Regulation Of Oxidative Stress Research Articles

Role of M6a Methylation in Myocardial Ischemia-Reperfusion Injury and Doxorubicin-Induced Cardiotoxicity.

Cardiovascular disease remains the leading cause of death worldwide, with acute myocardial infarction and anticancer drug-induced cardiotoxicity being the significant factors. The most effective treatment for acute myocardial infarction is rapid restoration of coronary blood flow by thrombolytic therapy or percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury (MI/RI) after reperfusion therapy is common in acute myocardial infarction, thus affecting the prognosis of patients with acute myocardial infarction. There is no effective treatment for MI/RI. Anthracyclines such as Doxorubicin (DOX) have limited clinical use due to their cardiotoxicity, and the mechanism of DOX-induced cardiac injury is complex and not yet fully understood. N6-methyladenosine (m6A) plays a crucial role in many biological processes. Emerging evidence suggests that m6A methylation plays a critical regulatory role in MI/RI and DOX-induced cardiotoxicity (DIC), suggesting that m6A may serve as a novel biomarker and therapeutic target for MI/RI and DIC. M6A methylation may mediate the pathophysiological processes of MI/RI and DIC by regulating cellular autophagy, apoptosis, oxidative stress, and inflammatory response. In this paper, we first focus on the relationship between m6A methylation and MI/RI, then further elucidate that m6A methylation may mediate the pathophysiological process of MI/RI through the regulation of cellular autophagy, apoptosis, oxidative stress, and inflammatory response. Finally, briefly outline the roles played by m6A in DIC, which will provide a new methodology and direction for the research and treatment of MI/RI and DIC.

The therapeutic potential of 1, 25-dihydroxy vitamin D3 on cisplatin-affected neurological functions is associated with the regulation of oxidative stress and inflammatory markers as well as levels of MMP2/9.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin.Induction of neurotoxicity was done with cisplatin administration (5mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments.Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels.Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

RAGE signalling contributes to oxidative stress and inflammation in knee osteoarthritis patients with metabolic syndrome.

Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO. This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome. We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well. We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.

Diagnostic value of selenoprotein changes in renal tissues for acute rejection of kidney transplantation as revealed by transcriptomics

BackgroundThere seems to be a close link between the changing levels of selenoproteins, which are important for maintaining redox homeostasis in the body, and acute rejection of kidney transplants. The aim of this study was to explore the diagnostic value of selenoprotein change characteristics in renal tissues for acute rejection of kidney transplantation. MethodsWe first explored the potential biological functions of 25 selenoproteins in the human body by enrichment analysis and used the HPA database to clarify the expression levels of selenoproteins in kidney tissues; We then constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”; Calibration curves and ROC curves were used to evaluate the diagnostic models, and clinical decision curves (DCA) were used to assess the diagnostic value of selenoprotein changes to the clinic; Single-gene GSEA enrichment analysis to further explore the potential regulatory mechanisms of selenoproteins; The Cibersort algorithm explores the level of immune cell infiltration and uses correlation analysis to clarify the correlation between selenoproteins and immune cells; We further assessed the diagnostic value of selenoproteins in kidney transplantation ABMR and TCMR, respectively. Finally, we validated the expression level of selenoproteins in kidney tissues by constructing a rat model of acute rejection of kidney transplantation using transcriptome sequencing. ResultsOur enrichment analysis revealed that selenoproteins are mainly closely associated with biological functions such as oxidative stress, inflammation, and immune regulation (P<0.05); The HPA database suggests that a total of 23 selenoproteins can be expressed in kidney tissue. We constructed a diagnostic model using these 23 selenoproteins, and both calibration curves and ROC curves proved that their change levels have good diagnostic value for acute rejection of kidney transplantation, and DCA curves proved the role of selenoproteins in clinical decision-making; Single-gene GSEA enrichment analysis revealed that selenoproteins are closely associated with immune regulation-related pathways (P<0.05); The Cibersort algorithm identified 10 immune cell infiltration levels that were significantly altered during acute rejection of kidney transplantation (P<0.05), while correlation analyses indicated that selenoproteins correlate with multiple immune cell infiltrations; In ABMR and TCMR, we again verified the diagnostic value of selenoprotein changes in acute rejection of kidney transplantation. Finally, we found significant differences in the expression levels of nine selenoproteins in a rat model of acute rejection of kidney transplantation (P<0.05) . ConclusionChanges in selenoproteins in renal tissues have good diagnostic value for acute rejection of kidneyl transplantation, and selenoproteins may be able to be a potential target for alleviating acute rejection of kidney transplantation.

MicroRNAs as Regulators of Radiation-Induced Oxidative Stress

MicroRNAs as Regulators of Radiation-Induced Oxidative Stress

A coupled model between circadian, cell-cycle, and redox rhythms reveals their regulation of oxidative stress

Most organisms possess three biological oscillators, circadian clock, cell cycle, and redox rhythm, which are autonomous but interact each other. However, whether their interactions and autonomy are beneficial for organisms remains unclear. Here, we modeled a coupled oscillator system where each oscillator affected the phase of the other oscillators. We found that multiple types of coupling prevent a high H2O2 level in cells at M phase. Consequently, we hypothesized a high H2O2 sensitivity at the M phase and found that moderate coupling reduced cell damage due to oxidative stress by generating appropriate phase relationships between three rhythms, whereas strong coupling resulted in an elevated cell damage by increasing the average H2O2 level and disrupted the cell cycle. Furthermore, the multicellularity model revealed that phase variations among cells confer flexibility in synchronization with environments at the expense of adaptability to the optimal environment. Thus, both autonomy and synchrony among the oscillators are important for coordinating their phase relationships to minimize oxidative stress, and couplings balance them depending on environments.

Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation.

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer membrane rupture, affecting mitochondrial function and cellular fate. Recent reports have described the intrinsic cellular iron metabolism and its intricate connection to ferroptosis, a significant kind of cell death characterized by iron dependence and oxidative stress regulation. Furthermore, updated molecular insights have elucidated the significance of mitochondria in ferroptosis and its implications in various cancers. In the context of cancer therapy, understanding the dual role of anastasis and ferroptosis in chemoresistance is crucial. Targeting the molecular pathways involved in anastasis may enhance the efficacy of ferroptosis inducers, providing a synergistic approach to overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, and redox states interact during anastasis and ferroptosis can offer new insights into designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit anastasis while simultaneously inducing ferroptosis, thereby reducing the likelihood of cancer cells evading death and developing resistance to chemotherapy. The objective of this study is to explore the intricate interplaybetween anastasis, ferroptosis, EMT and chemoresistance, and immunotherapeutics to better understand their collective impact on cancer therapy outcomes. We searched public research databases including google scholar, PubMed, relemed, and the national library of medicine related to this topic. In this review, we discussed the interplay between the tricarboxylic acid cycle and glycolysis implicated in modulating ferroptosis, adding complexity to its regulatory mechanisms. Additionally, the regulatory role of reactive oxygen species (ROS) and the electron transport chain (ETC) in ferroptosis has garnered significant attention. Lipid metabolism, particularly involving GPX4 and System Xc- plays a significant role in both the progression of ferroptosis and cancer. There is a need to investigate the intricate interplay between anastasis, ferroptosis, and chemoresistance to better understand cancer therapy clinical outcomes. Integrating anastasis, and ferroptosis into strategies targeting chemoresistance and exploring its potential synergy with immunotherapy represent promising avenues for advancing chemoresistant cancer treatment. Understanding the intricate interplay among mitochondria, anastasis, ROS, and ferroptosis is vital in oncology, potentially revolutionizing personalized cancer treatment and drug development.

Flying‐Saucer‐Shaped Nanoheterojunctions with Enhanced Colorectal Tumor Accumulation for Increased Oxidative Stress and Immunometabolic Regulation

AbstractThe treatment outcomes of nanomedicines against colorectal cancer are severely restricted by their insufficient accumulation in the tumor tissues, unsatisfactory antitumor effect, and weak immunometabolic modulation. To address these issues, flying‐saucer‐shaped nanoheterojunctions by coating copper oxide (CuxO) onto the surface of PEGylated zinc oxide (ZnO) nanoparticles are constructed. When exposed to ultrasound, the resultant CuxO@ZnO nanoheterojunctions exhibit increased locomotor activities, facilitating colorectal mucus infiltration, deep tumor penetration, and tumor cell internalization. The decoration of CuxO suppresses the rapid recombination of electrons and holes in CuxO@ZnO exposed to ultrasound, promoting the production of singlet oxygen and hydroxyl radical, which are generated by CuxO through a Fenton‐like chemodynamic reaction and CuxO@ZnO through sonodynamic reaction. After rectal administration, the sono‐chemodynamic CuxO@ZnO plus PD‐L1 antibodies effectively inhibit the growth of orthotopic and distant tumors. It elicits immunometabolic responses by inducing immunogenic cell death, activating the interferon genes signaling pathway stimulator, and inhibiting glucose transport and the glycolytic signaling pathways. This combined modality also increases the proportion of beneficial microbes (e.g., Bifidobacterium) and decreases the abundance of harmful microorganisms (e.g., Romboutsia) in the intestine. This treatment modality (CuxO@ZnO plus ultrasound and PD‐L1 antibodies) is a promising strategy for the synergistic treatment of colorectal cancer.

Impact of Pediococcus pentosaceus YF01 on the exercise capacity of mice through the regulation of oxidative stress and alteration of gut microbiota.

Using treadmill training, this study replicated human exercise conditions and triggered exercise-induced fatigue in mice to examine the potential of Pediococcus pentosaceus YF01 in delaying this fatigue by regulating oxidative stress and its impact on the exercise capacity and gut microbiota of mice. The exercise capacity of mice was tested by conducting exhaustion tests, determining histopathological changes in mouse tissues, detecting the levels of serum biochemical markers, and evaluating the mRNA expression levels of relevant genes. YF01 prolonged the exhaustion time of mice, increased the serum levels of oxidative stress-related markers T-AOC, CAT, and GSH, as well as GLU and LA levels in the mice. YF01 decreased the levels of hepatic-related markers AST and ALT, as well as exercise-related markers LDH, BUN, UA, and CRE in the mice. YF01 upregulated the mRNA expression of MyHc I, SIRT1, and PGC in muscle tissues, as well as SOD1, SOD2, and CAT in both liver and muscle tissues. YF01 also downregulated the mRNA expression of MyHc IIa, MyHc IIb, and MyHc IIx in muscle tissues. Furthermore, YF01 increased the abundance of beneficial bacteria such as Lactobacillus and Lachnospiraceae in the gut microbiota of mice. In conclusion, P. pentosaceus YF01 may affect the exercise capacity of mice by modulating oxidative stress levels, thereby offering novel ideas for developing of sports science and human health.

Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions.

The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%-30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.

MiR-146a Decreases Inflammation and ROS Production in Aged Dermal Fibroblasts.

Aging is associated with a decline in the functionality of various cell types, including dermal fibroblasts, which play a crucial role in maintaining skin homeostasis and wound healing. Chronic inflammation and increased reactive oxygen species (ROS) production are hallmark features of aging, contributing to impaired wound healing. MicroRNA-146a (miR-146a) has been implicated as a critical regulator of inflammation and oxidative stress in different cell types, yet its role in aged dermal fibroblasts and its potential relevance to wound healing remains poorly understood. We hypothesize that miR-146a is differentially expressed in aged dermal fibroblasts and that overexpression of miR-146a will decrease aging-induced inflammatory responses and ROS production. Primary dermal fibroblasts were isolated from the skin of 17-week-old (young) and 88-week-old (aged) mice. Overexpression of miR-146a was achieved through miR-146a mimic transfection. ROS were detected using a reliable fluorogenic marker, 2,7-dichlorofluorescin diacetate. Real-time PCR was used to quantify relative gene expression. Our investigation revealed a significant reduction in miR-146a expression in aged dermal fibroblasts compared to their younger counterparts. Moreover, aged dermal fibroblasts exhibited heightened levels of inflammatory responses and increased ROS production. Importantly, the overexpression of miR-146a through miR-146a mimic transfection led to a substantial reduction in inflammatory responses through modulation of the NF-kB pathway in aged dermal fibroblasts. Additionally, the overexpression of miR-146a led to a substantial decrease in ROS production, achieved through the downregulation of NOX4 expression in aged dermal fibroblasts. These findings underscore the pivotal role of miR-146a in mitigating both inflammatory responses and ROS production in aged dermal fibroblasts, highlighting its potential as a therapeutic target for addressing age-related skin wound healing.

Regulation of Oxidative Stress and Apoptosis in Streptozotocin-Induced Diabetic Rats by Egyptian Sidr Honey.

Diabetes mellitus is a global health issue characterized by hyperglycemia which leads over time to severe damage to numerous tissues. The present study aimed to estimate the effect of Egyptian Sidr honey against streptozotocin (STZ)-induced diabetes in rats. Diabetic rats were treated with Sidr honey daily for 4 consecutive weeks. The biochemical profile of blood samples was measured. Furthermore, the activity of antioxidant enzymes, nitric oxide (NO), and malonaldehyde (MDA) were examined in hepatic and pancreatic tissues. Moreover, the expression of Bax, Caspase-3, and Bcl2 proteins were measured. Results revealed that the capability of Sidr honey to decline the elevated blood glucose and fructosamine levels. Also, the honey decreased the levels of NO and MDA. Furthermore, it regulated the antioxidant enzymes activity. Moreover, it reduced the expression levels of Caspase-3 and Bax while increased the Bcl2 level. In conclusion, Sidr honey can regulate hyperglycemia, oxidative stress, apoptosis, and antioxidant enzymes in STZ-induced diabetic rats.

Auranofin and reactive oxygen species inhibit protein synthesis and regulate the level of the PLK1 protein in Ewing sarcoma cells.

Novel therapeutic approaches are needed for the treatment of Ewing sarcoma tumors. We previously identified that Ewing sarcoma cell lines are sensitive to drugs that inhibit protein translation. However, translational and therapeutic approaches to inhibit protein synthesis in tumors are limited. In this work, we identified that reactive oxygen species, which are generated by a wide range of chemotherapy and other drugs, inhibit protein synthesis and reduce the level of critical proteins that support tumorigenesis in Ewing sarcoma cells. In particular, we identified that both hydrogen peroxide and auranofin, an inhibitor of thioredoxin reductase and regulator of oxidative stress and reactive oxygen species, activate the repressor of protein translation 4E-BP1 and reduce the levels of the oncogenic proteins RRM2 and PLK1 in Ewing and other sarcoma cell lines. These results provide novel insight into the mechanism of how ROS-inducing drugs target cancer cells via inhibition of protein translation and identify a mechanistic link between ROS and the DNA replication (RRM2) and cell cycle regulatory (PLK1) pathways.

Attenuating intervertebral disc degeneration through spermidine-delivery nanoplatform based on polydopamine for persistent regulation of oxidative stress

As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.

Modulation of secondary metabolism and redox regulation by exogenously applied glutathione improves the shelf life of Capsicum annuum L. fruit

Role of redox homeostasis in fruit ripening of Capsicum annuum L. with oxidative metabolism was studied. The research aims the ability to reduce agents during postharvest storage on fruit for delayed ripening with the regulation of oxidative stress. Thus, we applied 10 mM reduced glutathione (GSH) to fruit as pretreatment followed by 1 mM hydrogen peroxide (H2O2) as ripening-inducing treatment and observed during 7 days of storage at 25 °C. A decrease in total soluble solid and firmness under H2O2, was increased while dehydration in tissue was decreased by GSH pretreatment. Glutathione regulated the turnover of organic acids to reducing sugars with higher activity of NADP malic enzyme that sustained the fruit coat photosynthesis through chlorophyll fluorescence, pigment composition, and photosystem II activity. Malondialdehyde accumulation was inversely correlated with GSH content and antioxidative enzyme activity that reduced loss of cell viability. Conclusively, regulation of oxidative stress with GSH may be effective in the extension of shelf life under postharvest storage.

Unveiling the protective role of anthocyanin in rice: insights into drought-induced oxidative stress and metabolic regulation.

This study investigates the impact of anthocyanin treatment on rice plants under drought stress, focusing on phenotypic, molecular, and biochemical responses. Anthocyanin were treated to one month old plants one week before the droughtexposure. Drought stress was imposed by using 10% polyethylene glycol (PEG 6000). Anthocyanin-treated plants exhibited significant enhancements in various traits, including growth parameters and reproductive characteristics, under normal conditions. When subjected to drought stress, these plants displayed resilience, maintaining or improving essential morphological and physiological features compared to non-treated counterparts. Notably, anthocyanin application mitigated drought-induced oxidative stress, as evidenced by reduced levels of reactive oxygen species (ROS) and lipid membrane peroxidation. The study also elucidates the regulatory role of anthocyanins in the expression of flavonoid biosynthetic genes, leading to increased levels of key secondary metabolites. Furthermore, anthocyanin treatment influenced the levels of stress-related signaling molecules, including melatonin, proline, abscisic acid (ABA), and salicylic acid (SA), contributing to enhanced stress tolerance. The enzymatic activity of antioxidants and the expression of drought-responsive genes were modulated by anthocyanins, emphasizing their role in antioxidant defense and stress response. Additionally, anthocyanin treatment positively influenced macronutrient concentrations, particularly calcium ion (Ca+), potassium ion (K+), and sodium ion (Na+), essential for cell wall and membrane stability. The findings collectively highlight the multifaceted protective effects of anthocyanins, positioning them as potential key players in conferring resilience to drought stress in rice plants. The study provides valuable insights into the molecular and physiological mechanisms underlying anthocyanin-mediated enhancement of drought stress tolerance, suggesting promising applications in agricultural practices for sustainable crop production.

Omega-3-Rich Tuna Oil Derived from By-Products of the Canned Tuna Industry Enhances Memory in an Ovariectomized Rat Model of Menopause.

To increase the value of the by-products of the canned tuna industry, the memory enhancement effect and the possible mechanisms of omega-3-rich tuna oil in bilateral ovariectomized (OVX) rats were assessed. Female rats were orally given tuna oil at doses of 140, 200, and 250 mg/kg of body weight (BW) for 28 days before OVX and for 21 days continually after OVX. Memory performance was assessed every week, whereas the parameters regarding mechanisms of action were assessed at the end of the study. All doses of tuna oil enhanced memory, docosahexaenoic acid (DHA) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities but decreased cortisol, acetylcholinesterase (AChE), malondialdehyde (MDA), and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Medium and high doses of tuna oil suppressed monoamine oxidase (MAO) but increased eNOS activity. A high dose of tuna oil suppressed gamma-aminotransferase (GABA-T) but increased glutamic acid decarboxylase (GAD) and sirtuin-1. A medium dose of tuna oil decreased homocysteine (Hcys) and C-reactive protein. No change in telomere or estradiol was observed in this study. Our results suggest the memory-enhancing effect of tuna oil in an OVX rat model of menopause. The main mechanisms may involve a reduction in oxidative stress, inflammation, and neurotransmitter regulation.

Protective effects of nodosin against lipopolysaccharide-induced acute kidney injury through regulation of oxidative stress, inflammation, and ferroptosis in rats.

This research aimed to explore the impact of nodosin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in rats. The study involved administering nodosin orally at doses of 2 and 4mg/kg body weight orally to rats for 7 days before induction of AKI. Toward the end of the study, urine, blood, and kidneys were gathered from the rats to undergo biochemical and molecular examination after sacrificing them. Serum Scr, BUN, urine NGAL, and KIM-1 levels were significantly decreased in nodosin-treated AKI rats. Besides, nodosin administration resulted in a significant reduction in kidney MDA and 4-HNE levels. In contrast, antioxidant enzymes such as SOD, CAT, GPx, and GST levels increased, as well as Nrf2, NQO1, and HO-1 levels increased, while Keap-1 mRNA levels decreased in AKI rats. In addition, AKI rats treated with nodosin reversed excessive ferroptosis in the kidneys of LPS-induced AKI rats, as evidenced by increased mRNA and protein levels of GPX4, SLC7A11, and FTH-1. The administration of nodosin significantly reduced levels of inflammatory markers including TLR4, MYD88, NF-κB p65, IkKβ, and IL-1β, while IL-10 levels increased in the AKI-induced rats. Besides, histopathological changes were reduced in AKI-induced rats treated with nodosin. Nodosin proves highly beneficial in safeguarding the kidney from AKI by regulating oxidative stress, inflammation, and ferroptosis. The treatment of AKI could greatly benefit from this option.

Stellate Ganglion Block Attenuates LPS-Induced Acute Lung Injury by Activating Sirt3 Regulation of Oxidative Stress and Inflammation.

Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1β, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1β and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.

Vitamin e succinate-glycol chitosan modified copper ferrite nanocomposites for lung cancer: Targeted oxidative stress regulation induces cuproptosis and ferroptosis

Although platinum-based drugs continue to be the mainstay of chemotherapy for non-small cell lung cancer (NSCLC), drug toxicity and resistance have caused considerable clinical problems. Copper species may overcome cisplatin-induced resistance, have a wider activity range, and be less toxic than platinum-based drugs. Despite the strong potential of copper-based nanomaterials to trigger cuproptosis and ferroptosis for the treatment of NSCLC, effectively targeting cancer cell death remains challenging. The copper ferrite nanocomposite (CF-GV-LBL) was designed to specifically induce tumor cell death by the responsiveness of vitamin E succinate-glycol chitosan (GV) polymers to cellular esterase levels, the protonation action of GV polymers and polylysine (PL) amino acids, and the active targeting of human serum albumin. Copper ferrite (CF) released iron and copper ions, increasing intracellular oxidative stress, depleting cellular glutathione, and initiating cuproptosis and ferroptosis. Because oxidative stress plays a crucial role in the processes of cuproptosis and ferroptosis, this work focuses on selectively regulating oxidative stress levels in intercellulars. In normal cells, GV degraded and produces the antioxidant vitamin E, which decreases cellular oxidative stress and subsequent damage. In cancer cells, GV generated reactive oxygen species, further promoting the occurrence of cuproptosis and ferroptosis. The CF-GV-LBL nanocomposite demonstrated greater anti-tumor efficacy and biocompatibility than carboplatin. Increased oxidative stress may activate the p53 signaling pathway, thus inhibiting tumor cell growth. Significantly, after 15 days of treatment, CF-GV-LBL efficiently suppressed the development of subcutaneous A549 tumors in the nude mice. Overall, this study focuses on providing insights for the treatment of NSCLC.