Search Results (10,692)

Background: Vitamin D deficiency has been implicated in disturbances of glucose and lipid metabolism, particularly in occupational groups with limited sunlight exposure. This study aimed to examine the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and markers of carbohydrate and lipid metabolism in salt mine workers. Methods: This cross-sectional study involved 62 male salt miners (aged 25–63 years), stratified by work depth (surface, ≤750 m, and >750 m). Anthropometric characteristics, body composition, cardiorespiratory fitness (VO_2max), and biochemical parameters were assessed. Blood analyses included fasting glucose, insulin, lipid profile, TSH, and 25(OH)D. Insulin resistance was evaluated via the HOMA-IR index. Results: The cohort exhibited a high prevalence of overweight and obesity (mean BMI > 28 kg/m²). Significant differences in VO_2max were observed between groups (p < 0.05). Elevated fasting glucose (>100 mg/dL) was observed in 47% of participants, and 22% presented HOMA-IR values > 2.5. In the regression model, vitamin D supplementation was the strongest predictor of 25(OH)D levels, explaining 25.5% of its variance. The addition of HDL cholesterol increased the explained variance to 35.6%, whereas HOMA-IR contributed an additional 3.9% (p = 0.094). Conclusions: In salt miners, insufficient vitamin D status coexists with excess adiposity and impaired glucose homeostasis. Serum 25(OH)D was more strongly associated with supplementation and HDL-C than with HOMA-IR. These findings suggest that monitoring vitamin D status is relevant in the occupational health evaluation of this group. Full article

Background/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg/dL for DKA patients and 1252.8 mg/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusion: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications. Full article

Peripheral nerve injury is a leading cause of disability, which can result in partial or complete loss of motor, sensory, and autonomic function, and currently, there is no effective treatment for this incapacitating condition. It is important to identify new compounds that enable rapid and complete functional recovery. This study evaluated the effects of isorhamnetin (ISO) on functional rehabilitation in a mouse model of sciatic nerve injury. A total of 30 BALB/c mice, aged 8–10 weeks, were randomly assigned to three groups: sham, control, and treatment (n = 10/group). The mice in the ISO and Ctrl groups were operated on, whilst the animals in the sham group had their sciatic nerves exposed but left intact without crushing. The Ctrl and Sham groups received DMSO and normal saline intraperitoneally in equal volumes. In contrast, the ISO-treated group received ISO (10 mg/kg) dissolved in DMSO intraperitoneally from the day of nerve crush until the end of the study. All groups were fed regular chow and provided with sufficient water throughout the experiment. Behavioural analyses evaluated sensorimotor function recovery. Biochemical and haematological assays quantified oxidative stress markers and total blood count, while morphometric analysis determined structural recovery of muscle fibers. Nerve regeneration was indirectly evaluated by analyzing S100β protein levels and proinflammatory cytokines (IL-6 and TNF-α) expression. In the mouse model, ISO treatment resulted in substantial improvement in sensorimotor function recovery (p < 0.001). A substantial difference (p < 0.001) in blood glucose levels and oxidative stress markers was observed among all groups. The treated group displayed a remarkable improvement in the cross-sectional area of muscle fibers. At the end of the study, it was noted that ISO treatment significantly downregulated the expression of S100β, TNF-α, and IL-6, suggesting a positive impact of ISO on nerve regeneration. These findings indicate that ISO expedites the restoration of sensorimotor function following sciatic nerve injury by modulating S100β and proinflammatory cytokine expression and improving oxidative stress. Full article

The diagnosis of type 2 diabetes using classical clinical and laboratory biomarkers (HbA1c, glucose, lipids, BMI, and blood pressure) is a classification by symptoms and does not provide insight into the underlying pathophysiological disorders (insulin resistance, ß-cell dysfunction, visceral adipose tissue hormonal secretion, and chronic systemic inflammation). A better understanding of these disorders may help in the selection of appropriate and potentially more successful personalized therapeutic interventions. Based on extensive clinical trial experience, a method for individual phenotyping and consecutive personalized diabetes therapy has been developed in our practice, which we have been using for more than 15 years and would like to share for discussion and debate. In this Part 1, the pathophysiological background and diagnostic approach to phenotyping is described. A consecutive Part 2 will present the translation of the phenotyping result into a personalized diabetes therapy, and another consecutive Part 3 will provide more comprehensive real-world patient observations when practicing this concept. This article is intended as a discussion/concept paper and does not present unpublished patient-level outcome data or formal effectiveness analyses. Prospective validation studies are needed to evaluate the clinical utility of this phenotype-based framework. Full article

Dietary protein oxidation impairs animal health, yet effective interventions remain limited. This study investigated whether quercetin (Q) supplementation protects against protein-oxidized soybean meal (OS)-induced oxidative stress and inflammatory injury in rats. A 2 × 2 factorial experiment was conducted with 48 three-week-old Sprague-Dawley rats randomly assigned to four dietary treatments (n = 12): fresh soybean meal (FS), FS + 400 mg/kg Q, OS, and OS + 400 mg/kg Q for 28 days. Serum biochemistry, intestinal and hepatic histology, antioxidant status, inflammatory markers, and transcriptomic pathways were analyzed. As a result, OS feeding elevated serum glucose and urea nitrogen, induced duodenal, jejunal and hepatic lesions, reduced total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) activity, glutathione (GSH) level, increased reactive oxygen species (ROS) and malondialdehyde (MDA) content (p < 0.05), and increased IgG and IL-6 levels (p < 0.05). Transcriptomic analysis revealed upregulation of heme biosynthesis and ROS synthesis pathways in jejunum and liver (p < 0.05). Q supplementation mitigated these adverse effects by improving antioxidant status, reducing inflammatory lesions, downregulating heme and ROS pathways, and normalizing the expression of key genes (Ccl20, RT1-M2) and protein (Ccl20) in jejunum (p < 0.05), and key genes (Duox1, Cyp4a2) and protein (Duox1) in liver (p < 0.05). These findings demonstrate that Q alleviates OS-induced oxidative stress, inflammation, and tissue damage through the modulation of heme and ROS pathways. Full article

Managing blood glucose in type 1 diabetes (T1D) remains a daily clinical challenge, and accurate short-term prediction of glucose levels can meaningfully improve insulin dosing decisions while reducing the risk of dangerous hypoglycaemic episodes. Although numerous machine learning approaches have been proposed for this task, comparing their relative merits is difficult because published studies differ widely in datasets, preprocessing choices, and evaluation criteria. In this work, we address this research gap by benchmarking ten machine learning methods—from a naïve persistence baseline through classical linear regressors, gradient-boosted ensembles, and recurrent neural networks to a novel hybrid that couples LightGBM with stochastic differential equation (SDE)-based glucose–insulin simulation—on two multi-patient datasets comprising 34 T1D subjects, across prediction horizons of 15, 30, 60, and 120 min. Every method is trained and tested under identical preprocessing and temporal splitting conditions to ensure a fair comparison. The proposed Hybrid LightGBM-SDE model consistently outperforms all alternatives, recording RMSE values of 22.42 mg/dL at 15 min, 28.74 mg/dL at 30 min, 33.89 mg/dL at 60 min, and 37.22 mg/dL at 120 min—an improvement of between 13.6% and 27.0% relative to standalone LightGBM. At the clinically important 30 min horizon, 99.7% of predictions lie within the acceptable A and B zones of the Clarke Error Grid. Wilcoxon signed-rank tests confirm that performance differences are statistically significant (p < 10⁻¹⁰), and SHAP-based analysis shows that the SDE-derived simulation features are among the most influential predictors, especially at longer horizons. All source code and evaluation scripts are publicly released to support reproducibility. Due to temporary data access constraints, all experiments reported here use physics-based synthetic datasets generated from the Bergman minimal model, replicating the structural properties of the D1NAMO and HUPA-UCM collections; validation on the original clinical recordings is planned. Among the two synthetic datasets, the D1NAMO-equivalent cohort (nine patients) proves more challenging, with systematically higher per-patient RMSE variance. The clinically acceptable prediction accuracy at the 30 min horizon (99.7% in Clarke zones A + B) suggests potential for integration into insulin dosing decision-support systems. Full article

Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy. Full article

Background: Tirzepatide is a novel therapeutic option for the management of metabolic disorders which has started to be implemented in routine practice. The study aimed to analyze the effectiveness of tirzepatide use and patient education in the field of healthy eating and weight loss, based on real-life data from the practice of a primary care physician, in metabolic syndrome (MetSyn) patients during a one-year follow-up period. Methods: This is a retrospective study based on real-life data of 118 MetSyn patients who were under the supervision of a general practitioner (GP). Analysis was conducted on 62 patients supported by trizepatide (2.5 mg for 4 weeks, then 5 mg for 4 weeks and 7 mg for 46 weeks) with dietary education and 56 patients that underwent dietary education with motivation only. Lipid profile, glucose level and blood pressure were assessed. Body Mass Index (BMI), waist-to-height ratio (WHtR), A Body Shape Index (ABSI), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI) and Body Roundness Index (BRI) were calculated. The KomPAN^® questionnaire was used for dietary assessment and WHO Quality of Life-BREF for the quality of life assessment at 52 weeks. Results: Patients from both groups significantly reduced their body weight and WC and the values of the following indices: BMI, WHtR, ABSI, LAP and BRI. A significant increase in LDL cholesterol and triglyceride values was observed in both groups and a significant decrease in glucose level only in the group with tirzepatide combined with dietary modification. Energy value, energy density of food and nutrient intake did not differ between groups, while the intensity of beneficial nutritional features (pHDI-10) was low. Significant differences in patients’ QoL were observed, especially in the domain related to mental health (higher in trizepatide + diet group). Conclusions: Support in primary care by a physician was successful from a long-term perspective in the group using tirzepatide in combination with diet modification as well as in the group based on dietary modification only. The data do not indicate a significant advantage of any one approach for patients, prioritizing an individualized approach to treatment. Full article

Two-dimensional Ti₃C₂O₂ MXene has emerged as a promising electrode material for non-enzymatic glucose sensing due to its metallic conductivity and biocompatibility. However, the atomic-scale sensing mechanism remains unclear. This DFT study uses the PBE functional with the D3(BJ) dispersion correction to elucidate glucose–MXene interactions under idealized vacuum conditions. Pristine Ti₃C₂O₂ shows metallic behavior with a density of states of about 8.2 states per electron volt at the Fermi level, dominated by Ti 3d states. β-d-glucose adsorbs onto the surface through hydrogen bonding, with an adsorption energy of −0.82 eV at a separation distance of 2.8 angstroms. Bader analysis indicates a transfer of about 0.15 electrons from MXene to glucose, resulting in a Fermi level shift of about −0.15 eV and an 18% reduction in the density of states at the Fermi level. These changes correspond to an estimated sensitivity of approximately 0.6 μA mM⁻¹ cm⁻² and a detection limit of about 17 µM, consistent with reported experimental performance of MXene-based sensors. Comparative adsorption calculations for common sweat interferents yield −0.45 eV for lactate and −0.25 eV for urea, indicating weaker interfacial affinity than glucose; these values reflect thermodynamic binding strength and possible surface occupation rather than definitive electrochemical selectivity, which additionally depends on redox potential, electron-transfer kinetics, and operating bias. We acknowledge three main limitations: first, the model considers only pure oxygen termination rather than mixed oxygen, hydroxyl, and fluorine terminations; second, the calculations are performed under vacuum rather than in aqueous conditions; third, the study is based on static zero kelvin structures rather than finite temperature dynamics. Despite these idealizations, the results provide baseline mechanistic insights to support rational design of MXene-based glucose sensors. Full article

Background/Objectives: Vitamin D plays an important role in glucose metabolism, lipid regulation, and inflammatory processes, and has been implicated in cardiometabolic health. However, its associations with specific metabolic biomarkers remain inconsistent, particularly in older adults. This study aimed to examine whether vitamin D deficiency is differentially associated with multiple metabolic biomarkers in a nationally representative sample of older adults. Methods: This cross-sectional study used data from the 2024 Korea National Health and Nutrition Examination Survey, including 1806 adults aged ≥65 years. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D levels < 20 ng/mL. Metabolic biomarkers included fasting glucose, glycated hemoglobin (HbA1c), triglycerides, C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), waist circumference, and body mass index (BMI). Complex sample linear regression analyses were performed with sequential adjustment for sociodemographic factors, health behaviors, and comorbidities. Results: In unadjusted analyses, vitamin D deficiency was associated with adverse metabolic profiles, including higher fasting glucose, HbA1c, triglycerides, waist circumference, and CRP levels, and lower HDL-C levels. After adjustment for sociodemographic factors, health behaviors, and comorbidities, significant associations remained for HbA1c (β = 0.10, p = 0.034), triglycerides (β = 0.10, p = 0.003), and waist circumference (β = 1.21, p = 0.040). No significant associations were observed for fasting glucose, HDL-C, CRP, or BMI. Conclusions: Vitamin D deficiency was independently associated with poorer long-term glycemic status, hypertriglyceridemia, and central adiposity in older adults, but not with other metabolic markers after adjustment. These findings suggest that the metabolic correlates of vitamin D deficiency may be domain-specific rather than generalized. Longitudinal and interventional studies are needed to clarify causality and underlying mechanisms. Full article

Environmental temperature-induced metabolic changes in dams can be reflected by alterations in metabolomic and fatty acid profiles in colostrum. The colostrum from 13 Black Bengal (BB) dams was collected on the day of parturition at two consecutive parities during the hot conditions (HCs) of summer or rainy seasons and the cold conditions (CCs) of winter. The metabolomic and fatty acid profiles were analyzed using nuclear magnetic resonance (NMR) and gas chromatography–mass spectrometry, respectively. The results showed significantly higher sarcosine, tyrosine, citrate, succinate, galactose, acetylglucosamine, carnitine, choline, glycerophosphocholine, and trimethylamine N-oxide during CCs than HCs; potential discriminant metabolites according to VIP scores were sarcosine, succinate, and choline. Colostrum from CCs had significantly lower levels of saturated fatty acids (SFAs), including butyric acid (C4:0), myristic acid (C14:0), and pentadecanoic acid (C15:0), but higher omega-9 monounsaturated fatty acids (MUFAs), especially oleic acid (C18:1n9c), elaidic acid (C18:1n9t), and eicosenoic acid (C20:1n9), than in HC. Linoleic acid (C18:2n6c) and the omega 6/omega 3 PUFA ratio were higher during CCs than HCs. It is concluded that a metabolic shift for nutrient utilization occurs, from glucose during HCs toward fat during CCs, which may not be due to the diet but rather neurohumoral alterations occurring during temperature adaptation. Full article

Introduction: Oxidative stress and inflammation are major factors linked to obesity and metabolic dysfunction, leading to a significantly higher risk of related diseases. Atorvastatin and liraglutide possess lipid-lowering, antioxidant, and anti-inflammatory effects that could synergistically improve obesity-related perturbations through modulation of the Nrf2/HO-1 signaling pathway. Methodology: We assessed liraglutide’s pharmacological potential in extending atorvastatin’s benefit on obesity, hyperlipidemia, and fatty liver in rats fed a high-fat diet (HFD) for 12 weeks. We specifically evaluated the effects of liraglutide treatment on atorvastatin-induced anti-inflammatory and antioxidant mechanisms, with a particular focus on Nrf2/HO 1 modulation in adipose and hepatic tissue. In silico analyses, including molecular docking and AlphaFold- Multimer modeling, evaluated the binding affinities of atorvastatin and liraglutide to Nrf2 and HO 1. Results: Compared to ND, the HFD-fed rats had a significantly higher final body weight (362.4 ± 12.7 g vs. 245.6 ± 9.8 g in ND, p < 0.05). There was a marked increase in serum total cholesterol (178.6 ± 9.2 mg/dL vs. 98.3 ± 6.4), fasting glucose (340.1 ± 8.2 mg/dL vs. 82.3 ± 3.1), HbA1c (7.8 ± 0.3 vs. 4.5 ± 0.2), and hepatic COX-2 expression (99.9 ± 6.3 vs 19.6 ± 2.4). The oxidative stress markers were also disturbed, as indicated by SOD (42.5 ± 3.1 vs. 95.2 ± 4.6 U/mg protein), GSH (18.3 ± 1.5 vs. 42.7 ± 2.8 nmol/mg), and p62 (0.005 ± 0.001 vs. 0.125 ± 0.01). Atorvastatin lowered cholesterol (121.2 ± 7.5 mg/dL), COX-2 (61.3 ± 3.3), and body weight (301.7 ± 11.5 g) compared to HFD. Meanwhile, liraglutide caused a greater reduction in body weight (268.5 ± 10.3 g), glucose (112.5 ± 6.7 mg/dL), and COX-2 (42.2 ± 2.9) than atorvastatin. The combination therapy produced the most significant effects, returning body weight (253.6 ± 9.1 g) to baseline, normalizing glucose and lipids, reducing COX-2 to 22.9 ± 2.0, and reactivating the Nrf2/HO-1 pathway, as shown by increased HO-1 expression and the restoration of p62 levels (0.078 ± 0.004). In silico analyses suggest that atorvastatin favorably binds to Nrf2 and HO-1, while liraglutide interacts with structurally relevant interfaces on these proteins, providing a mechanistic basis for their complementary antioxidant and cytoprotective effects. Conclusions: Our findings support targeting the Nrf2/HO-1 signaling pathway as a potential therapy for reversing hyperlipidemia and preventing mediators of inflammation and oxidative stress damage in the liver tissue. The evidence of increased efficacy observed with the combined atorvastatin and liraglutide supports a potential novel understanding of the complementary effects of atorvastatin and liraglutide. This finding requires further investigation to elucidate the combination’s therapeutic advantages in treating metabolic disorder scenarios. Full article

Nicotinamide mononucleotide (NMN), a direct precursor of the essential coenzyme nicotinamide adenine dinucleotide (NAD⁺), confers anti-aging effects and multiple health benefits. Engineered microorganisms represent a promising platform for sustainable industrial production of NMN. Here, the previously reported NMN-producing strain NMN008 was engineered to co-utilize glucose and glycerol for the biosynthesis of NMN from nicotinamide (NAM). First, the glycolytic genes pgi and pykA/pykF were sequentially deleted to disrupt glucose catabolism through the glycolytic pathway, thereby potentially improving precursor availability for NMN biosynthesis. Second, a feedback-resistant glycerol kinase mutant (glpK*) was introduced to enhance glycerol utilization, aiming to compensate for the growth defects associated with impaired glycolysis. These modifications enabled glycerol to primarily support cell growth and energy metabolism, while improving glucose allocation toward NMN biosynthesis by reducing its competitive consumption through glycolysis. As a result, the final strain achieved an NMN titer of 32.92 g/L in a 2 L bioreactor, representing a 26.28% increase in NMN production and a substantial 34.48% improvement in carbon conversion efficiency. Our research provides an effective strategy to achieve industrial-scale production of NMN, laying a foundation for the widespread application of NMN. Full article

Ferroptosis, a type of iron overload-induced cell death, is involved in diabetes-induced testicular dysfunction. Hence, this study was designed to investigate, for the first time, the impact of lipoxin A4 (LXA4) administration on testicular tissue in diabetic rats and explore its probable role in regulating ferroptosis in comparison with the standard ferroptosis inhibitor (ferrostatin-1, Fer-1). Albino rats of Wistar strain were divided into a control group, a type II diabetes mellitus (DM) group, a DM + Fer-1group, and a DM + LXA4 group. Serum levels of iron, insulin, glucose, total cholesterol, triglycerides, and testosterone were assayed. Testicular tissue markers of oxidative stress, ferroptosis, and inflammation were also assessed by different methods. Our results confirmed diabetes-induced testicular injury and disruption of its function via inducement of ferroptosis, but this was ameliorated with LXA4 and Fer-1 administration. However, Fer-1 showed a greater protective effect compared to LXA4 under the conditions of this study. We concluded that LXA4 partially secured the testicular tissue of diabetic rats against ferroptosis via augmenting the antioxidant Nrf2/SLC7A11/GPX4 pathway. Therefore, LXA4 may have a possible protective effect on the testicular tissue of diabetic patients. Full article

Thermotolerant methylotrophic yeast Ogataea parapolymorpha is a promising host for high-temperature bioprocesses, yet the effects of carbon source and exogenous carbohydrates on their heat response remain poorly understood. We investigated how growth on glucose, glycerol, or methanol, short-term thermoadaptation (45 °C, 2 h), and supplementation with trehalose, sucrose, maltose, or xylose affect thermotolerance (55 °C, 30 min) and intracellular trehalose content. Thermoadaptation increased survival on all carbon sources and was accompanied by substantial trehalose accumulation in glucose- and glycerol-grown cells, but only minor trehalose accumulation in methanol-grown cells. Carbohydrate supplementation improved survival only in methanol-grown cultures. Under these conditions, trehalose, sucrose, and maltose increased intracellular trehalose levels, whereas xylose enhanced survival without a comparable increase in trehalose. These results show that the heat-stress response of O. parapolymorpha is strongly carbon source-dependent and that the protective effects of carbohydrate supplementation in methanol-grown cells cannot be explained by trehalose accumulation alone. Full article