetic modifications) while acknowledging heterogeneous human findings and methodological considerations (assay variability, life-course timing, cognitive domains and biomarker stratification). We outline priorities for future studies to clarify causal pathways and inform dietary strategies that support healthy cognitive ageing.

Butachlor is a herbicide extensively employed in rice (Oryza sativa L.) cultivation but historically under-investigated for its toxicological impacts on terrestrial vegetation. This study examines the dose-dependent effects of butachlor on the germination and antioxidant defense mechanisms in the seeds of Asian tape grass [Vallisneria natans (Lour.) H. Hara], an important submerged plant species widely distributed in the agricultural ponds. In a hydroponic setup, seeds were exposed to four concentrations of butachlor (0, 20, 200, and 2,000 μg ai L−1), and cultivated under controlled light conditions to quantify germination rates and assess oxidative stress responses. Our findings showed that butachlor concentrations up to 20 μg L−1 had no effect on the germination rate of V. natans seeds, while germination rates decreased by 6.0% and 8.7% at 200 and 2,000 μg L−1, respectively. At 2,000 μg L−1, malondialdehyde (MDA) content increased by 5.7 nmol g−1 FW, and catalase (CAT) activity declined by 21%, indicating oxidative damage. Additionally, the antioxidants proline (Pro) and glutathione (GSH) were upregulated under 20 μg L−1 butachlor treatment after 12 h, contributing to reactive oxygen species (ROS) scavenging and cellular stability. This study highlights the nuanced interactions between butachlor exposure and the antioxidant defenses in V. natans, providing valuable insights into the ecological impacts of herbicide pollution. Understanding these interactions is crucial for development of sustainable agricultural practices and management of herbicide resistance in aquatic systems.

Catechins are bioactive flavanols commonly found in the fruits and leaves of plants, particularly the fresh tea leaves. This experimental study aims to evaluate the antioxidant properties of epigallocatechin-3-gallate, one of the most prominent catechins, and its ability to mitigate cadmium-induced oxidative stress. Eighty rats were randomly assigned to four groups of 20: an untreated control group (group 1), a catechin-treated group (group 2), a cadmium-exposed group (group 3), and a cadmium-catechin group (group 4). Group 2 rats received daily oral doses of catechin at 300 mg/kg body weight, while Group 3 rats were given an aqueous solution of cadmium chloride at a final concentration of 5 mg/kg body weight (b.w.) per day. Group 4 rats were treated with both catechin and cadmium chloride. The rats in Group 4 exhibited increased levels of total proteins and significant increases in antioxidant markers, including total thiols, glutathione, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, and catalase. Additionally, this group demonstrated significant decreases in blood cadmium levels and in the following enzymes: alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. They also demonstrated significant decreases in creatinine, blood urea nitrogen, urea, and bilirubin, as well as in oxidation markers (H2O2 and malondialdehyde), compared to the cadmium group (Group 3). Tissue homogenates from the livers and kidneys of Group 4 rats revealed similar results to those of the serum biochemical assay. Based on these findings, it can be concluded that catechin’s (ECGC) antioxidant properties significantly mitigate cadmium-induced oxidative stress.

As the global population ages, the prevalence of cognitive decline is rising, creating urgent demand for proactive strategies that support brain health and healthy ageing. Ergothioneine, a unique dietary amino-thione absorbed via the OCTN1 transporter, has recently gained attention for its potential as a neuroprotective, longevity-promoting compound. This review synthesizes growing evidence from observational, interventional and mechanistic studies. Observational data consistently associate low blood ergothioneine levels with cognitive impairment, neurodegenerative diseases, cardiovascular disorders, frailty and mortality. Interventional trials in older adults suggest that ergothioneine supplementation may improve cognition, memory, sleep quality and stabilize neurodegeneration biomarkers, with no safety concerns at doses up to 25 mg/day. Mechanistic studies reveal that ergothioneine acts through multiple pathways: mitigating oxidative stress, reducing neuroinflammation, preserving mitochondrial function and potentially modulating neurogenesis and NAD+ metabolism, although some mechanisms require further investigation. Beyond cognition, ergothioneine shows promise in supporting other physiological systems relevant to ageing, including cardiovascular, metabolic, gut, eye, auditory, liver, kidney, immune, skin and lung health. Together, current evidence positions ergothioneine as a promising nutritional intervention for promoting cognitive resilience and systemic health in ageing, although larger, long-term interventional trials are needed to confirm causality and optimize use.

Although numerous clinical studies suggest that ginseng supplementation may benefit CVD risk factors, results remain inconclusive. This systematic review and meta-analysis evaluated the effects of ginseng supplementation on CVD-related risk factors. Relevant studies were identified through electronic searches in Embase, Web of Science, Scopus, PubMed and CENTRAL up to August 2024. Statistical analyses, including a random effects model, meta-regression and non-linear modelling, were used to assess heterogeneity, dose–response relationships and the overall effects of ginseng supplementation. A total of 70 studies, published between 1998 and 2024 and involving 4506 participants, were included. Ginseng supplementation significantly affected several biochemical markers, including high-sensitivity C-reactive protein (standardised mean difference (SMD): −0·23; 95 % CI: −0·38, −0·08; P = 0·002), gamma-glutamyl transferase (SMD: −0·20; 95 % CI: −0·36, −0·04; P = 0·015), glutathione reductase (SMD: 0·90; 95 % CI: 0·38, 1·42; P = 0·001), reactive oxygen species (SMD: −0·94; 95 % CI: −1·27, −0·60; P < 0·001) and superoxide dismutase (SMD: 0·48; 95 % CI: 0·10, 0·87; P = 0·014). Meta-regression analysis showed significant linear associations between ginseng dosage and Homeostatic Model Assessment for Insulin Resistance (P = 0·044) and between supplementation duration and malondialdehyde (P = 0·007). Dose–response analysis revealed significant associations between ginseng dose and fasting blood glucose (P < 0·001), high-sensitivity C-reactive protein (P = 0·043), IL-6 (P = 0·041), diastolic blood pressure (P = 0·022), IL-10 (P = 0·048), fasting insulin (P = 0·012) and total protein (P = 0·010). Supplementation duration was positively associated with malondialdehyde levels (P = 0·008). Ginseng supplementation was associated with improvements in inflammatory markers, liver function and oxidative stress parameters. No significant effects were observed on anthropometric indices, blood pressure, glycaemic profile, lipid profile, adipokines or heart rate.