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BACKGROUND: Parkinson’s disease is a neurodegenerative disease, and its pathogenesis involves mitochondrial dysfunction. Exercise has a potential ameliorative effect on mitochondrial dysfunction related to Parkinson’s disease, but there is no comprehensive review and in-depth analysis in this field. OBJECTIVE: To comprehensively review and analyze mitochondrial dysfunction related to Parkinson’s disease and the potential ameliorative effect of exercise, thereby providing new ideas and methods for the treatment and prevention of Parkinson’s disease. METHODS: We searched the Web of Science, PubMed, CNKI, WanFang, and VIP databases with the keywords of “mitochondria, mitochondrial function, mitochondrial disease, mitochondrial dysfunction, Parkinson’s disease, Parkinson, exercise, physical activity, exercise training, exercise therapy, mitochondrial impairment, mitochondrial damage, mitochondrial defects” in Chinese and “mitochondria, Parkinson’s disease, Parkinson disease, physical exercise, exercise, physical activity, mitochondrial dysfunction, mitochondrial damage, mitochondrial impairment, athletic training, exercise training, rehabilitation” in English. A total of 89 articles were included for review and analysis. RESLUTS AND CONCLUSION: Parkinson’s disease is closely related to mitochondrial dysfunction, including mitochondrial biogenesis inhibition, reduced autophagy, increased apoptosis, abnormal elevation of Ca2+ concentration, and increased oxidative stress in Parkinson’s disease patients. Exercise has a positive effect on mitochondrial dysfunction related to Parkinson’s disease, by promoting mitochondrial biogenesisand autophagy, regulating mitochondrial morphology, altering the plasticity of the mitochondrial respiratory chain, and reducing oxidative stress, thus helping to improve the development and progression of Parkinson’s disease. However, the detailed mechanism between mitochondrial dysfunction and the ameliorative effect of exercise is still not fully understood, and future clinical studies can be conducted to validate the results of animal models and gain insights into the benefits and mechanisms of exercise in patients with Parkinson’s disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vitamin C, as an essential nutrient, has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia. Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia. OBJECTIVE: To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia, and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence. METHODS: The first author performed a computer search of PubMed, Web of Science, CNKI and other databases for relevant studies involving vitamin C in sarcopenia. The search keywords were “vitamin C, ascorbic acid, L-ascorbic acid, ascorbate, antioxidants, oxidative stress, sarcopenia, muscular atrophy, muscle weakness, muscle development, skeletal muscle regenerate, muscles, skeletal muscle” in English and Chinese, respectively. The search period was from each database inception to July 2023. After screening, 85 articles were included for further review. RESULTS AND CONCLUSION: Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia. In addition, vitamin C supplementation is also useful for improving skeletal muscle mass, strength and physical function with potential synergistic effects in exercise strategies for sarcopenia. The effects of vitamin C on sarcopenia may be via the following biological mechanisms: vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle, thus positively regulating protein metabolic homeostasis, and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function. In addition, vitamin C affects myoblast proliferation, differentiation and myotube size, mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways, which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue. The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors, such as the choice of supplementation dose and duration, the design of exercise prescription when vitamin C is combined with an exercise intervention, and the assessment of the redox status of the individual. It is recommended that future studies should be conducted in older patients with sarcopenia (< 50 μmol/L) with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1 000 mg/d vitamin C (for 6 months or longer) with at least two or more types of multi-type combined exercise, with supplementation timed to take place at 1 hour after the end of the exercise, and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored. In conclusion, the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more, while the appropriate design of exercise prescriptions (especially the type and intensity of exercise) needs to be further determined. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) including the superoxide anion (O2•−) are typically studied in cell cultures using fluorescent dyes, which provide only discrete single-point measurements. These methods lack the capabilities for assessing O2•− kinetics and release in a quantitative manner over long monitoring times. Herein, we present the fabrication and application of an electrochemical biosensor that enables real-time continuous monitoring of O2•− release in cell cultures for extended periods (> 8 h) using an O2•− specific microelectrode. To achieve the sensitivity and selectivity requirements for cellular sensing, we developed a biohybrid system consisting of superoxide dismutase (SOD) and Ti3C2Tx MXenes, deposited on a gold microwire electrode (AuME) as O2•− specific materials with catalytic amplification through the synergistic action of the enzyme and the biomimetic MXenes-based structure. The biosensor demonstrated a sensitivity of 18.35 nA/μM with a linear range from 147 to 930 nM in a cell culture medium. To demonstrate its robustness and practicality, we applied the biosensor to monitor O2•− levels in human leukemia monocytic THP-1 cells upon stimulation with lipopolysaccharide (LPS). Using this strategy, we successfully monitored LPS-induced O2•− in THP-1 cells, as well as the quenching effect induced by the ROS scavenger N-acetyl-l-cysteine (NAC). The biosensor is generally useful for exploring the role of oxidative stress and longitudinally monitoring O2•− release in cell cultures, enabling studies of biochemical processes and associated oxidative stress mechanisms in cellular and other biological environments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that hesperetin exerts protective effects on chondrocytes through a variety of mechanisms or signaling pathways, but the protective mechanisms have not been fully elucidated. OBJECTIVE: To investigate the effect of hesperetin on lipopolysaccharide-induced inflammatory degeneration of chondrocytes. METHODS: Knee joint chondrocytes from suckling Sprague-Dawley rats were isolated and cultured in vitro, and identified by Safranine O staining. The cytotoxicity of hesperetin on chondrocytes was determined by the MTT assay to ensure the optimal concentration of hesperetin. Chondrocytes were randomly divided into three groups, including the control group, model group, and experimental group. The cellular model of osteoarthritis was established in the latter two groups by simulating chondrocytes with lipopolysaccharide. Chondrocytes in the experimental group was then intervened with hesperetin for 24 hours. Calcein-AM/EthD-I staining was used to detect cell viability. Immunohistochemical staining was performed to determine the expression of type II collagen in chondrocytes. Intracellular reactive oxygen species level was detected by a reactive oxygen species detection kit. Total glutathione level was detected by ELISA. Real-time fluorescent PCR was employed to detect the expression of interleukin 1β, interleukin 6, tumor necrosis factor α and type II collagen. RESULTS AND CONCLUSION: Safranine O staining results showed that the cells extracted were chondrocytes. Cytotoxicity test results showed 0.5 μmol/L hesperetin had the most significant effect on chondrocyte vitality. Compared with the control group, the model group showed a decrease in chondrocyte proliferation ability, an increase in reactive oxygen species levels, a decrease in total glutathione levels, an increase in type II collagen degradation, an increase in the levels of interleukin 1β, interleukin 6, and tumor necrosis factor α, and a decrease in the expression of type II collagen (P < 0.05). Compared with the model group, in the experimental group, the proliferation ability of chondrocytes increased, reactive oxygen species levels decreased, total glutathione levels increased, and type II collagen degradation decreased, levels of interleukin 1β, interleukin 6, and tumor necrosis factor α downregulated, and the expression of type II collagen upregulated (P < 0.05). To conclude, hesperetin has a protective effect on lipopolysaccharide-induced inflammatory degeneration of osteoarthritic chondrocytes, and the mechanism may be associated with inhibition of reactive oxygen species-mediated oxidative stress. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that there is a close association between spinal cord injury and ferroptosis, and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE: To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS: Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group, model group and tetramethylpyrazine group, with 12 rats in each group. Animal models of spinal cord injury were established using the modified Allen’s method in the latter two groups. No treatment was given in the sham-operated group, while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution, once a day, for 28 days. RESULTS AND CONCLUSION: The Basso, Beattie & Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the shamoperated group but higher than that in the model group after 14, 21, and 28 days of treatment (P < 0.05). After 28 days of treatment, hematoxylin-eosin staining showed that in the model group, the spinal cord tissue of rats showed cavity formation, necrotic tissue and inflammatory infiltration with fibrous tissue formation; in the tetramethylpyrazine group, the area of spinal cord tissue defects was smaller, and inflammatory infiltration and fibrous tissue formation were less than those in the model group. After 28 days of treatment, Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group, and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group. After 28 days of treatment, the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased (P < 0.05) and the level of malondialdehyde was increased in the model group compared with the sham-operated group (P < 0.05); the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased (P < 0.05) and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group (P < 0.05). After 28 days of treatment, qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4, ferritin heavy chain, and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group (P < 0.05), while the mRNA and protein levels of glutathione peroxidase 4, ferritin heavy chain, and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group (P < 0.05). Immunofluorescence staining showed that after 28 days of treatment, the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group. To conclude, tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) pollution is a serious threat to food safety and human health. Minimization of Cd uptake and enhancing Cd tolerance in plants are vital to improve crop yield and reduce hazardous effects to humans. In this study, we investigate the effect of a synergistic system with phytohormone (24-Epibrassinolide, EBL) and silicon (Si) on Cd toxicity and accumulation of rice plants. The results revealed that Si, EBL and their combination rescued Cd-induced growth inhibition, as evidenced by the increased dry weight of root and shoot. The chlorophyll content and photosynthetic performance were improved. The activity of antioxidant enzymes (SOD, POD and CAT) was increased and oxidative stress was alleviated. More importantly, Cd content in root was decreased by 20.25%, 17.72% and 27.84%, while Cd content in shoot decreased by 21.17%, 16.47% and 25.88%, respectively. Moreover, Si, EBL and Si + EBL treatment enriched cell wall-bound Cd and reduced Cd toxicity to functional organelles. Meanwhile, the residual form of Cd was enriched and the highly toxic forms of Cd (inorganic and water-soluble Cd) were decreased. The joint application showed better effects than applying Si and EBL alone. Collectively, this study provides an effective way for Cd toxicity mitigation in rice plants. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co‐morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia‐induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions. Experimental Approach: The feed‐forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine‐induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches. Key Results: Reserpine‐treated mice developed pain‐like behaviours (mechanical/cold hypersensitivity) and early anxiety‐depressive‐like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine‐induced neuroinflammation (NADPH oxidase 1‐dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia‐like behaviours. Conclusion and Implications: Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine‐evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia‐related behaviours. [ABSTRACT FROM AUTHOR]

Achyrocline satureioides, popularly called "marcela" in Brazil, is used in traditional medicine in South America. A. satureioides, inflorescences are used for many conditions, including to minimize the Sars-Cov-2 symptoms. Therefore, the aim of this study was to determine the toxicity profile of A. satureioides aqueous extract (ASAE), using the Caenorhabditis elegans (C. elegans) alternative model. Survival, reproduction, development, and transgenerational assays were performed. The effects of ASAE were investigated under conditions of thermal stress and presence of oxidant hydrogen peroxide (H2O2). In addition, C. elegans strains containing high antioxidant enzyme levels and elevated lineages of daf-16, skn-1 and daf-2 regulatory pathways were examined. The ASAE LC50 value was found to be 77.3 ± 4 mg/ml. The concentration of ASAE 10 mg/ml (frequently used in humans) did not exhibit a significant reduction in worm survival at either the L1 or L4 stage, after 24 or 72 hr treatment. ASAE did not markedly alter the body area. In N2 strain, ASAE (10 or 25 mg/ml) reversed the damage initiated by H2O2. In addition, ASAE protected the damage produced by H2O2 in strains containing significant levels of sod-3, gst-4 and ctl − 1,2,3, suggesting modulation in these antioxidant systems by this plant extract. ASAE exposure activated daf-16 and skn-1 stress response transcriptional pathways independently of daf-2, even under extreme stress. Data suggest that ASAE, at the concentrations tested in C. elegans, exhibits a reliable toxicity profile, which may contribute to consideration for safe use in humans. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionThe objective of this review is to qualitatively appraise the available literature to evaluate the efficacy of circulatory systemic oxidative stress markers (OSMx) in determining the diagnosis and outcome of TBI.A systematic review was conducted of PubMed/Medline, Embase and Google Scholar databases per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for studies which employed serum or plasma OSMx analysis for diagnostic or prognostic purposes in patients with TBI.Eight studies were included. There were 654 patients across the eight studies, of which 518 (79.2%) patients had sustained a TBI. The heterogeneity between studies in terms of OSMxs analyzed ultimately made collective analysis inappropriate. Nevertheless, several studies highlighted the potential role of circulatory OSMx levels in determining the diagnosis (presence and severity) and prognosis (functional outcome and mortality) of TBI.The care for patients with TBI remains a complex clinical challenge with a high morbidity and mortality profile. Evidenced by this review, circulatory OSMxs appear to have the potential to supplement current diagnostic measures, in addition to identifying new treatment strategies and monitoring recovery. Despite early promise, the evidence for such markers remains in its infancy and robust prospective studies are needed. [ABSTRACT FROM AUTHOR]

• It emphasizes the critical importance of novel therapeutic approaches. • It is the first to discusses the functions of L-cysteine in the anxiety. • It provides an overview of the basic features of L-cysteine. • It presents potential mechanism of L-cysteine in the treatment of anxiety. • It reviews the pathogenesis and neuroanatomical basis of anxiety disorders. Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases. [ABSTRACT FROM AUTHOR]

• Trehalose at concentrations of 0.1–200 mM is safe in SCA3 cell models. • Trehalose decreases the formation of aggregates of mutant ataxin-3. • Trehalose reduces full-length ataxin-3 protein levels. • Trehalose holds therapeutic potential to treat SCA3 likely by its antioxidant activity. Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by mutant ataxin-3 with an abnormally expanded polyQ tract and is the most common dominantly inherited ataxia worldwide. There are no suitable therapeutic options for this disease. Autophagy, a defense mechanism against the toxic effects of aggregation-prone misfolded proteins, has been shown to have beneficial effects on neurodegenerative diseases. Thus, trehalose, which is an autophagy inducer, may have beneficial effects on SCA3. In the present study, we examined the effects of trehalose on an SCA3 cell model. After trehalose treatment, aggregate formation, soluble ataxin-3 protein levels and cell viability were evaluated in HEK293T cells overexpressing ataxin-3-15Q or ataxin-3-77Q. We also explored the mechanism by which trehalose affects autophagy and stress pathways. A filter trap assay showed that trehalose decreased the number of aggregates formed by mutant ataxin-3 containing an expanded polyQ tract. Western blot and Cell Counting Kit-8 (CCK-8) results demonstrated that trehalose also reduced the ataxin-3 protein levels and was safe for ataxin-3-expressing cells, respectively. Western blot and total antioxidant capacity assays suggested that trehalose had great therapeutic potential for treating SCA3, likely through its antioxidant activity. Our data indicate that trehalose plays a neuroprotective role in SCA3 by inhibiting the aggregation and reducing the protein level of ataxin-3, which is also known to protect against oxidative stress. These findings provide a new insight into the possibility of treating SCA3 with trehalose and highlight the importance of inducing autophagy in SCA3. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) of the kidney is responsible for renal regulation and homeostasis, and patients with chronic kidney disease frequently receive RAS blockades. The purpose of this study was to determine the connection between the stimulation of arsenic in rats and changes in transcription levels of RAS hormones, biochemical parameters and antioxidant enzymes. Twenty-five Wistar rats were divided into five groups (control, low, middle, high dose and high dose + α-tocopherol groups) and given oral doses of 8.2, 12.3 and 16.4 mg/kg sodium arsenite (NaAsO2) and 50 mg/kg α-tocopherol for two months. RT-PCR analysis in nephrocytes revealed that mRNA expression of p53, p21, p27, caspases (3, 7 and 9), ACE, AGT, AT1R, CYP1A1 and Bax was found to be upregulated by ~1.9, ~1.6, ~1.5, ~2.3, ~3.3, ~3, ~2, ~1.9, ~2.4, ~1.7 and ~3.3-fold, whereas that of cyclin A, cyclin B1, cyclin E1, CDK 1, CDK 2, Bcl-2, CAT, SOD, GPx, GR and GST was downregulated consistently in renal tissues of arsenic-exposed groups by ~0.6, ~0.5, ~0.4, ~0.5, ~0.6, ~0.5, ~0.6, ~0.4, ~0.6, ~0.5 and ~0.6-fold respectively. The activities of alkaline phosphatase, acid phosphatase and antioxidant enzymes were significantly reduced by 63%, 71%, 40%, 37% and 44% respectively, upon treatment with NaAsO2. Through this study, we can gain knowledge about the potential function of RAS enzymes and antioxidant enzymes against the detrimental effects of arsenic-induced oxidative stress due to altered transcription levels of RAS enzymes in Wistar rats. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations. Results: We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins. Conclusions: These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). Methods: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. Results: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). Conclusion: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. Trial registration: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020. [ABSTRACT FROM AUTHOR]

Various seeds, including sea buckthorn (Hippophae rhamnoides L.) seeds, are sources of different bioactive compounds. They can show anti-inflammatory, hypoglycemic, anti-hyperlipidemic, antibacterial, antioxidant, or other biological properties in in vitro and in vivo models. Our preliminary in vitro results have demonstrated that the extracts from raw (no thermal processing) and roasted (thermally processed) sea buckthorn seeds have antioxidant potential and anticoagulant activity. However, it was unclear which compounds were responsible for these properties. Therefore, in continuation of our previous study, the extracts were fractionated by C18 chromatography. Phytochemical analysis of three fractions (a, b, and c) from raw sea buckthorn seeds and four fractions (d, e, f, and g) from roasted sea buckthorn seeds were performed. Several in vitro assays were also conducted to determine the antioxidant and procoagulant/anticoagulant potential of the fractions and two of their major constituents—isorhamnetin 3-O-β-glucoside7-O-α-rhamnoside and serotonin. LC–MS analyses showed that serotonin is the dominant constituent of fractions c and f, which was tentatively identified on the basis of its HRMS and UV spectra. Moreover, fractions c and f, as well as b and e, contained different B-type proanthocyanidins. Fractions b and e consisted mainly of numerous glycosides of kaempferol, quercetin, and isorhamnetin. The results of oxidative stress assays (measurements of protein carbonylation, lipid peroxidation, and thiol groups oxidation) showed that out of all the tested fractions, fraction g (isolated from roasted seeds and containing mainly dihexoses, and serotonin) demonstrated the strongest antioxidant properties. [ABSTRACT FROM AUTHOR]

Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient's metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC. [ABSTRACT FROM AUTHOR]

Background: The peripartum period constitutes a delicate physiological moment in mares showing a transient state of oxidative stress. Diet supplementation with antioxidants during pregnancy in women appears to have a beneficial effect on mother and neonate health. The aim of this work was to evaluate the effects of diet supplementation with a commercial product containing a mix of antioxidants (Oxyliver®, Candioli) on the length of gestation, weight, and haemato-biochemical parameters in Italian Salernitano mares and their newborn foals. Eight late-term pregnant mares were randomly divided into two groups: Antiox group receiving 30 g/day of antioxidants, and Car group receiving the same amount of carrot powder, from 290 to 320 days of gestation. The following parameters were evaluated in mares: weight, colostrum composition, haemato-biochemical parameters, progesterone, and cortisol blood concentrations, along with blood oxidant/antioxidant status. Assessments were conducted at specific time points: immediately before the start of diet supplementation (T0), 15 days after (T1), at the end of diet supplementation (T2), within 8 h after parturition (T3), and 10 days post-partum (T4). Foal parameters such as weight, haemato-biochemical values, cortisol concentration, and blood oxidative stress variables were assessed within 8 h of birth (TF0) and at 10 days of age (TF1). Results: Pregnancy was shorter in the Antiox group (P < 0.05) compared with the Car group; the foals' weight increase of group Antiox (40%) was higher (P < 0.05) compared to those of the Car group (28.6%). The colostrum of the Antiox group exhibited higher levels of Brix, total solids, protein, nonfat solids, casein, urea, density, free fatty acids, and glucose, while lower levels of fat and lactose were observed compared to the Car group (P < 0.05). Mares' serum albumin at T1 and T3, creatinine, glucose, total proteins, total bilirubin, AST, and ALT at T3 were lower in Antiox than in the Car group. No significant differences were found in foals. Conclusions: While the limited sample size and the potential variability of evaluated parameters, the observed outcomes suggest that Oxyliver® supplementation in mares might safely decrease gestation length and enhance liver function, thus potentially improving colostrum quality and offspring development. [ABSTRACT FROM AUTHOR]

Background: Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. Methods: This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. Results: Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. Conclusion: Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM. [ABSTRACT FROM AUTHOR]

Background: Acute pulmonary embolism (APE) is a major type of venous thromboembolism (VTE) with a high risk of mortality and disability. There is a lack of biomarkers for APE to indicate deteriorating development and predict adverse outcomes. This study evaluated the significance of miR-150-5p in APE aiming to explore a novel potential biomarker for APE. Methods: The study enrolled APE (n = 137) and deep wein thrombosis (DVT, n = 67) patients and collected plasma samples from all study subjects. The expression of miR-150-5p was analyzed by PCR and its significance in screening APE and pulmonary arterial hypertension (PAH) was assessed by receiver operating curve (ROC) and logistic analyses. The study established oxidized low-density lipoprotein (ox-LDL)-induced human venous endothelial cells (HUVECs). Through cell transfection combined with cell counting kit-8 (CCK8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA), the effect of miR-150-5p on ox-LDL-induced HUVEC injury was evaluated. Results: Significant downregulation of miR-150-5p was observed in the plasma of APE patients compared with DVT patients (P < 0.0001). The plasma miR-150-5p levels in APE patients occurred PAH was much lower than in patients without PAH (P < 0.0001). Reducing miR-150-5p distinguished APE patients from DVT patients (AUC = 0.912) and was identified as a risk factor for the occurrence of PAH in APE patients (OR = 0.385, P = 0.010). In HUVECs, oxidized low-density lipoprotein (ox-LDL) caused inhibited cell proliferation, enhanced apoptosis, increased pro-inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and decreased superoxide dismutase (SOD). Overexpressing miR-150-5p could promote proliferation, inhibit apoptosis, and alleviate inflammation and oxidative stress of ox-LDL-treated HUVECs. Conclusions: Downregulated plasma miR-150-5p served as a diagnostic biomarker for APE and predicted the predisposition of PAH in APE patients. Overexpressing miR-150-5p could alleviate ox-LDL-induced endothelial cell injury in HUVECs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the mechanism underlying particulate matter (PM) exposure-induced oxidative stress and potential rescue strategies against pulmonary damage in this context. Methods: A combination of omics technology and bioinformatic analysis were used to uncover mechanisms underlying cellular responses to PM exposure in human bronchial epithelia (HBE) cells and imply the potential rescue. Results: Our results implicated that oxidative stress, metal ion homeostasis, and apoptosis were the major cellular responses to PM exposure in HBE cells. PM exposure disrupted oxidative phosphorylation (OXPHOS)-related gene expressions in HBE cells. Rescuing the expression of these genes with supplemental coenzyme Q10 (Co Q10) inhibited reactive oxygen species (ROS) generation; however, it only partially protected HBEs against PM exposure-induced apoptosis. Further, metallothionein (MT)-encoding genes associated with metal ion homeostasis were significantly induced in HBE cells, which was transcriptionally regulated by specificity protein 1 (SP1). SP1 knock-down (KD) aggravated PM-induced apoptosis in HBE cells, suggesting it plays a role in MT induction. Subsequent studies corroborated the protective role of MT by showing that exogenous MT supplement demonstrated effective protection against PM-induced oxidative stress and apoptosis in HBE cells. Importantly, exogenous MT supplement was shown to reduce ROS generation and apoptosis in airway epithelia in both HBE cells and a PM-inhaled murine model. Conclusion: This study demonstrates that the impact of MT on airway epithelia by suppressing oxidative stress and maintaining metal ion homeostasis is beneficial in attenuating damage to pulmonary cells undergoing PM exposure. [ABSTRACT FROM AUTHOR]

Pyroptosis induced by oxidative stress is a significant contributor to mental health disorders, including depression (+)-Catechin (CA), a polyphenolic compound prevalent in various food sources, has been substantiated by prior research to exhibit potent antioxidant properties and potential antidepressant effects. Nonetheless, the precise antidepressive mechanisms and effects of CA remain incompletely elucidated. In this study, we employed corticosterone (CORT) and PC12 cells to develop a cellular model of depression, aiming to investigate the protective effects of CA against CORT-induced cellular damage. Our objective was to elucidate the underlying mechanisms of protective action. We utilized transcriptomic analysis to identify differentially expressed genes and employed bioinformatics approaches to predict the potential mechanisms of CA's protective effects in PC12 cells. These transcriptomic predictions were subsequently validated through western blot analysis. The findings indicated that CA possesses the capacity to mitigate oxidative stress and suppress pyroptosis in PC12 cells via the activation of the PI3K/AKT signaling pathway. This activation subsequently modulates the Nrf2/HO1/NF-κB pathways, thereby providing protection to PC12 cells against damage induced by CORT. Furthermore, we investigated the interaction between CA and the Keap1 protein employing molecular docking and protein thermal shift assays. We propose that CA can activate Nrf2 through two mechanisms to decrease reactive oxygen species (ROS) levels and inhibit pyroptosis: one mechanism involves the activation of the PI3K/AKT signaling pathway, and the other involves direct binding to Keap1, leading to an increase in p-Nrf2. [ABSTRACT FROM AUTHOR]

The exploration of targeted therapy has proven to be a highly promising avenue in the realm of drug development research. The human body generates a substantial amount of free radicals during metabolic processes, and if not promptly eliminated, these free radicals can lead to oxidative stress, disrupting homeostasis and potentially contributing to chronic diseases and cancers. Before the development of contemporary medicine with synthetic pharmaceuticals and antioxidants, there was a long-standing practice of employing raw, natural ingredients to cure a variety of illnesses. This practice persisted even after the active antioxidant molecules were known. The ability of natural antioxidants to neutralise excess free radicals in the human body and so prevent and cure a wide range of illnesses. The term "natural antioxidant" refers to compounds derived from plants or other living organisms that have the ability to control the production of free radicals, scavenge them, stop free radical-mediated chain reactions, and prevent lipid peroxidation. These compounds have a strong potential to inhibit oxidative stress. Phytochemicals (antioxidants) derived from plants, such as polyphenols, carotenoids, vitamins, and others, are central to the discussion of natural antioxidants. Not only may these chemicals increase endogenous antioxidant defenses, affect communication cascades, and control gene expression, but they have also shown strong free radical scavenging properties. This study comprehensively summarizes the primary classes of natural antioxidants found in different plant and animal source that contribute to the prevention and treatment of diseases. Additionally, it outlines the research progress and outlines future development prospects. These discoveries not only establish a theoretical groundwork for pharmacological development but also present inventive ideas for addressing challenges in medical treatment. [ABSTRACT FROM AUTHOR]

Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors. Highlights: The first to report ghrelin' protective effect on H2O2-induced RPE cells. Treatment with ghrelin inhibits NaIO3-induced retinal cell apoptosis in vivo. Combined with in vitro and in vivo experiments, the results are comprehensive and reliable. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the second most common and lethal gynecologic malignancy. Among natural product-based therapy, the honeybee products, particularly propolis, serve a valuable source contributing directly to human nutrition and health. In the present study, we determined the chemical composition of different types of propolis originating from Egypt, Germany and France using liquid chromatography-tandem mass spectrometry. The compounds identified belong to different metabolite classes, including flavonoids, cinnamic acid, chalcones, terpenoids, phenolic lipids, stilbenes, phenolic compounds, carbohydrates, vitamins, coumarins, polyprenylated benzophenone, benzoic acids, fatty acid methyl ester, and coumaric acid, and their derivatives. The most active extract is from France then Egypt and Germany. Afterwards, we treated the human ovarian cancer cells, OVCAR4, with different concentrations (1–400 μg/mL) of variable propolis types supplemented or not with vitamin D (0.0015–0.15 μg/mL) in order to evaluate the efficacy and the cytotoxic activities of our local P as compared to other types collected from different geographic regions. Importantly, the combinatorial treatment of OVCAR4 cancer cells with propolis and vitamin D in the same concentration ranges resulted in enhanced cell viability inhibition. Furthermore, such co-supplementation with vitamin D inhibits predominately the proliferative activity of cell population with the French propolis type as manifested by Ki67 expression, while it reduces considerably its expression, particularly with the German type, followed by the Egyptian one. Nowadays, scientists are interested by natural products which have risen to the forefront of drug discovery. Chemically characterized propolis showing cell viability inhibition and antiproliferative potential seems a valuable extract for further consideration as anti-carcinogenic agent. [ABSTRACT FROM AUTHOR]

Hydroxyapatite nanoparticles (HANPs) have extensive applications in biomedicine and tissue engineering. However, little information is known about their toxicity. Here, we aim to investigate the possible neurotoxicity of HANPs and the possible protective role of chitosan nanoparticles (CNPs) and curcumin nanoparticles (CUNPs) against this toxicity. In our study, HANPs significantly reduced the levels of neurotransmitters, including acetylcholine (Ach), dopamine (DA), serotonin (SER), epinephrine (EPI), and norepinephrine (NOR). HANPs significantly suppressed cortical expression of the genes controlling mitochondrial biogenesis such as peroxisome proliferator activator receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (mTFA). Our findings revealed significant neuroinflammation associated with elevated apoptosis, lipid peroxidation, oxidative DNA damage and nitric oxide levels with significant decline in the antioxidant enzymes activities and glutathione (GSH) levels in HANPs-exposed rats. Meanwhile, co-supplementation of HANP-rats with CNPs and/or CUNPs significantly showed improvement in levels of neurotransmitters, mitochondrial biogenesis, oxidative stress, DNA damage, and neuroinflammation. The co-supplementation with both CNPs and CUNPs was more effective to ameliorate HANPs-induced neurotoxicity than each one alone. So, CNPs and CUNPs could be promising protective agents for prevention of HANPs-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence links vitamin D deficiency to oxidative stress (OS) and inflammation, posing ongoing risks to cardiovascular outcomes in hemodialysis (HD) patients. Despite this, current data are lacking regarding the optimal approach or schedule for administering vitamin D in this population. This study investigated the effectiveness of oral weekly versus oral monthly cholecalciferol supplementation on 25-hydroxy vitamin D (25(OH)D) levels, oxidative stress, inflammatory indicators, and secondary hyperparathyroidism in HD population. HD patients (N = 50) were randomly allocated to Group A (oral weekly 50,000 IU cholecalciferol) or Group B (oral monthly 200,000 IU cholecalciferol) for a 3 months duration. Serum levels of 25(OH)D, malondialdehyde (MDA), superoxide dismutase (SOD), high sensitivity C-reactive protein (HsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and intact parathyroid hormone (iPTH) were assessed at baseline and upon completion of the study. Results: A notable increase in serum 25(OH)D levels observed in both groups, with Group A showing a notably greater increase (p = 0.003). Group A demonstrated significant reductions in serum MDA and increases in SOD, along with declines in hsCRP and NLR levels, which were not observed in Group B. Moreover, Group A exhibited a greater drop in iPTH (ΔiPTH = − 30 pg/mL vs. − 3 pg/mL) compared to Group B. Clinicaltrial.gov: NCT05460338, registered 13/07/2022. Conclusions: Weekly oral 50,000 IU cholecalciferol supplementation emerges as a tolerable, safe and effective approach for restoring vitamin D levels in HD patients, while concurrently mitigating inflammation, OS, and secondary hyperparathyroidism. This finding suggests that the more frequent the administration of oral cholecalciferol, the higher the efficiency observed. [ABSTRACT FROM AUTHOR]

AbstractThe study aimed to assess the toxic effect of cadmium (Cd) on the exocrine and endocrine functions of pancreas, the changes in pancreatic tissue after Cd withdrawal, and the protective effects of vitamin C (VC) and Nigella sativa (NS) against Cd-induced damage. Rats were assigned to: control, Cd-treated (0.5 mg/kg/d intraperitoneal [IP] injection), VC and Cd-treated (receiving 100 mg/kg/d VC orally and Cd concomitantly), NS and Cd-treated (receiving 20 mg/kg/d NS and Cd, simultaneously), and Cd withdrawal (receiving Cd for 30 d then living free for recovery for other 30 d). Blood samples were collected and post-sacrifice pancreatic specimens were processed for light and electron microscope study. Quantitative analyses of pancreatic collagen area%, pancreatic islet parameters, β cell density, and insulin immunoexpression were done. Fasting blood glucose was significantly increased in Cd-treated and Cd-withdrawal groups, while co-treatment with VC and NS caused significant reductions (p < 0.05). Cd-induced extensive degenerative changes in pancreatic acini and islets at light and ultrastructure levels. Obvious fibrosis and congestion of blood vessels were noticed. Significant reductions in pancreatic islet number, volume, and surface area and diminished beta cell count and insulin immunoexpression were observed. After withdrawal of Cd, the whole pancreatic tissue still showed a serious impact. Concomitant treatment with VC or NS obviously reduced these degenerative changes and significantly improved pancreatic islet parameters and insulin immunoexpression. VC showed a better amendment than NS, but this difference was statistically insignificant. Therefore, VC and NS could be used as prophylactic agents that lessen Cd consequences on the pancreas. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cells are used in flap ischemia-reperfusion injury due to their antioxidant and inflammatory inhibition, and angiogenesis induction. OBJECTIVE: To review the mechanism and latest treatment progress of mesenchymal stem cells in the treatment of flap ischemia-reperfusion injury, and to provide a basis for further theoretical research and clinical rational application. METHODS: We searched the relevant articles indexed in CNKI, WanFang and PubMed databases. Chinese and English search terms were “mesenchymal stem cells; flap ischemia reperfusion injury; conditioned medium; exosomes; oxidative stress; inflammatory reactions; angiogenesis”. Relevant literature since 2010 was searched, and 74 articles were finally included after excluding the literature that had little to do with the topic of the article, poor quality and outdated content. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells play significant roles in antioxidation, inhibition of inflammation and induction of angiogenesis and have great potential in the treatment of flap ischemia-reperfusion injury. (2) However, the defects of mesenchymal stem cells themselves and the decline of therapeutic effect in recent years have put the development and application of mesenchymal stem cells into a bottleneck period, and the research on the plasticity of mesenchymal stem cells conditioned medium and its exosomes and mesenchymal stem cells came into being, and the therapeutic effect was significantly better than the use of mesenchymal stem cells alone. (3) Therefore, a more comprehensive understanding of the mechanism of action and the latest treatment progress of mesenchymal stem cells in the treatment of flap ischemia-reperfusion injury is of great significance for the research of mesenchymal stem cells and the treatment of flap ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Current studies have confirmed that Ganoderma lucidum polysaccharides can promote nerve regeneration in neurodegeneration-related diseases. The occurrence of neurodegenerative diseases is closely related to mitochondrial dysfunction, but the role of Ganoderma lucidum polysaccharides on the regulation of apoptosis and mitochondrial function in neurodegenerative diseases is not yet clarified. OBJECTIVE: To explore the regulatory effects and mechanisms of Ganoderma lucidum polysaccharides on apoptosis and mitochondrial dysfunction in H2O2- induced SH-SY5Y cells. METHODS: SH-SY5Y cells were divided into three groups: control group, H2O2 group, and Ganoderma lucidum polysaccharides group. Cells in the control group were normally cultured. Cells in the H2O2 group were treated with 300 μmol/L H2O2 for 24 hours. In the Ganoderma lucidum polysaccharides group, the intervention with 300 μg/L Ganoderma lucidum polysaccharides was conducted first for 1-2 hours, followed by the addition of 300 μmol/L H2O2 for 24 hours. The mitochondrial membrane potential was detected by JC-1 kit. Apoptosis was detected by TUNEL staining kit. The activities of malondialdehyde and superoxide dismutase were detected by malondialdehyde test kit and superoxide dismutase test kit, respectively. The apoptosis and expression of mitochondrial dynamics-related proteins were detected by immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION: (1) Compared with the control group, the mitochondrial membrane potential and superoxide dismutase activity were significantly reduced, as well as apoptotic rate and malondialdehyde levels were significantly increased in the H2O2 group (P < 0.05). After treatment with Ganoderma lucidum polysaccharides, the membrane potential and superoxide dismutase activities were significantly increased, and apoptotic rate and malondialdehyde levels were significantly reduced compared with the H2O2 group (P < 0.05). (2) The expression levels of pro-apoptotic proteins Bax and Caspase-3 were significantly increased, but the expression of anti-apoptotic protein Bcl-2 was significantly decreased in the H2O2 group compared with the control group (P < 0.05). Compared with the H2O2 group, the levels of Bax and Caspase-3 were significantly decreased, but the expression of anti-apoptotic protein Bcl-2 was significantly increased in the Ganoderma lucidum polysaccharides group (P < 0.05). (3) Compared with the control group, the expression of mitochondrial splitting proteins Fis1 and p-Drp1 was significantly increased, but the expression of mitochondrial fusion proteins OPA1, Mfn1, and Mfn2 was decreased in the H2O2 group (P < 0.05). Compared with the H2O2 group, Fis1 and p-Drp1 expression was significantly reduced, but the expression levels of OPA1, Mfn1, and Mfn2 were significantly increased in the Ganoderma lucidum polysaccharides group (P < 0.05). (4) The above results confirm that Ganoderma lucidum polysaccharides can attenuate H2O2-induced oxidative stress damage and apoptosis in SH-SY5Y cells by ameliorating mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background: Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows. Results: In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries. Conclusions: These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. Results: This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and •OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. Conclusion: Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]