Oxidative Stress Research Articles

Environmental behavior and toxic effects of micro(nano)plastics and engineered nanoparticles on marine organisms under ocean acidification: a review.

Ocean acidification (OA) driven by human activities and climate change presents new challenges to marine ecosystems. At the same time, the risks posed by micro(nano)plastics (MNPs) and engineered nanoparticles (ENPs) to marine ecosystems are receiving increasing attention. Although previous studies have uncovered the environmental behavior and the toxic effects of MNPs and ENPs under OA, there is a lack of comprehensive literature reviews in this field. Therefore, this paper reviews how OA affects the environmental behavior of MNPs and ENPs, and summarizes the effects and the potential mechanisms of their co-exposure on marine organisms. The review indicates that OA changes the marine chemical environment, thereby altering the behavior of MNPs and ENPs. These changes affect their bioavailability and lead to co-exposure effects. This impacts marine organisms' energy metabolism, growth and development, antioxidant systems, reproduction and immunity. The potential mechanisms involved the regulation of signaling pathways, abnormalities in energy metabolism, energy allocation, oxidative stress, decreased enzyme activity, and disruptions in immune and reproductive functions. Finally, based on the limitations of existing research, actual environment and hot issues, we have outlined future research needs and identified key priorities and directions for further investigation. This review deepens our understanding of the potential effects of MNPs and ENPs on marine organisms under OA, while also aiming to promote further research and development in related fields.

DanShen Decoction targets miR-93-5p to provide protection against MI/RI by regulating the TXNIP/NLRP3/Caspase-1 signaling pathway

BackgroundBone marrow mesenchymal stem cells (BMSCs) derived exosomes have demonstrated potential therapeutic efficacy on myocardial ischemia/reperfusion injury (MI/RI). This study has explored the underlying mechanisms of Danshen decoction (DSD) pretreated BMSCs-exosomes to treat MI/RI in vivo and in vitro. MethodsExtracellular vesicles extracted from BMSCs were identified, miRNA sequencing was performed to screen the effects of DSD, and verified to target TXNIP in vivo. After MI/RI modeling, rats were treated with BMSCs-exosomes pretreated with DSD or miRNA inhibitor. BMSCs-exosomes, DSD-pretreated BMSCs-exosomes, and miRNA inhibitor/anti-miRNA-pretreated BMSCs-exosomes were used to treat H9c2 cells or MI/RI rats. CCK-8, Tunnel staining, and flow cytometry were performed to measure cell viability. LDH, CK, CK-MB were detected to evaluate cell injury. MDA, SOD, and ROS were used to confirm oxidative stress. Furthermore, IL-1β, IL-18, cleaved-caspase-1, pro-caspase-1, NLRP3, TXNIP, and GSDMD were quantified for the TXNIP/NLRP3/Caspase-1 signaling activation. In addition, echocardiography was used to observe the heart function, and H&E stain was performed to detect pathological injury. ResultsFollowing DSD pretreatment, there was a marked elevation in the expression levels of miR-93-5p, miR-16-5p, and miR-15b-5p, with miR-93-5p exhibiting the highest baseMean value. The administration of a miR-93-5p inhibitor yielded effects counteractive to those observed with DSD treatment, leading to reduced cell proliferation, heightened oxidative stress (as indicated by increased levels of SOD and ROS, alongside a decrease in MDA), and enhanced cell apoptosis. Furthermore, DSD effectively mitigated the miR-93-5p-induced upregulation of key inflammatory and apoptotic markers, including IL-1β, IL-18, caspase-1, NLRP3, TXNIP, and GSDMD. Notably, exosomes derived from DSD-pretreated BMSCs demonstrated a capacity to alleviate cardiac damage. ConclusionDSD may target miR-93-5p within BMSC-derived exosomes to confer protection against cardiac damage by inhibiting the activation of the TXNIP/NLRP3/Caspase-1 signaling pathway, thereby mitigating cardiomyocyte pyroptosis. This study provides a theoretical foundation for the application of DSD in the treatment of MI/RI.

SP1-mediated transcriptional repression of SFRP5 is correlated with cardiac fibroblast activation and atrial myocyte apoptosis in the development of atrial fibrillation

Secreted frizzled related protein 5 (SFRP5) is a recognized cardioprotective protein with diminished expression in atrial fibrillation (AF). This study investigates SFRP5's function in AF-related cardiac fibrosis and cardiomyocyte apoptosis, exploring the underlying dysregulation causes. Utilizing C57BL/6 mice, mouse cardiac fibroblasts (CFs), and HC-1 mouse atrial myocyte cell line, AF models were induced by angiotensin Ⅱ (Ang Ⅱ). SFRP5 levels were consistently decreased in plasma samples from clinical patients, modeled mice, and CF culture supernatants. Treatment with recombinant SFRP5 restored its levels, mitigating Ang Ⅱ-induced AF in mice and ameliorating atrial tissue fibrosis and oxidative stress. In vitro, SFRP5 recombinant protein suppressed CF activation and fibrosis-related markers. The study identified Sp1 transcription factor (SP1) binding to the SFRP5 promoter, causing transcriptional repression. SP1 knockdown reinstated SFRP5 levels in mice and CFs, thus suppressing fibrosis. Additionally, SP1 knockdown attenuated Ang Ⅱ-induced apoptosis in HC-1 cells, but this effect was counteracted by concurrent SFRP5 knockdown. In conclusion, this investigation underscores that SP1 mediates SFRP5 loss during AF by transcriptional repression, contributing to fibrosis and myocyte apoptosis. These findings illuminate potential therapeutic interventions targeting the SFRP5-SP1 axis in AF-related cardiac complications.

Antibacterial carboxymethyl chitosan hydrogel loaded with antioxidant cascade enzymatic system for immunoregulating the diabetic wound microenvironment

Diabetic wound healing faces several complex challenges, such as hypoxia, oxidative stress, and bacterial infections, which severely inhibit the wound-healing process. Herein, a quaternary ammonium salt-crosslinked carboxymethyl chitosan hydrogel (TPC) with excellent antioxidant and antibacterial properties was developed to immunoregulate the diabetic wound microenvironment. The TPC hydrogel was prepared by first mixing carboxymethyl chitosan (CMCS) and protocatechualdehyde (PA), followed by the addition of a quaternary ammonium cross-linker (TSPBA) and a superoxide dismutase (SOD)–catalase (CAT) cascade system. The immobilized SOD and CAT retained their activity, continuously converting endogenous ·O2− and H2O2 to O2 and H2O. PA also provided the TPC hydrogel excellent oxygen and nitrogen radical scavenging capacity. The quaternary ammonium groups in TSPBA significantly enhanced the inherent antibacterial ability of CMCS-based hydrogels. In diabetic wound-healing experiments, this porous and adhesive TPC hydrogel effectively closed wounds and regenerated skin tissue, resulting in shorter wound edges, thicker granulation, and higher collagen deposition levels compared with other groups. The TPC hydrogel also promoted macrophage polarization toward the M2 phenotype, accelerating wound healing by upregulating IL-10 expression, downregulating IL-6 expression, and enhancing angiogenesis. These results demonstrate the great potential of TPC hydrogel as a promising therapeutic dressing for treating diabetic wounds.

Ecotoxicological Effects of Paracetamol on the Biochemical and Molecular Responses of Spinach (Spinacia oleracea L.)

The widespread use of pharmaceuticals, including paracetamol, has raised concerns about their impact on the environment and non-target species. The aim of this study was to investigate the biochemical and molecular responses of Spinacia oleracea (spinach) to high paracetamol concentrations in order to understand the plant's stress responses and underlying mechanisms. Under controlled conditions, spinach plants were exposed to different paracetamol concentrations (0, 50, 100, and 200mg/L). The study evaluated the impact of paracetamol exposure on biochemical parameters such as oxidative stress markers (H2O2, MDA), activities of antioxidant enzymes (APX, CAT, GPOD, SOD), levels of non-enzymatic components (phenolics and flavonoids), and phytohormones (ABA, SA, and IAA). Furthermore, the study assessed molecular impacts by analyzing stress-related genetic variation and alterations in the gene expression of the antioxidant enzymes. Results showed that paracetamol exposure significantly increased oxidative stress in spinach, which was evident through the elevated H2O2 and MDA levels. However, the antioxidant defense mechanisms were activated to counteract this effect, as evidenced by increased activity of antioxidant enzymes and higher phenolics and flavonoid levels. Moreover, induction in the phytohormone levels indicated a stress response in paracetamol-treated plants compared to control plants. RAPD analysis revealed polymorphism indicating the DNA damage, and the Real-time qRT-PCR method showed significant upregulation of stress-responsive genes, highlighting the severe impact of paracetamol at the molecular level. The study concludes that high paracetamol concentrations pose a significant threat to spinach growth by affecting both biochemical and molecular processes. These findings underscore the need for strict environmental management practices to mitigate the possible impact of continuous release, accumulation, and long-term exposure of pharmaceutical contaminants to the environment and implement policies to reduce pharmaceutical pollutants to preserve ecological health and biodiversity.

Mechanisms underlying Th2-dominant pneumonia caused by plastic pollution derivatives (PPD): A molecular toxicology investigation that encompasses gut microbiomics and lung metabolomics

An investigation was conducted by researchers on how dibutyl phthalate (DBP) and polystyrene microplastics (PS-MP) influence the development of pneumonia using a mouse model. For a duration of five weeks, the mice were subjected to exposure of DBP (30mg/kg/day) and PS-MP (0.1mg/day). The findings indicated notable pathological alterations in airway tissues, increased oxidative stress levels, and intensified inflammation, thereby establishing a connection between plastic pollution and pneumonia. Further examination indicated the involvement of ferroptosis and oxidative stress in the progression of the disease. Administration of deferoxamine (DFO) (100mg/kg) resulted in symptom relief and reduced pathological alterations, as validated by metabolomic investigations. Increased levels of reactive oxygen species (ROS) triggered a Th2-mediated eosinophilic inflammatory response, marked by elevated IL-4 and reduced IFN-γ via the NFκB pathway. Moreover, analyses of the gut microbiome and metabolomics demonstrated that PPD modifies microbial populations and pulmonary metabolism, linking its effects on pneumonia through the gut-lung axis. This research highlights the health hazards associated with plastic pollution and proposes a framework for tackling these issues.

The Association between High-density Lipoproteins and Periodontitis.

Periodontitis is one of the most typical chronic dental diseases. This inflammatory disease can change various functions of immune cells and impair lipid metabolism through proinflammatory cytokines. High-Density Lipoprotein (HDL) is considered protective of the cardiovascular system. It has anti-thrombotic and anti-inflammatory effects. In this article, we have reviewed the association between periodontitis and HDL. Various studies have demonstrated a reverse relationship between inflammatory cytokines and HDL. HDL contains antioxidative enzymes and proteins, whereas periopathogens impair HDL's antioxidant function. The presence of periodontal bacteria is associated with a low HDL level in patients with periodontitis. Genetic variants in the interleukin- 6 (IL)-6 gene and cytochrome (CYP)1A1 rs1048943 gene polymorphism are associated with HDL levels and periodontal status. Studies showed that HDL levels improve after treatment for periodontitis. On the one hand, periodontal pathogenic bacteria and their metabolites and pro-inflammatory cytokines from periodontal infection can result in various disorders of lipid metabolism and lipid peroxidation. On the other hand, hyperlipidemia and lipid peroxidation stimulate proinflammatory cytokines, resulting in oxidative stress and delayed wound healing, making individuals susceptible to periodontitis.

Transient cerebral ischaemia alters mesenteric arteries in hypertensive rats: Limited reversal despite suberoylanilide hydroxamic acid cerebroprotection.

Stroke induces brain injury, especially severe in hypertensive patients, and elevates mortality rates through non-neurological complications. However, the potential effects of a transient ischaemic episode on the peripheral vasculature of hypertensive individuals remain unclear. We investigated whether transient cerebral ischaemia (90 min)/reperfusion (1 or 8 days) induces alterations in mesenteric resistance artery (MRA) properties in adult male spontaneously hypertensive rats (SHR). In addition, we assessed whether the reported cerebroprotective effects of suberoylanilide hydroxamic acid (SAHA; 50 mg/kg; administered intraperitoneally at 1, 4, or 6 h after reperfusion onset) extend over several days and include beneficial effects on MRAs. Functional and structural properties of MRAs were examined at 1- and 8-days post-stroke. Nuclei distribution, collagen content, and oxidative stress were assessed. Ischaemic brain damage was evaluated longitudinally using magnetic resonance imaging. Following stroke, MRAs from SHR exhibited non-reversible impaired contractile responses to the thromboxane A2 receptor agonist U46619. Stroke increased the MRA cross-sectional area, wall thickness, and wall/lm ratio due to augmented collagen deposition. These changes were partially sustained 8 days later. SAHA did not improve U46619-induced contractions but mitigated stroke-induced oxidative stress and collagen deposition, preventing MRA remodelling at 24 h of reperfusion. Furthermore, SAHA induced sustained cerebroprotective effects over 8 days, including reduced brain infarct and oedema, and improved neurological scores. However, SAHA had minimal impact on chronic MRA contractile impairments and remodelling. These findings suggest that stroke causes MRA changes in hypertensive subjects. While SAHA treatment offers sustained protection against brain damage, it cannot fully restore MRA alterations.

Effect of Protocatechuic Acid on Tamoxifen Efficacy and Oxidative Stress in Breast Cancer Cells: Implications for Combination Therapy.

Effect of Protocatechuic Acid on Tamoxifen Efficacy and Oxidative Stress in Breast Cancer Cells: Implications for Combination Therapy.

Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.

One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.

Cuprorivaite microspheres inhibit cuproptosis and oxidative stress in osteoarthritis via Wnt/β-catenin pathway

This study aims to evaluate the therapeutic potential of cuprorivaite microspheres for osteoarthritis (OA), in particular, potential molecular mechanisms were investigated. The microspheres were developed from Ca(NO3)2•4H2O, Cu(NO3)2•3H2O, and silica gel, and further therapeutic effects were tested in vitro on mouse primary chondrocytes treated with interleukin-1β (IL-1β) to mimic OA, and in vivo on OA mice induced via anterior cruciate ligament transection (ACLT) surgery. The microspheres were shown to mitigate IL-1β-induced apoptotic, inflammatory, and oxidative stress markers while enhancing cell viability and extracellular matrix (ECM) components in chondrocytes. Moreover, the microspheres ameliorated histopathological damage, reduced inflammatory and oxidative stress markers, and enhanced ECM biomarker levels in OA mice, implicating their role in suppressing cuproptosis and oxidative stress. The aforementioned effects of the cuprorivaite microspheres were demonstrated by using SKL2001, an agonist of the Wnt/β-catenin pathway. The results suggest cuprorivaite microspheres as a promising intervention for OA and cartilage regeneration, highlighting their therapeutic effects on cellular and molecular levels.

Apigenin attenuates cisplatin-induced hair cell damage in the zebrafish lateral line

Cisplatin, a widely used chemotherapy drug, is notorious for causing ototoxicity, which leads to irreversible sensorineural hearing loss by damaging cochlear sensory hair cells (HCs), spiral ganglion neurons (SGNs), and the stria vascularis (SV). Mechanisms include DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammation, ultimately triggering cell death pathways like apoptosis, necroptosis, pyroptosis, or ferroptosis. Apigenin, a natural flavonoid found in various foods and beverages, possesses antioxidant, anti-inflammatory, and anti-tumor properties. Despite these benefits, its potential to mitigate cisplatin-induced ototoxicity remains unexplored. To investigate, we administered varying concentrations of apigenin (1 μM, 20 μM, 100 μM, and 250 μM) alongside cisplatin (200 μM) to zebrafish larvae at 5 days post fertilization. Cisplatin significantly reduced lateral line HCs, impacting auditory function as shown in startle response tests. However, co-administration with apigenin preserved lateral line HCs and mitigated cisplatin-induced hearing loss. In larvae exposed to cisplatin, TUNEL assay confirmed significant HCs apoptosis, which apigenin effectively countered by suppressing reactive oxygen species accumulation in lateral line HCs. RNA-seq analysis highlighted apigenin's role in modulating apoptosis-related pathways, supporting its protective effects against cisplatin-induced ototoxicity. These findings underscore apigenin's potential as a crucial protective agent against cisplatin-induced ototoxicity, meriting further investigation for clinical applications.

Utilization of Ziziphus spina-christi leaf extract-loaded chitosan nanoparticles in wastewater treatment and their impact on animal health

Ziziphus leaf extract (ZEX), chitosan nanoparticles (CS NPs) and Ziziphus leaf extract loaded chitosan nanoparticles (ZEX-CS NPs) were prepared in this study and after chemical analysis and characterization, they were used in wastewater purification. The study also aimed to establish, using an animal model, the feasibility of employing treated water in drinking applications. ZEX-CS NPs were prepared by ionic gelation method. About 25 male Sprague Dawley rats (10 weeks and 170-200 g) were divided into five groups (5 rats/group): group I received tape water; group II received untreated wastewater, group III received ZEX treated wastewater, group IV received CS NPs treated wastewater and group V received ZEX-CS NPs treated wastewater. ZEX-CS NPs have a size of 73 nm, hydrodynamic size of 85.81 nm and zeta potential of −33.68 mV. In addition, ZEX-CS NPs have stronger antioxidant and anti-inflammatory activity with moderate anti-coagulant activity and weaker cytotoxicity than ZEX and CS NPs. Group II showed a significant elevation in the kidney function parameters, oxidative stress and cytokine levels when compared to the other groups, in addition; no significant differences were found in all measured parameters between the rats of group I and V. ZEX-CS NPs were effective in wastewater purification.

Lactobacillus rhamnosus ZJUIDS07 ameliorates type 2 diabetes in mice through the microbiome-gut-pancreas axis

Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia, with its prevalence escalating. It exerts a profound impact on human health care and socio-economic development. Probiotics, known as natural, safe, and minimal side effects, have emerged as promising intervention agents to manage chronic diabetes. Our study aimed to explore the therapeutic potential of Lactobacillus rhamnosus ZJUIDS07 for mitigating T2D in mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Administration of L. rhamnosus ZJUIDS07 led to a reduction in diabetic symptoms, including reversal of weight loss, improvement in hyperglycemia and insulin resistance, mitigation of disruptions in glucose and lipid metabolism, alleviation of pancreatic pathological damage, and reduction in oxidative stress and inflammation. Moreover, treatment with L. rhamnosus ZJUIDS07 could restore intestinal microbiota balance in T2D mice by altering the structure and composition of intestinal microbiota, and increased short-chain fatty acids (SCFAs) levels. Specifically, L. rhamnosus ZJUIDS07 significantly decreased the abundance of harmful bacteria like Staphylococcus, Corynebacterium, and Odoribacte, while increasing the abundance of beneficial bacteria (especially SCFAs-producing bacteria) such as Muribaculaceae_norank, Dubosiella, Clostridium sensu stricto 1, Lactobacillus, and Faecalibaculum. Our findings highlight that L. rhamnosus ZJUIDS07 represents a promising probiotic strategy for future treatment of T2D, and that the modulation of gut microbiota and their metabolites through the microbiome-gut-pancreas axis play a pivotal role for the antidiabetic effects of L. rhamnosus ZJUIDS07.

The inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation in diabetic nephropathy by integrative approach of network pharmacology and experimental verification

BackgroundAlthough clinical strategies for diabetic nephropathy (DN) therapy include stringent blood pressure control through blockade of the renin-angiotensin system and management of hyperglycemia, the condition is still observed to progress relentlessly. PurposeTo elucidate the protective effects of rutin on podocytes in db/db mice with integrative approach of network pharmacology and experimental verification. MethodsThe study employs network pharmacology to identify common targets between rutin and DN, constructs a potential protein-protein interaction (PPI) network, and conducts Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking is utilized to evaluate the interaction between rutin and protein targets. Additionally, experimental validation is performed using db/db mice and human podocyte cell models. ResultsRutin has been found to have a significant renoprotective effect, reducing blood glucose, proteinuria, and improving renal function in db/db mice. Rutin's inhibition of Src kinase reduces the phosphorylation levels of EGFR and ERK, which may mitigate podocyte injury. Additionally, rutin exhibits antioxidant properties, capable of lowering the levels of reactive oxygen species (ROS) in kidney tissue and increasing the activity of antioxidant enzymes like superoxide dismutase (SOD). These effects help protect podocytes from oxidative stress, further supporting the potential application of rutin in the treatment of DN. ConclusionsThe inhibition of rutin on Src kinase blocks high glucose-induced EGFR/ERK transactivation and protects podocyte injury in DN, indicating it might serve as a promising therapeutic agent for podocyte-targeted therapies.

Polystyrene microplastics cause reproductive toxicity in male mice

Microplastics are a common environmental pollutant that disrupts the reproductive system of living organisms. We investigated the reproductive toxicity of 2μm polystyrene microplastics (PS-MPs) in mice and treated them with PS-MPs for 6 weeks. We demonstrated that PS-MPs decreased the gonadosomatic index and the serum concentration of pituitary-testicular axis hormones (Follicle-stimulating hormone, Luteinizing hormone, and testosterone). The PS-MPs treatment also reduced viable epididymal sperm number and sperm motility. Our results also demonstrated a marked decrease in tubular differentiation index, spermatogenesis index, repopulation index, and steroidogenic foci. The PS-MPs treated mice demonstrated marketed tissue damage in the testis. We also found that reproductive abnormality in PS-MPs treated mice accompanied by reduced antioxidant capacity elevated oxidative stress, and, elevated apoptotic signaling. It was observed that Endoplasmic reticulum (ER) stress markers, including GRP78 and Chop, were upregulated. Based on these findings, oxidative stress and endoplasmic reticulum stress may contribute to the decline in the steroidogenic function of Leydig cells with PS-MPs treated.

The Synergistic Effect of Curcumin and Piperine Nanoparticles on Methamphetamine-induced Neurotoxicity, Oxidative Stress, and Memory Impairments in Mice Brain

Background: Methamphetamine (METH) is a highly addictive neural stimulant that severely affects the CNS and can induce oxidative damage. Piperine and curcumin are active constituents that have numerous properties, including antioxidant, anti-inflammatory, and neuroprotective Objective: In this study, the synergistic effect of piperine and curcumin nanoparticles was investigated on the acute doses of METH-induced neurotoxicity in mice brains. Methods: METH (6 mg/kg, i.p) was administered to 14 groups of mice and piperine-curcumin nanoparticles at different doses (10, 20, 40 mg/kg and 20, 40 and 60 mg/kg, respectively) were administered. Open field test (OFT) and conditioned place preference (CPP) were used to investigate locomotor activity, anxiety-like behavior, and addictive behavior in mice. Oxidative stress biomarkers (reactive oxygen species (ROS), protein carbonyl content, lipid peroxidation, glutathione content, and mitochondrial function were evaluated in isolated brain mitochondria. Results: We found that piperine and curcumin nanoparticles significantly decreased hyperlocomotion and anxiety-like behavior in METH-treated mice. Also, METH enhanced CPP whilst piperine and curcumin nanoparticles suppressed the effect of METH-induced CPP. METH administration significantly increased ROS, protein carbonyl content, and lipid peroxidation and decreased glutathione content and mitochondrial function in the isolated brain mitochondria. Piperine and curcumin nanoparticles (at all doses) showed synergistic effects on reducing oxidative damages in a dosedependent manner compared to the METH group. Conclusion: In conclusion, combined piperine and curcumin nanoparticles showed greater neuroprotective effects against METH-induced neurotoxicity due to their greater permeability and better antioxidant properties than piperine and curcumin alone

The effect of Coix lachrymal L. seed extract on the expression of inflammation and fibrogenesis genes in human retinal pigment epithelial cells.

Proliferative vitreoretinopathy (PVR) is a vision-threatening condition associated with retinal-detachment (RD), primarily caused by fibrocellular scar membrane formation. This study investigates the therapeutic potential of adlay seed extract fractions in mitigating PVR-associated pathways, focusing on oxidative stress, proliferation, inflammation, and fibrogenesis in retinal pigment epithelial (RPE) cells. Adlay seed extract fractions (methanolic: MeOH and residual: Res) were obtained through solvent extraction and characterized for carbohydrate, protein, flavonoid content, and antioxidant activity. RPE cells were cultured, and their viability in response to adlay fractions was assessed using the MTT assay. Gene expression analysis of IL-1β, IL-6, LIF, TGF-β, Snail and α-SMA genes was conducted via real-time PCR after treatment with adlay fractions. The Res fraction exhibited higher levels of protein, carbohydrate, flavonoids, and phenols compared to the MeOH fraction, along with significantly enhanced antioxidant activity. Both fractions showed inhibitory effects on RPE cell viability, with the Res fraction demonstrating a more pronounced impact. Gene expression analysis revealed a significant decrease in IL-6 and TGF-β expression with the MeOH fraction treatment, while the Res fraction led to decreased expression of IL-6, LIF, TGF-β, Snail and α-SMA, indicating a more comprehensive modulation of PVR-associated pathways. This study highlights the potential therapeutic benefits of adlay seed extract fractions in mitigating PVR-associated pathways in RPE cells. The Res fraction, particularly rich in bioactive compounds and exhibiting potent antioxidant activity, shows promise in attenuating oxidative stress, proliferation, inflammation, and fibrogenesis, critical processes in PVR development. These findings underscore the potential of adlay seed extracts as a novel therapeutic strategy for PVR warranting further investigation and clinical validation.

Nutritional assessment and medical dietary therapy for management of obesity in patients with non-dialysis chronic kidney disease: a practical guide for endocrinologist, nutritionists and nephrologists. A consensus statement from the Italian society of endocrinology (SIE), working group of the club nutrition-hormones and metabolism; the Italian society of nutraceuticals (SINut), club ketodiets and nutraceuticals "KetoNut-SINut"; and the Italian society of nephrology

Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function. This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis.

Roles of mTOR-p70S6K signaling pathway and HO-1 inethylbenzene-induced hepatoxic effects in L02 cells.

Ethylbenzene (EB)-induced hepatotoxic effects has been indicated as oxidative damage and mitochondria-mediated apoptosis in vivo in our previous study, yet the mechanisms remain unclear. This study aimed to explore the role of the mTOR-p70S6K signaling pathway in EB-induced hepatoxic effects in vitro. Normal human hepatocytes (L02 cells) were exposed to different concentrations of ethylbenzene (0-10 mM) for 24 hours. In vitro, we found that EB treatment decreased the viability of L02 cells, via inducing oxidative stress, mitochondrial impairments, excessive apoptosis and autophagy. These were accompanied by the inactivation of the mTOR-p70S6K signaling cascade, as manifested by the decreased levels of related molecules Atg family proteins and Heme oxygenase-1 (HO-1). These findings were further confirmed by mTOR inhibitor treatment and immunofluorescence analysis. Jointly, our results indicate that EB induces hepatoxic effects by triggering mitochondrial impairments and excess apoptosis and autophagy in L02 cells via suppressing the mTOR-p70S6K signaling, and oxidative stress affects the passive up-regulation of HO-1.