Systemic Oxidative Stress Research Articles

Lactiplantibacillus plantarum Y44 Complex Fermented Milk Regulates Lipid Metabolism in Mice Fed with High-Fat Diet by Modulating Gut Microbiota.

The benefits of fermented milk containing Lactiplantibacillus plantarum (L. plantarum) Y44, known for its weight loss properties, remain unclear. For this, we evaluated the effects of the complex fermented milk (Y44-CFM), obtained through the cofermentation of cow's milk and soybean milk with L. plantarum Y44 and traditional starters, on high-fat diet (HFD)-fed C57BL/6 mice. Our study found that the oral administration of Y44-CFM significantly reduced body weight gain and hepatic lipid accumulation in HFD-fed mice while also mitigating liver injury. Additionally, Y44-CFM regulated the expression of enzymes associated with lipid metabolism in the serum, as well as the corresponding or related genes in the liver, such as fatty acid synthase. Furthermore, HFD-induced systemic inflammation, oxidative stress, and intestinal barrier dysfunction were improved. The primary alterations in hepatic metabolism involved glycerophospholipids and amino acids, including the biosynthesis of valine, leucine, and isoleucine. The diversity and overall structure of the gut microbiota were also regulated, resulting in a significant decrease in the ratio of Firmicutes to Bacteroidetes (F/B) and unclassified_f_Lachnospiraceae, along with a notable increase in Oscillospiraceae. The correlation analysis indicated that Y44-CFM influenced hepatic lipid metabolism by mediating intestinal flora and its production of short-chain fatty acids, ultimately leading to weight reduction.

Dietary exposure to di (2-ethylhexyl) phthalate (DEHP) for 6months alters markers of female reproductive aging in mice.

The female reproductive system ages before any other physiological system, making it a sensitive indicator of aging. Early reproductive aging is associated with the early onset of infertility and an increased risk of several diseases. During aging, systemic and reproductive oxidative stress and inflammation levels increase through inflammasome activation, leading to ovarian follicle loss. Other markers of reproductive aging include increased fibrosis and shortening of telomeres in ovarian cells. The factors that accelerate reproductive aging are unclear, but likely involve exposure to endocrine-disrupting chemicals such as phthalates. Di(2-ethylhexyl) phthalate (DEHP) is a widely used phthalate and humans are exposed to it daily. Several studies show that DEHP induces reproductive toxicity by affecting estrous cyclicity, follicle numbers, and hormone levels. However, little is known about the mechanisms underlying DEHP-induced early onset of reproductive aging. Thus, this study tested the hypothesis that dietary exposure to DEHP induces early reproductive aging by affecting inflammation, fibrosis, and the expression of telomere regulators and antioxidant enzymes. Adult CD-1 female mice were exposed to vehicle (corn oil) or DEHP (0.5, 1.5, or 1500ppm) via the chow for six months. Exposure to DEHP increased the expression of antioxidant enzymes and Casp3, increased expression of telomere-associated genes, and increased fibrosis levels in the ovary. In addition, DEHP exposure for 6months altered ovarian and systemic inflammatory status. Collectively, our novel data suggest that 6-month dietary exposure to DEHP may accelerate reproductive aging by affecting several reproductive aging markers in female mice.

CXCL5 inhibition ameliorates acute kidney injury and prevents the progression from acute kidney injury to chronic kidney disease.

Acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD). CXCL5 is upregulated in kidney diseases. We aimed to investigate the direct effect of CXCL5 on the pathology of AKI. Serum and renal expression of CXCL5 were increased in animals with renal ischemia-reperfusion injury or unilateral ureteral obstruction. CXCL5-knockout mice exhibited reduced systemic oxidative stress and preserved renal function in the acute and chronic phases of AKI, as evidenced by reductions in serum BUN and creatinine levels, the urinary albumin-to-creatinine ratio, and the kidney-to-body weight ratio. CXCL5-knockout mice improved AKI-induced tubular injury and fibrosis, reduced renal macrophage infiltration, and reduced expression of NADPH oxidase and inflammatory and fibrotic proteins. CXCL5 activated p47 to upregulate ROS generation and induce cellular damages through CXCR2. CXCL5 knockdown exerted antioxidative, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects on hypoxia-reoxygenation-stimulated renal proximal tubular epithelial cells. Clinical data indicated elevated circulating and renal CXCL5 in CKD patients, and renal CXCL5 was correlated with increased renal fibrosis and decreased estimated glomerular filtration rate. Altogether, CXCL5 levels increased in experimental AKI and clinical CKD, and in vivo and in vitro CXCL5 inhibition may reduce acute tubular injury and prevent the subsequent progression from AKI to CKD.

Experimental Periodontitis Increases Anxious Behavior and Worsens Cognitive Aspects and Systemic Oxidative Stress in Wistar Rats.

Periodontitis (PD) has the potential to induce systemic changes that affect both physical and behavioral aspects. These alterations may be associated with changes in both the inflammatory profile and the oxidative stress status of individuals with PD. Therefore, we aimed to evaluate the effects of PD on oxidative stress, as well as on behavioral parameters and cognitive impairment, in a preclinical model. Twenty-four male Wistar rats were randomly assigned to PD and sham groups. PD was induced by the ligature protocol for 14 days. Behavioral tests were initiated on the 9th day of the experiment to evaluate anxious behavior and cognition (learning and memory). After euthanasia, oxidative stress was evaluated in the gums, blood, hippocampus, and amygdala. Alveolar bone loss, bone microstructure, and elemental compositions of the mandibular bone were also assessed. PD increased alveolar bone loss, reduced the calcium and phosphorus content in the mandibular bone, and increased anxiety-like behavior and cognitive decline (p < 0.05). Furthermore, PD significantly affected the redox balance, as evidenced by increased total antioxidant capacity (TAC) in the gingiva and hippocampus (p < 0.05). It also led to increased lipid peroxidation in the gingiva and erythrocytes (p < 0.05), decreased antioxidant defenses in erythrocytes (superoxide dismutase) and the hippocampus (catalase), and increased antioxidant activity (catalase) in the amygdala (p < 0.05). PD resulted in cognitive alterations, including impairments in spatial learning and memory, as well as increased anxious behavior, likely due to redox imbalance in rats.

Changes in blood metabolomes as potential biomarkers for severity and prognosis in doxorubicin-induced heart failure: a study in HER2-positive and HER2-negative breast cancer patients

Abstract Background The use of doxorubicin for breast cancer treatment is often limited due to cardiotoxicity. Doxorubicin was shown to cause the alterations of cardiac metabolome levels in doxorubicin-treated rats. Interestingly, these changes were robustly associated with the development of doxorubicin-induced heart failure. Unfortunately, measurements of cardiac metabolome levels are rarely possible in humans. Hence, non-invasive biomarkers as representatives of doxorubicin-induced heart failure are required in clinical research and practice. Human epidermal growth factor receptor 2 (HER2) is a point of interest in breast cancer treatment. HER2 is associated with tumor aggressiveness. However, it was observed that HER2 protected against systemic oxidative stress and dilated cardiomyopathy. Therefore, we hypothesized that the alterations of blood metabolome levels and cardiac functions following doxorubicin treatment were different between HER2-positive and HER2-negative breast cancer patients. Purpose We determined the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced heart failure. In addition, the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients were compared. Methods HER2-positive (n=37) and HER2-negative (n=37) breast cancer patients were enrolled. Echocardiography, heart rate variability, and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at 3 months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all 3 time points was processed for measuring cardiac injury markers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment was also processed for measuring oxidative stress in peripheral blood mononuclear cells using flow cytometry and 85 metabolome levels in plasma using mass spectrometry-based targeted metabolomics. Results Cardiac injury and systolic dysfunction at 2 weeks after completion of doxorubicin treatment were comparable between HER2-positive and HER2-negative breast cancer patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively (Figure). Interestingly, the changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment (Figure). Conclusions The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, which might be served as severity and prognostic markers of doxorubicin-induced heart failure.

Monocytic mitochondrial dysfunction and impaired monocytic bioenergetic profile in patients with heart failure symptoms in post-COVID syndrome

Abstract Introduction/Purpose Approximately 35% of COVD-19 patients have persistent symptoms similar to congestive heart failure. The so called post-Covid syndrome, which includes symptoms such as dyspnea and angina pectoris, is presumably associated to cellular metabolism and oxidative stress, yet whether mitochondrial function is impaired in post-COVID patients is still unclear. We thus investigated the mitochondrial function in monocytes of symptomatic post-COVID patients compared to matched controls. Methods Patients with persisting cardiac symptoms in their daily activities and diagnosed with post-COVID syndrome (n=14) were recruited and matched with unaffected controls (n=10) for age, sex and cardiovascular risk factors. Structural heart disease was excluded through cardiac work-up (echocardiography, functional stress testing and when necessary coronary angiography). Primary monocytes were isolated using negative selection method. The bioenergetic status of the monocytes was assessed using the Agilent Seahorse XF Cell Mito Stress Test without and after modulation of reactive oxygen species (ROS) by buthionine sulfoximine (BSO). Results CD14++ monocytes isolated from post-COVID patients showed non-significantly increased basal proton leak (p=0.57), reduced maximal respiration, and reserved respiratory capacity (p=0.19) compared to controls. Induction of additional oxidative stress by ROS modulation revealed a significantly impaired bioenergetic profile of monocytes in terms of reduction of basal respiration (3-fold, p=0.0005), maximal respiration (4-fold, p=0.004) and spare respiratory capacity (5-fold, p=0.008). Conclusions We demonstrated an impaired bioenergetic profile of CD14++ monocytic mitochondria in patients suffering from heart failure symptoms following COVID-19 infection. Whether the findings provide a novel biomarker for measuring systemic oxidative stress conditions or whether there is a direct link between symptoms of post-COVID disease and monocytic function needs to be addressed in further studies.

Effects of smoking on local and systemic oxidative stress markers in individuals with periodontitis

Aim: This study aimed to assess the effects of smoking on systemic and local oxidative stress markers in patients with periodontitis. Methods: A total of 72 patients with periodontitis [38 smokers (S +P+), 34 non-smokers (S-P+)] and 54 periodontally healthy individuals [28 smokers (S+P-), 26 non-smokers (S-P-, control)] were included. After clinical measurements and samplings, the cotinine level, total antioxidant capacity (TAOC), total oxidative status (TOS), and malondialdehyde (MDA) level in the serum and saliva were determined, and the oxidative stress index (OSI) was calculated. Kruskal-Wallis and Mann-Whitney U tests were used for multiple and pairwise comparisons. Correlations were analyzed using Pearson correlation coefficient. P&lt;0.05 was considered statistically significant. Results: Smoking and periodontitis decreased the serum and salivary TAOCs and increased the TOS, MDA level, and OSI. The smokers with periodontitis had the lowest TAOC and the highest TOS, MDA level, and OSI, while the controls had the highest TAOC and the lowest TOS, MDA level, and OSI. The systemic and local effects of smoking seemed more pronounced than those of periodontitis in the oxidative stress study, but no significant difference was identified between the smoking (S+P-) and periodontitis (S-P+) groups. The clinical parameters and oxidative stress markers showed both substantial positive and negative relationships in all groups (p&lt;0.01). Conclusions: It can be concluded that smoking and periodontitis (S+P+) are associated with a decrease in serum and salivary TAOCs and an increase in TOS, MDA levels, and OSI. Smoking has a similar effect as periodontitis on local and systemic oxidative stress, and oxidative stress caused by smoking may be a significant factor in the pathophysiology of periodontitis.

Serum peroxiredoxin-4, a biomarker of oxidative stress, associates with new-onset chronic kidney disease: A population-based cohort study

BackgroundChronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population. MethodsThis study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, or both. ResultsBaseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42–1.04] U/L, median eGFR was 98 [IQR: 87–108] mL/min/1.73 m2, and median UAE was 8.1 [IQR: 6.0–12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3–11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21–1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06–1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings. ConclusionsThis study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.

The Link Between PM2.5 Exposure and Cardiovascular Health Risks

A major environmental contaminant with great consequences for cardiovascular health is particulate matter with a size less than 2.5 micrometres (PM2.5). The present studies on the worldwide influence of PM2.5 exposure on cardiovascular disease risks are synthesised in this review. Originating from both natural and manmade sources, PM2.5 can pass far into the respiratory tract and bloodstream to induce systemic inflammation, oxidative stress, and endothelial dysfunction. These systems help different cardiovascular diseases to grow and advance, so PM2.5 exposure becomes a major public health issue. Although some areas have improved in lowering PM2.5 levels, global average concentrations remain high and especially impact low- and middle-income nations. PM2.5-related cardiovascular hazards disproportionately affect vulnerable populations like the elderly, children, and economically poor areas. Effective interventions span policy-level reforms to community projects and personal protective actions. Effective case studies show how much focused efforts can help to enhance cardiovascular health results and air quality. Combining strict laws, creative monitoring technologies, and public health initiatives, this assessment emphasises the need of a multifarious approach to handle PM2.5 pollution. Future studies should concentrate on clarifying biological processes, pinpointing vulnerable individuals, and creating reasonably priced treatments to lower the worldwide prevalence of cardiovascular illness related with PM2.5 exposure. Keywords: PM2.5, Cardiovascular disease, Air pollution, Environmental health, Global health disparities

Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p &lt; 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.

Association between systemic zinc and oxidative stress levels and periodontal inflamed surface area.

Zinc is a structural component of some enzymes. The aim of this study was to evaluate the potential associations between serum zinc and oxidative stress levels and periodontal inflamed surface area (PISA). This study included 90 patients divided into three groups: a periodontitis group (P; n = 30), a gingivitis group (G; n = 30), and a periodontal health group (PH; n = 30). Periodontal parameters were recorded and PISA values were calculated. Serum total antioxidant status (TAS), total oxidant status (TOS), and zinc levels were examined biochemically. Oxidative stress index (OSI) levels were calculated. All clinical periodontal parameters, periodontal epithelium surface area, and PISA values were lower in the PH group than the P and G groups (p < 0.05). Serum zinc and TAS values were higher in the PH group than the P and G groups (p < 0.05). Serum TOS and OSI values were lower in the PH group than the G and P groups (p < 0.05). Serum OSI levels were lower in the G group than the P group (p < 0.05). PISA was associated with serum zinc (β = -28.96, 95% CI = (-38.95, -18.98), p < 0.001) and OSI (β = 89.84, 95% CI = (20.63, 159.05), p = 0.011) levels in the multivariate generalized linear model. PISA values were associated with decreasing serum zinc and TAS and increased TOS and OSI levels. Zinc deficiency can be associated with the severity of periodontal disease and higher oxidative stress levels.

Gingival inflammation and leukocyte-endothelium cell interactions in women with polycystic ovary syndrome.

Given the link between chronic inflammation and periodontal pathologies and increased cardiovascular risk, this study aims to investigate if gingivitis exacerbates the inflammatory response and subclinical atherosclerotic markers in women with polycystic ovary syndrome (PCOS). For this case-control study, women were assigned to three groups: two PCOS groups (with and without gingivitis) and a control group. Anthropometric and biochemical variables were determined, along with periodontal parameters (probing pocket depth [PPD], clinical attachment level [CAL], bleeding on probing [BOP], plaque index, calculus index, and tooth loss), systemic and neutrophil inflammatory markers (tumor necrosis factor alpha [TNFα], C-reactive protein [CRP], and c-Jun N-terminal kinase [JNK]), systemic oxidative stress mediators (myeloperoxidase [MPO] and glutathione), soluble cellular adhesion molecules, and neutrophil-endothelium cell interactions (rolling flux, velocity, and adhesion). Of 104 women recruited, 68 had PCOS, 24 of whom presented gingivitis, and 36 were controls. PCOS patients presented altered sexual hormone, lipid, and carbohydrate profiles. Levels of systemic inflammatory markers, MPO, and soluble platelet selectin (sP-selectin) were higher, and glutathione levels were lower in PCOS patients. BOP, plaque, and calculus index values were higher in PCOS patients with gingivitis. Neutrophils from PCOS patients showed increased JNK and decreased adhesion under flow conditions, with reduced rolling velocity and increased rolling flux and cellular adhesion, all of which were more pronounced in those with gingivitis. BOP was independently associated with rolling velocity, rolling flux, and cellular adhesion. Neutrophils of PCOS patients with gingivitis exhibit hyperactivity, promoting interaction with the endothelium and potentially contributing to atherosclerotic disease. Currently, there is a high prevalence of diseases that affect tooth-supporting tissues (periodontal diseases) and negatively influence the oral health and quality of life of the adult population. These pathologies lead to movement of the teeth and impairment of chewing function, eventually resulting in the loss of teeth. In recent years, the concept of periodontal medicine has arisen and consists of studying how periodontal diseases can influence our general inflammatory system and how systemic inflammatory pathologies can affect our oral health. In the present study, we evaluate a group of women with polycystic ovary syndrome (PCOS), a condition characterized by alterations of sex hormones and lipid profile and weight gain (body mass index). Our results show a high prevalence of gum inflammation among women with PCOS, which affects the interaction of their leukocytes and endothelial cells. The leukocytes of these women are hyper-responsive, presenting greater endothelial adhesion, lower flow velocity and enhanced rolling compared to those in a PCOS group without gum inflammation or controls. This study has generated a new line of research to analyze how neutrophils from patients with gingivitis exhibit hyperactivity, which promotes their interaction with the endothelium, thus contributing to the development of atherosclerotic disease.

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Metabolic Syndrome, Inflammation, Oxidative Stress, and Vitamin D Levels in Children and Adolescents with Obesity.

Metabolic syndrome (MetS) is associated with systemic inflammation, oxidative stress, and hypovitaminosis D. Our aim was to determine whether vitamin D mediates inflammation and oxidative stress, assessed through selected biomarkers, in children with obesity and/or MetS. Eighty children with normal weight, overweight, or obesity were analyzed for serum vitamin D, C-reactive protein, leukocytes, adiponectin, monocyte chemoattractant protein-1, myeloperoxidase, interferon-inducible T-cell alpha chemoattractant (I-TAC/CXCL11), superoxide dismutase-1, fasting lipid and glucose levels, ultrasound-measured abdominal fat thickness, waist circumference, body mass index and blood pressure. Children with obesity or overweight had lower vitamin D levels, increased blood pressure, visceral and subcutaneous fat thickness, and higher leukocytes, C-reactive protein, and myeloperoxidase levels. Those with MetS also had lower adiponectin levels. Vitamin D levels are negatively correlated with body mass index, waist circumference, and visceral and subcutaneous fat thickness. Correlation, mediation, and regression analyses showed no link between vitamin D and inflammatory/oxidative stress variables. The novel biomarker I-TAC did not correlate with obesity or vitamin D status. Our results indicate that vitamin D does not significantly mediate inflammation or oxidative stress in children and adolescents with obesity and/or MetS. Selected inflammation/oxidative stress biomarkers appear to be altered primarily due to obesity rather than vitamin D status.

Exploring the Interconnection between Metabolic Dysfunction and Gut Microbiome Dysbiosis in Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a prevalent joint disorder and the most common form of arthritis, affecting approximately 500 million people worldwide, or about 7% of the global population. Its pathogenesis involves a complex interplay between metabolic dysfunction and gut microbiome (GM) alterations. This review explores the relationship between metabolic disorders-such as obesity, diabetes, and dyslipidemia-and OA, highlighting their shared risk factors, including aging, sedentary lifestyle, and dietary habits. We further explore the role of GM dysbiosis in OA, elucidating how systemic inflammation, oxidative stress, and immune dysregulation driven by metabolic dysfunction and altered microbial metabolites contribute to OA progression. Additionally, the concept of "leaky gut syndrome" is discussed, illustrating how compromised gut barrier function exacerbates systemic and local joint inflammation. Therapeutic strategies targeting metabolic dysfunction and GM composition, including lifestyle interventions, pharmacological and non-pharmacological factors, and microbiota-targeted therapies, are reviewed for their potential to mitigate OA progression. Future research directions emphasize the importance of identifying novel biomarkers for OA risk and treatment response, adopting personalized treatment approaches, and integrating multiomics data to enhance our understanding of the metabolic-GM-OA connection and advance precision medicine in OA management.

Oxidative Stress Markers and Na,K-ATPase Enzyme Kinetics Are Altered in the Cerebellum of Zucker Diabetic Fatty fa/fa Rats: A Comparison with Lean fa/+ and Wistar Rats.

Type 2 diabetes mellitus has been referred to as being closely related to oxidative stress, which may affect brain functions and brain glucose metabolism due to its high metabolic activity and lipid-rich content. Na,K-ATPase is an essential enzyme maintaining intracellular homeostasis, with properties that can sensitively mirror various pathophysiological conditions such as diabetes. The goal of this study was to determine oxidative stress markers as well as Na,K-ATPase activities in the cerebellum of Zucker diabetic fatty (ZDF) rats depending on diabetes severity. The following groups of male rats were used: Wistar, ZDF Lean (fa/+), and ZDF (fa/fa) rats, arbitrarily divided according to glycemia into ZDF obese (ZO, less severe diabetes) and ZDF diabetic (ZOD, advanced diabetes) groups. In addition to basic biometry and biochemistry, oxidative stress markers were assessed in plasma and cerebellar tissues. The Na, K-ATPase enzyme activity was measured at varying ATP substrate concentrations. The results indicate significant differences in basic biometric and biochemical parameters within all the studied groups. Furthermore, oxidative damage was greater in the cerebellum of both ZDF (fa/fa) groups compared with the controls. Interestingly, Na,K-ATPase enzyme activity was highest to lowest in the following order: ZOD > ZO > Wistar > ZDF lean rats. In conclusion, an increase in systemic oxidative stress resulting from diabetic conditions has a significant impact on the cerebellar tissue independently of diabetes severity. The increased cerebellar Na,K-ATPase activity may reflect compensatory mechanisms in aged ZDF (fa/fa) animals, rather than indicating cerebellar neurodegeneration: a phenomenon that warrants further investigation.

Advances in the Insulin-Heart Axis: Current Therapies and Future Directions.

The insulin-heart axis plays a pivotal role in the pathophysiology of cardiovascular disease (CVD) in insulin-resistant states, including type 2 diabetes mellitus. Insulin resistance disrupts glucose and lipid metabolism, leading to systemic inflammation, oxidative stress, and atherogenesis, which contribute to heart failure (HF) and other CVDs. This review was conducted by systematically searching PubMed, Scopus, and Web of Science databases for peer-reviewed studies published in the past decade, focusing on therapeutic interventions targeting the insulin-heart axis. Studies were selected based on their relevance to insulin resistance, cardiovascular outcomes, and the efficacy of pharmacologic treatments. Key findings from the review highlight the efficacy of lifestyle modifications, such as dietary changes and physical activity, which remain the cornerstone of managing insulin resistance and improving cardiovascular outcomes. Moreover, pharmacologic interventions, such as metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, have shown efficacy in reducing cardiovascular risk by addressing metabolic dysfunction, reducing inflammation, and improving endothelial function. Furthermore, emerging treatments, such as angiotensin receptor-neprilysin inhibitors, and mechanical interventions like ventricular assist devices offer new avenues for managing HF in insulin-resistant patients. The potential of these therapies to improve left ventricular ejection fraction and reverse pathological cardiac remodeling highlights the importance of early intervention. However, challenges remain in optimizing treatment regimens and understanding the long-term cardiovascular effects of these agents. Future research should focus on personalized approaches that integrate lifestyle and pharmacologic therapies to effectively target the insulin-heart axis and mitigate the burden of cardiovascular complications in insulin-resistant populations.

Expiratory muscle strength training reduces oxidative stress and systemic inflammation in men with obstructive sleep apnea syndrome: a double-blinded, randomized parallel trial

Abstract Study Objectives This study aimed to evaluate and compare the effects of high and low-intensity expiratory muscle strength training (EMST) on disease severity, systemic inflammation, oxidative stress, respiratory muscle strength, exercise capacity, symptoms, daytime sleepiness, fatigue severity, and sleep quality in male patients with obstructive sleep apnea syndrome (OSAS). Methods Thirty-one male patients diagnosed with moderate OSAS were included in this double-blind, randomized, parallel study. Patients were randomized into two groups: High-EMST and Low-EMST groups. EMST was used at home 7 days/week, once a day, for 25 breaths, 12 weeks. Respiratory muscle strength was measured using a mouth pressure device. Disease severity (Apnea–Hypopnea Index [AHI]) and, respiratory sleep events by polysomnography, total oxidant level(TOS), total antioxidant level(TAS), oxidative stress index (OSI), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels by blood serum were evaluated. Results The percentage of AHI change in the high-EMST group(50.8%) was significantly higher than in the low-EMST group(6.3%; p = .002, d = 1.31). In general, as MEP increased by one unit, AHI decreased by 0.149 points (b = −0.149; CR = −3.065; p = .002), and as AHI increased by one unit, ODI increased by 0.746 points (b = 0.746; CR = 10.604; p &amp;lt; .001). TOS, OSI, TNF-α and IL-6 levels decreased at similar rates in both groups. Conclusions EMST significantly reduces systemic inflammation and oxidative stress while improving expiratory muscle strength in male patients with moderate OSAS. High-EMST is more effective in enhancing the severity of disease than low-EMST. EMST is a practical, effective, and promising treatment for pulmonary rehabilitation in patients with moderate OSAS. Clinical Trials Effect of EMST systemic inflammation and oxidative stress in patients with moderate OSAS, https://clinicaltrials.gov/study/NCT05242406, with the number NCT05242406.

Glial swip-10 controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson's disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease that targets pre-mRNA of replication-dependent histones, proteins recently found in yeast to reduce Cu(II) to Cu(I), and when mutated disrupt ATP production, elevates oxidative stress, and severely impacts cell growth. Whether this process supports neuronal and/or systemic physiology in higher eukaryotes is unknown. Previously, we identified swip-10, the putative Caenorhabditis elegans ortholog of MBLAC1, establishing a role for glial swip-10 in limiting dopamine (DA) neuron excitability and sustaining DA neuron viability. Here, we provide evidence from computational modeling that SWIP-10 protein structure mirrors that of MBLAC1 and locates a loss of function coding mutation at a site expected to disrupt histone RNA hydrolysis. Moreover, we find through genetic, biochemical, and pharmacological studies that deletion of swip-10 in worms negatively impacts systemic Cu(I) levels, leading to deficits in mitochondrial respiration and ATP production, increased oxidative stress, and neurodegeneration. These phenotypes can be offset in swip-10 mutants by the Cu(I) enhancing molecule elesclomol and through glial expression of wildtype swip-10. Together, these studies reveal a glial-expressed pathway that supports systemic mitochondrial function and neuronal health via regulation of Cu(I) homeostasis, a mechanism that may lend itself to therapeutic strategies to treat devastating neurodegenerative diseases.

Relationship between oxidative balance score and prostate cancer: a cross-sectional study of NHANES, 1999–2010

ObjectiveFew studies have examined the relationship between systemic oxidative stress and prostate cancer (PCa) risk. This study aimed to explore potential correlations between PCa and oxidative balance score (OBS), which...