Oxidative Stress Production Research Articles

A computational model of the crosstalk between hepatocyte fatty acid metabolism and oxidative stress highlights the key enzymes, metabolites, and detoxification pathways in the context of MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as NAFLD) is a common liver disease worldwide and carries the risk of progressing to severe liver conditions, such as fibrosis and liver cancer. In the context of MASLD, evaluating fat accumulation in the liver and the subsequent production of oxidative stress is essential to understand the disease propagation. However, clinical studies using human patients to investigate the fat accumulation and the onset of oxidative stress in MASLD face ethical and technical challenges, highlighting the importance of alternative methods. To understand the relationship between fatty acid metabolism, lipid accumulation, oxidative stress generation, and antioxidant mechanisms in hepatocytes, we proposed a new mathematical model. The importance of this model lies in its ability to track the time-dependent changes in oxidative stress and glutathione concentration in response to the input of fatty acids. Furthermore, the model allows for the evaluation of the effects of altering the activity of the key enzymes involved in those mechanisms. Our model is anticipated to provide new insights into MASLD therapy strategies by identifying key pathways and predicting the effects of drug-induced changes in enzyme activity.

Synthesis and Structural Characterization of SiO2 Nanoparticles Using Extract of Gracilaria Crassa Via Green Chemistry Approach.

Biologically synthesized nanoparticles via biological entities are produced with less negative impact on the environment and without expensive chemicals, which have biocompatibility and are eco-friendly. Gracilaria crassa is a well-known marine red alga that is edible and unique and is the commercial source of agar and agarose production. In this work, Gracilaria crassa-mediated SiO2 NPs were synthesized by the green synthesis method. In order to characterize the physicochemical properties of the synthesized SiO2 NPs, a variety of microscopic and spectroscopic approaches were used, including imaging with Field emission scanning electron microscopy, Energy-dispersive X-ray analysis, UV spectrophotometry, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, Zeta potential, and Thermo gravimetric analysis. These results shown that Gracilaria crassa-mediated SiO2 NPs were amorphous nature, negatively charged -15.5 mV and spherical shape in size of 20-50 nm. The antioxidant capacity of synthesised SiO2 NPs was examined by 2,2-Diphenyl-1-picrylhydrazyl assay and it observed as IC50 value of 49.4 μg/mL denotes that could counteract the production of free radicals and oxidative stress. The characteristics of the synthesized Gracilara crassa-mediated SiO2 NPs suggest their application as potential antioxidant agents.

Neuroprotective Role of Zingerone: Investigating the Effective Doses of Zingerone in Lead Acetate-Induced Brain Dysfunctions in Rats

This experiment was designed to determine the effective dose of zingerone against the sublethal dose of lead acetate that induced brain dysfunctions in rats through using different successive doses of zingerone on some parameters related to oxidative stress for 28 days. Thirty-six adult male rats were randomly selected and divided equally into six experimental groups and treated for 28 days as follows: Control group: administered (orally) sterile distilled water. G1 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 25mg/kg for 4 weeks, the rats were then dissected. G2 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 50mg/kg for 4 weeks, the rats were then dissected. G3 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 100mg/kg for 4 weeks, the rats were then dissected. G4 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 150mg/kg for 4 weeks, the rats were then dissected. G5 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 200mg/kg for 4 weeks, the rats were then dissected. Blood samples were collected, by heart punched under anesthesia, at the end of the experiment for measuring the serum malondialdehyde, neuroglobulin, and dopamine concentrations. The result showed a significant (P<0.05) positive correlation between successive doses of zingerone and dopamine and neuroglobulin concentrations, while a significant (P<0.05) negative correlation between successive doses of zingerone and the concentration of malondialdehyde in all animals that are treated with lead acetate compared to the control group. Concluded from this research show that the zingerone has potent antioxidants and neuroprotective effects at the dose 125 mg/kg BW may result in a significant improvement of the neurotransmitter levels and decrease in the production of oxidative stress to the brain tissue.

Hypothyroidism modulates mitochondrial dynamics and mitophagy in the heart of rats under fed and fasting conditions

AimsInvestigate the impact of hypothyroidism on mitochondrial dynamics and mitophagy in the heart under fed and fasting conditions. MethodsHypothyroidism was induced in male Wistar rats with methimazole (0.03 %) for 21 days. Half of the euthyroid and hypothyroid groups underwent a 48-h fasting. Mitochondrial number and ultrastructure were evaluated by transmission electron microscopy. Fusion, fission, mitophagy, oxidative stress, and mitochondrial oxidative phosphorylation system (OXPHOS) components were analyzed by Western Blot and qPCR. ResultsHypothyroidism increased DRP1 activation and the p-DRP1/OPA1 ratio, indicating a shift toward mitochondrial fission over fusion. Under fasting, hypothyroidism prevented the increases in mitochondrial size, elongation, OPA1, and OXPHOS seen in euthyroid fasted rats. Hypothyroidism also raised 4-HNE content, an oxidative stress product, increased mitochondrial injury, and exacerbated fasting-related mitochondrial damage. This was accompanied by elevated Parkin levels in both fed and fasted hypothyroid groups, but without changes in PINK1 levels or Parkin activation. While fasting upregulated Bnip3l and Map1lc3b expression in euthyroid rats, hypothyroidism suppressed this response, though it did not prevent fasting-induced Bnip3 increases. ConclusionsHypothyroidism increases the activation of mitochondrial fission machinery and oxidative stress, and induces mitochondrial damage without activation of mitophagy proteins, suggesting disrupted mitophagy signaling. It also interferes with fasting-induced mitochondrial dynamics adaptations, highlighting the essential role of thyroid hormones in metabolic adaptation to fasting.

Compound 7 regulates microglia polarization and attenuates radiation-induced myelopathy via the Nrf2 signaling pathway in vivo and in vitro studies

BackgroundRadiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) is a newly identified, potent, and selective inhibitor of the Keap1-Nrf2 interaction. This study aimed to explore the protective effects and mechanisms of C7 on RM in vitro and in vivo.MethodsWestern blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) and mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, and tissue staining were employed to explore the protective effects and underlying mechanisms of C7 in radiation-induced primary rat microglia and BV2 cells, as well as RM rat models.ResultsIn this study, we found that C7 inhibited the production of pro-inflammation cytokines and oxidative stress induced by irradiation in vitro. Further, the data revealed that radiation worsened the locomotor functions in rats, and C7 significantly improved histological and functional recovery in RM rats. Mechanically, C7 activated Nrf2 signaling and promoted the microglia transformation from M1 to M2 phenotype.ConclusionC7 could ameliorate RM by boosting Nrf2 signaling and promoting M2 phenotype microglia polarization in vitro and in vivo.

Demyelination in cuprizone mice is ameliorated by calycosin mediated through astrocyte Nrf2 signaling pathway

Oxidative stress plays a pivotal role in multiple sclerosis (MS), triggering demyelination predominantly through excessive peroxide production and the depletion of antioxidants. The accumulation of oxidative damage can be caused by dysregulation of astrocytes, which are the brain's main regulators of oxidative homeostasis. Calycosin, an essential bioactive component extracted from Astragalus, is recognized for its neuroprotective properties. Although recent research has highlighted calycosin's neuroprotective capabilities, its role in demyelinating conditions like MS remains unclear. In this work, we examined the possible molecular mechanism of calycosin's neuroprotective effect on cuprizone (CPZ)-induced demylination in mice. According to our research, calycosin successfully reduced demyelination and behavioral dysfuction in CPZ mice. Calycosin also decreased the production of oxidative stress and enhanced the expression of antioxidants in CPZ mice and in astrocytes induced by hydrogen peroxide (H2O2). Furthermore, both in vivo and in vitro experiments demonstrated that calycosin promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) along with the upregulation of heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase (SOD). Importantly, the application of all-trans retinoic acid (ATRA), a specific inhibitor of Nrf2, effectively reversed the myelin-protective and antioxidant effects conferred by calycosin. This study suggested that calycosin might exert neuroprotection by inhibiting oxidative stress and reducing demyelination via the activation of astrocyte Nrf2 signaling. These findings indicated that calycosin might be a potential candidate for treating MS.

The association of combined GSTM1, GSTT1, and GSTP1 genetic polymorphisms with lung cancer risk in male Iraqi Waterpipe Tobacco (Nargila) smokers

Mutations in genes encoding proteins necessary for detoxifying oxidative stress products have been predicted to increase susceptibility to lung cancer (LC). Despite this, the association between waterpipe tobacco smoking (WP), genetic polymorphisms, and LC risk remains poorly understood. This is the first study to explore the relationship between WP tobacco smoking and these genetic factors. Previously, we investigated the association of GSTP1 SNPs (rs1695-A/G and rs1138272-C/T) with LC in Iraqi males who smoke WP. Here, we expanded our analysis to include GSTM1 (active/null) and GSTT1 (active/null) genotypes, both individually and in combination with GSTP1 SNPs. Multiplex PCR and RFLP-PCR assays were utilized to determine the genotypes of 123 cases and 129 controls. No significant association was observed between GSTM1-null or GSTT1-null genotypes and LC risk, either separately or in combination with variant genotypes of GSTP1 (rs1695 "AG+GG" and rs1138272 "CT+TT"). However, smoking WP and carrying null genotypes elevated the risk five-fold for GSTM1-null (OR 5.17, 95 % CI 2.02–13.24, P<0.001) and three-fold for GSTT1-null (OR 3.08, 95 % CI 1.55–6.13, P=0.001) compared to non-smokers carrying active genotypes. Conversely, genotype distribution analysis based on LC histological types did not indicate an increased risk of LC. Lung cancer is a complex multifactorial disease. WP smoking and GSTs genetic polymorphisms might be associated with an increased risk of developing LC. However, our data did not confirm an association between GST polymorphisms alone and the risk of LC.

Research Progress on Mechanism of Chinese Medicine Intervention on Cuprotosis Induced Apoptosis of Tumor Cells

In the current field of cancer treatment, the search for new therapeutic targets and methods remains a focal area of research. Traditional Chinese medicine contains a variety of pharmacologically active components that interact with multiple targets and signaling pathways in the human body, demonstrating potential anti-tumor effects. Copper plays a crucial role in various physiological processes; its homeostasis is tightly regulated to limit the production of oxidative stress and toxicity, and it intervenes in the processes of tumor development, metastasis, and recurrence. Cuproptosis represents a novel form of copper-dependent cell death that differs from previously known regulatory cell death mechanisms, offering a fresh perspective on the link between copper homeostasis and mitochondrial metabolism. Targeting copper has emerged as a new anti-cancer strategy. Current research on the intervention of cuproptosis by TCM is limited; leveraging the advantages of TCM's multi-target, multi-pathway approach could further elucidate the mechanisms of cuproptosis, bringing more possibilities to cancer treatment modalities.

Natural Product Interventions in Peripheral Diabetic Neuropathy: A Multi-Target Approach

Peripheral diabetic neuropathy (PDN) is a well-known impediment of diabetes mellitus. That is one of the common kinds of neuropathy, categorized by reduced neuronal function in the minor limbs including excruciating neurological pain. A medical examination is used to subclassify asymmetric and symmetric neuropathy. Diabetes is associated with several pathways, one of which is the activation of the polyol route, the production of oxidative stress, poly ADP-ribose polymerase, the formation of advanced glycation outputs, and the pathways of hexosamine. Although there are a few symptomatic and supportive treatments in use, like antiarrhythmics, tricyclic medications, aldose reductase, opioid analgesics, protein kinase C inhibitors, and incretin the results are unimpressive. To bridge this space, herbal product-based treatment can be a very successful replacement. This narrative review tries to understand the research currently accessible on the function of different biological entities in the treatment of PDN. These chemicals are essential for lowering aldose reductase activity, oxidative-nitrosative stress, and neuronal death. They improve axonal regeneration, nerve transmission velocity, as well as antioxidant molecules while controlling glucose and HbA1c%. (Malondialdehyde, catalase, superoxide dismutase). They are renowned for their ability to reduce heat and mechanical hyperalgesia as well as tactile allodynia. Thus, these substances need to have their animal study and clinical efficiency assessed. Natural compounds may be auspicious participants in the fight against PDN that provide a glimpse of optimism to those in need.

PM2.5 Exposure Aggravates Inflammatory Response and Mucus Production in 16HBE Cells through Inducing Oxidative Stress and RAGE Expression.

Particulate matter 2.5 (PM2.5)-induced oxidative stress has been extensively proposed as a pivotal event in lung diseases. Receptor for advanced glycation end-products (RAGE) is a receptor of pro-inflammatory ligands that has been supported to be implied in the progression of multiple lung diseases. This study attempts to delineate the specific effects of PM2.5 on human bronchial epithelial 16HBE cells in vitro and figure out whether PM2.5 functions via mediating oxidative stress and RAGE. In PM2.5-challenged 16HBE cells, MTT assay detected cell viability. ELISA estimated inflammatory levels. Flow cytometry analysis measured ROS activity and related assay kits examined oxidative stress levels. Western blot tested nuclear factor E2-related factor 2 (Nrf2), RAGE, β-catenin, and mucin 5AC (MUC5AC) expression. Immunofluorescence staining evaluated nuclear translocation of β-catenin. It was noticed that PM2.5 exposure exacerbated inflammatory response, oxidative stress, and mucus production. Additionally, PM2.5 elevated RAGE expression while declined Nrf2 expression as well as stimulated the nuclear translocation of β-catenin. Furthermore, RAGE inhibition or nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor VAS2870 mitigated inflammatory response, oxidative stress, and mucus generation in PM2.5-exposed 16HBE cells. In addition, RAGE inhibition or VAS2870 raised Nrf2 expression, reduced RAGE expression, and hampered β-catenin nuclear translocation. Briefly, PM2.5 might act as a leading driver of inflammatory response and mucus production in lung injury, the mechanism of which might be related to the activation of oxidative stress and the up-regulation of RAGE.

PSVI-14 Effects of poor maternal nutrition during gestation on first generation offspring oxidative status in skeletal muscle

Abstract Poor maternal nutrition (restricted- and over-nutrition) during gestation negatively impacts offspring pre- and post-natal growth. Previous work has identified decreased muscle mass and increased adiposity, leading to poor quantity and quality of animal protein products. Alterations in oxidative status, such as the imbalance of antioxidant activity and the production of free radicals, can result in oxidative stress damaging lipid membranes, proteins, and DNA. Changes in oxidative status may contribute to the poor growth outcomes observed in offspring from poorly nourished dams. Therefore, the objective of this research was to determine the effects of poor maternal nutrition during gestation on the oxidative status in offspring skeletal muscle in sheep. We hypothesized that offspring of restricted- and over-fed ewes would have decreased antioxidant activity and increased products of oxidative stress in skeletal muscle. To test this hypothesis, multiparous Dorset ewes (n = 46) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of total nutrient requirements (NRC) from d 30 of gestation until parturition. Following parturition, ewes were fed a control diet throughout lactation. At d 282 of age semitendinosus (STN) samples were collected from rams at necropsy, and at d 284 of age muscle biopsies from STN were collected from ewes. Data were analyzed in SAS using PROC MIXED with fixed effects of maternal diet and offspring sex. Data were considered significant at P ≤ 0.05. The activity of the endogenous antioxidant superoxide dismutase (SOD) was decreased by 45% and 33% in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). Offspring sex did not alter STN SOD activity (P = 0.35). Muscle glutathione peroxidase (GPx) activity was decreased in RES offspring by 20% compared with CON (P ≤ 0.04), but neither differed from OVER offspring (P ≥ 0.24). Ewes had 34% greater GPx activity compared with rams (P &amp;lt; 0.0001). Offspring from RES and OVER ewes had 77% and 87% greater concentrations of malondialdehyde (MDA), a marker of lipid peroxidation, when compared with CON (P &amp;lt; 0.0001). Ewes had 29% greater MDA concentrations compared with rams (P = 0.05). Protein carbonyl (PC), a marker of protein oxidation, concentrations were 36% and 38% greater in RES and OVER offspring, respectively, compared with CON (P ≤ 0.01). The decrease in antioxidant activities and increase in products of protein and lipid oxidation in offspring from poorly nourished dams suggests dysregulation in skeletal muscle oxidative status that may contribute to the negative consequences observed in offspring. Future work should focus on determining the mechanistic role of skeletal muscle oxidative stress in the decreased quantity and quality of animal protein products and identifying potential strategies to mitigate alterations in oxidative status as a result of poor maternal nutrition during gestation.

Antifouling activity and ecotoxicological profile of the cyanobacterial oxadiazine nocuolin A

Pursuing effective and biocompatible natural compounds to supplant current biocidal antifouling (AF) technologies remains crucial and challenging. Among natural products hosts, cyanobacteria are recognized as producers of bioactive secondary metabolites that are underexplored in terms of anti-biofilm and AF potential. Nocuolin A, a natural oxadiazine previously isolated and known to be produced by different cyanobacterial strains, has demonstrated bioactive potential, particularly against tumor cell lines. Considering this potential and its exquisite chemical structure, here nocuolin A was investigated as a potential natural AF agent through an integrative approach including AF bioactivity testing across distinct levels of biological organization, mode of action assessment, ecotoxicity evaluation, and ecological risk predictions. Nocuolin A was found to inhibit the settlement of mussel (Mytilus galloprovincialis) plantigrades (EC50 = 3.905 μM) while showing no toxicity to this biofouling species (LC50 > 100 μM). Additionally, while exhibiting no inhibitory activity against the growth of five marine biofilm-forming bacterial strains, it significantly suppressed the growth of the marine biofilm-forming diatom Navicula sp. (EC50 = 1.561 μM), and had a lethal effect on this diatom species (>3.1 μM). The AF targets of nocuolin A on mussel plantigrades revealed no correlation with acetylcholinesterase and tyrosinase metabolic processes; however, proteins involved in oxidative stress, muscle regulation, and energy production were highlighted. The results also provide insights into the ecological risk of nocuolin A, including its ecotoxicity against Artemia salina nauplii (LC50 = 2.480 μM), Amphibalanus amphitrite nauplii (LC50 = 0.0162 μM), and Danio rerio embryos (LC50 = 0.0584 μM). When matching these results with simulated environmental values, nocuolin A was deemed a considerable threat to the ecosystems. While this research highlights the AF activity of nocuolin A, it also emphasizes the potential adverse environmental impact when applied in preventive coatings.

Anti-Oxidant and Anti-Bacterial Behavior of Sodium Alginate Patches Fortified with Polyurethane and Ag-MOF as Potential Future Wound Healing Material

ABSTRACT Sodium Alginate (SA) is a natural polysaccharide with a high degree of biocompatibility, biodegradability, water absorption properties and stiffness. The inherent brittleness of SA limits its applications in the field of wound healing. The blending of highly flexible polyurethane (PU) with SA could alter the nature of film. In addition, the incorporation of Ag-Metal Organic Framework (Ag-MOF) synthesized via the solvothermal method can help in the enhancement of stability and biological characteristics. The SA and its composite films were obtained through a feasible phase inversion technique. In addition, the Ag-MOF@SA/PU film demonstrates the strongest bacteriostatic impact on E. faecalis and P. aeruginosa, with percentages of approximately 96.9% and 96.41%, respectively. Furthermore, the film demonstrates a radical scavenging efficiency of 83.96%. Moreover, the Ag-MOF@SA/PU film exhibited a significant increase in the production of oxidative stress, attaining a value of 84.89%. Owing to the results, Ag-MOF@SA/PU was taken for in-vitro degradability analysis and visible surface erosion was observed over time. Thus, the Ag-MOF@SA/PU film could be considered for future wound healing therapy.

Effect of allyl isothiocyanate on 4-HNE induced glucocorticoid resistance in COPD and the underlying mechanism

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition, and its clinical management primarily targets bronchodilation and anti-inflammatory therapy. However, these treatments often fail to directly address the progression of COPD, particularly its associated glucocorticoid (GC) resistance. This study elucidates the mechanisms underlying GC resistance in COPD and explores the therapeutic potential of allyl isothiocyanate (AITC) in modulating MRP1 transport. We assessed the levels of the oxidative stress product 4-HNE, HDAC2 protein, inflammatory markers, and pulmonary function indices using animal and cell models of GC-resistant COPD. The cascade effects of these factors were investigated through interventions involving AITC, protein inhibitors, and dexamethasone (DEX). Cigarette smoke-induced oxidative stress in COPD leads to the accumulation of the lipid peroxidation product 4-HNE, which impairs HDAC2 protein activity and diminishes GC-mediated anti-inflammatory sensitivity due to disrupted histone deacetylation. AITC regulates MRP1, facilitating the effective efflux of 4-HNE from cells, thereby reducing HDAC2 protein degradation and restoring dexamethasone sensitivity in COPD. These findings elucidate the mechanism of smoking-induced GC resistance in COPD and highlight MRP1 as a potential therapeutic target, as well as the enormous potential of AITC for combined GC therapy in COPD, promoting their clinical applications.

Protective Effects of Spermacoce hispida Against Cisplatin-Induced Nephrotoxicity: A Study on Oxidative and Nitrosative Stress

Background: Nephrotoxicity is a common and severe side effect of cisplatin, a widely used chemotherapeutic agent. The mechanism of cisplatin-induced nephrotoxicity involves oxidative stress, inflammation, and apoptosis, leading to renal damage. There is growing interest in exploring natural products with antioxidant and anti-inflammatory properties as potential protective agents against drug-induced nephrotoxicity.Objective: The present study aimed to investigate the protective effects of Spermacoce hispida against cisplatin-induced nephrotoxicity in an in vivo rat model. Methods: S. hispida was collected, and plant extracts were prepared using different solvents. The prepared extracts underwent phytochemical screening. Nephrotoxicity was induced in rats through a single intraperitoneal injection of cisplatin at a dose of 5 mg/kg. S. hispida extracts at a dose of 100 mg/kg were administered to assess their protective activity. Key parameters measured included blood urea nitrogen (BUN), serum creatinine, oxidative stress markers, proinflammatory cytokines, nitric oxide (NO) levels, and histological alterations in kidney tissue.Results: Cisplatin treatment resulted in increased levels of BUN, serum creatinine, and proinflammatory cytokines in rats, indicating nephrotoxicity. However, treatment with S. hispida extracts for 14 days significantly decreased these elevated levels. Additionally, S. hispida treatment reduced oxidative stress and NO production in cisplatin-treated rats. Histological examination revealed that cisplatin induced structural damage in kidney tissues, which was normalized by S. hispida treatment. Conclusion: The study concludes that Spermacoce hispida exhibits nephroprotective activity, likely by inhibiting oxidative stress and NO production, thereby mitigating cisplatin-induced nephrotoxicity in rats

Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS)

BackgroundPolycystic ovary syndrome (PCOS) presents a significant challenge in women’s reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulosa cells, whose dysfunction contributes to aberrant steroid hormone production and oxidative stress. Mitochondrial dysfunction emerges as a key player, influencing cellular energetics, oxidative stress, and steroidogenesis. This study investigates the therapeutic potential of menstrual blood-derived stem cells (MenSCs) and their exosomes in mitigating mitochondrial dysfunction and oxidative stress in PCOS granulosa cells.MethodsUsing a rat model of PCOS induced by letrozole, granulosa cells were harvested and cultured. MenSCs and their exosomes were employed to assess their effects on mitochondrial biogenesis, oxidative stress, and estrogen production in PCOS granulosa cells.ResultsResults showed diminished mitochondrial biogenesis and increased oxidative stress in PCOS granulosa cells, alongside reduced estrogen production. Treatment with MenSCs and their exosomes demonstrated significant improvements in mitochondrial biogenesis, oxidative stress levels, and estrogen production in PCOS granulosa cells. Further analysis showed MenSCs' superior efficacy over exosomes, attributed to their sustained secretion of bioactive factors. Mechanistically, MenSCs and exosomes activated pathways related to mitochondrial biogenesis and antioxidative defense, highlighting their therapeutic potential for PCOS.ConclusionsThis study offers insights into granulosa cells mitochondria’s role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

CD8+ T-cell deficiency protects mice from abdominal aortic aneurysm formation in response to calcium chloride2.

Abdominal aortic aneurysm (AAA) is an aneurysm-like dilated and highly fatal cardiovascular disease. CD8+ T cells have been shown to be critical for vascular pathological processes, but the contribution of these lymphocytes to vascular diseases remains elusive. Eight-week-old male wildtype (CD8+/+) and Cd8a knockout (CD8-/-) mice were used in a calcium chloride2 (CaCl2)-induced experimental AAA model. At 6 weeks after surgery, CD8+ T-cell deletion prevented the formation of AAA, accompanied by reductions of the levels of inflammatory (interferon-γ [IFN-γ], interleukin-1β, monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, NOD-like receptor protein 3, caspase-1), oxidative stress [NADPH oxidase and gp91phox], and proteolysis (cathepsin S, cathepsin K, matrix metalloproteinase-2 [MMP-2] and MMP-9) proteins and/or genes in plasma and/or AAA tissues. Immunoreactivities of MMP-2 and MMP-9 were observed in macrophages. An injection of IFN-γ and adoptive transfer of CD8+ T cells of IFN-γ+/+ mice diminished CD8-/--mediated vasculoprotective actions in the AAA mice. In vitro, IFN-γ enhanced MMP-2 and MMP-9 gelatinolytic activities in macrophage and/or vascular smooth muscle cells. The vasculoprotective effects of CD8+ T-cell deletion in a mouse CaCl2-induced AAA model were likely attributable to, at least in part, the attenuation of IFN-γ-dependent inflammation action, oxidative stress production, and proteolysis, suggesting a novel therapeutic target for AAA formation by regulating CD8+ T-cell-derived IFN-γ secretion.

Nigella sativa L. and its bioactive and nutraceutical components in the management of diabetic peripheral neuropathy.

Diabetes-induced hyperglycemia leads to excessive production of oxygen free radicals, inflammatory cytokines, and oxidative stress, which initiates diabetic peripheral neuropathy(DPN). Currently, this condition affects 20% of adults with diabetes. Despite significant advances in the treatment of diabetes, the incidence of its complications, including DPN, is still high. Thus, there is a growing research interest in developing more effective and treatment approaches with less side effects for diabetes and its complications. Nigella sativa L. (NS) has received much research attention as an antioxidant, anti-yperglycemic factor, and anti-inflammatory agent. This natural compound demonstrates its antidiabetic neuropathy effect through various pathways, including the reduction of lipid peroxidation, the enhancement of catalase and superoxide dismutase enzyme activity, and the decrease in inflammatory cytokine levels. The present review focuses on the bioactive and nutraceutical components of black cumin (Nigella sativa L.) and their effects on DPN. In addition, we have also summarized the findings obtained from several experimental and clinical studies regarding the antidiabetic neuropathy effect of NS in animal models and human subjects.

Influence of humic acids on growth performance, bravery, stress resistance, antioxidant activity, and immune gene expression in male Siamese fighting fish (Betta splendens)

The current study investigated the effects of a humic acid supplement on the growth performance, antioxidant enzyme activity, immune-related genes, behavior and endocrinology of male Betta splendens fish. Fish species that are naturally exposed to high levels of humic substances in their environment are likely to perform better under captive conditions when given these substances. In this study, fish were fed a diet containing 0, 0.5 %, 1 %, and 1.5 % humic acid for six weeks. The results showed no significant differences in growth and feeding parameters between treatments (p > 0.05). The fish with a diet of 1.5 % humic acid showed more aggressive behavior in the mirror test than the control group (p < 0.05). In contrast, the fish fed a diet containing 1 % and 1.5 % humic acid showed a higher level of activity in the test with new objects than the control group (p < 0.05). The testosterone levels after aggression were significantly higher in the fish fed diets containing 1 % and 1.5 % humic acid than in the control group (p < 0.05). In addition, the humic acid-treated fish showed lower oxidative stress and cortisol production in common aquaculture stressors than the control (p < 0.05). Gene expression analysis showed upregulation of immune-related genes, including β-defensin 1, c-type lysozyme, interleukin-1β, and tumor necrosis factor-α, in response to humic acid supplementation compared to control (p < 0.05). Overall, the results of this study indicate that a diet containing 1 % humic acid has a positive effect on the physiology, immunology, and behavior of male B. splendens.

Ginkgo biloba extract inhibits hippocampal neuronal injury caused by mitochondrial oxidative stress in a rat model of Alzheimer's disease.

Ginkgo biloba extracts (GBE) have been shown to effectively improve cognitive function in patients with Alzheimer's disease (AD). One potential therapeutic strategy for AD is to prevent loss of adult hippocampal neurons. While recent studies have reported that GBE protects against oxidative stress in neurons, the underlying mechanisms remain unclear. In this study, an AD-like rat model was established via bidirectional injection of amyloid beta 25-35 (Aβ25-35; 20 μg) in the hippocampal CA1 region. Learning and memory abilities of experimental rats were AD assessed in response to oral administration of 7.5 g/L or 15 g/L Ginkgo biloba extract 50 (GBE50) solution and the peroxidation phenomenon of hippocampal mitochondria determined via analysis of mitochondrial H2O2 and several related enzymes. Levels of the oxidative stress-related signaling factor cytochrome C (Cyto C), apoptosis-related proteins (Bax, Bcl-2 and caspase-3) and caspase-activated DNase (CAD) were further detected via western blot. 8-Hydroxydeoxyguanosine (8-OHdG), the major product of DNA oxidative stress, was evaluated to analyze DNA status. Our results showed elevated H2O2 levels and monoamine oxidase (MAO) activity, and conversely, a decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus of AD rats. Administration of GBE50 regulated the activities of these three enzymes and induced a decrease in H2O2. GBE50 exerted regulatory effects on abnormally expressed apoptotic proteins in the AD rat hippocampus, enhancing the expression of Bcl-2, inhibiting release of Cyto C from mitochondria, and suppressing the level of caspase-3 (excluding cleaved caspase-3). Furthermore, GBE50 inhibited DNA damage by lowering the generation of 8-OHdG rather than influencing expression of CAD. The collective findings support a protective role of GBE50 in hippocampal neurons of AD-like animals against mitochondrial oxidative stress.