Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

CISD2 regulates oxidative stress and mitophagy to maintain the balance of the follicular microenvironment in PCOS.

OBJECTIVES: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS. METHODS: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage. RESULTS: We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress. CONCLUSIONS: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.

The antioxidant, anti-inflammatory, and anti-apoptotic effects of sesamin against cisplatin-induced renal and testicular toxicity in rats.

PURPOSE: The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries. METHODS: Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days. RESULTS: Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats' tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters' concentrations to normal ranges. CONCLUSIONS: In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Unveiling the ecotoxicological effects of azoxystrobin-based fungicides at realistic concentrations on the land snail, Theba pisana.

The ecotoxicological consequences of azoxystrobin on land snails have not yet been addressed. Therefore, the present study aims to provide novel data on the threat of a commercial grade azoxystrobin (AMISTAR) at two environmentally relevant concentrations (0.3 µg/ml) and tenfold (3 µg/ml) on the model species, Theba pisana by physiological, biochemical, and histopathological markers for 28 days. Our results showed a reduction in animal food consumption and growth due to exposure to both azoxystrobin concentrations. It also induced oxidative stress and led to a significant decrease in lipid peroxidation (LPO) levels after 7 days of exposure, while the opposite effect occurred after 28 days. Except for the 7-day exposure, all treated snails had significantly reduced glutathione (GSH) content and increased catalase (CAT) activity at all-time intervals. Glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities, and protein content (PC) were elevated in treated snails at all-time intervals. Moreover, alterations in acetylcholinesterase (AChE) activity between a decrease and an increase were noticed. Additionally, azoxystrobin exerted changes in T. pisana hepatopancreas architecture. Our study suggests that azoxystrobin may have negative ecological consequences for T. pisana and highlights its potential risks to the natural environment.

Establishing an oxidative stress mitochondria-related prognostic model in hepatocellular carcinoma based on multi-omics characteristics and machine learning computational framework.

Hepatocellular carcinoma (HCC) has high incidence and mortality rates worldwide. Damaged mitochondria are characterized by the overproduction of reactive oxygen species (ROS), which can promote cancer development. The prognostic value of the interplay between mitochondrial function and oxidative stress in HCC requires further investigation. Gene expression data of HCC samples were collected from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). We screened prognostic oxidative stress mitochondria-related (OSMT) genes at the bulk transcriptome level. Based on multiple machine learning algorithms, we constructed a consensus oxidative stress mitochondria-related signature (OSMTS), which contained 26 genes. In addition, we identified six of these genes as having a suitable prognostic value for OSMTS to reduce the difficulty of clinical application. Univariate and multivariate analyses verified the OSMTS as an independent prognostic factor for overall survival (OS) in HCC patients. The OSMTS-related nomogram demonstrated to be a powerful tool for the clinical diagnosis of HCC. We observed differences in biological function and immune cell infiltration in the tumor microenvironment between the high- and low-risk groups. The highest expression of the OSMTS was detected in hepatocytes at the single-cell transcriptome level. Hepatocytes in the high- and low-risk groups differed significantly in terms of biological function and intercellular communication. Moreover, at the spatial transcriptome level, high expression of OSMTS was mainly in regions enriched in hepatocytes and B cells. Potential drugs targeting specific risk subgroups were identified. Our study revealed that the OSMTS can serve as a promising tool for prognosis prediction and precise intervention in HCC patients.

Associations between the oxidative balance score and constipation: a cross-sectional study of the NHANES, 2005-2010.

OBJECTIVE: The oxidative balance score (OBS) reflects the overall burden of oxidative stress in an individual, with a higher OBS indicating greater antioxidant exposure. This study aimed to explore the association between constipation and OBS. METHODS: Variables were extracted from participants who completed a constipation questionnaire as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The OBS was developed based on dietary and lifestyle factors, encompassing 16 nutrients and 4 lifestyle variables. Weighted logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the association between OBS and constipation. RESULTS: After adjusting for all covariates, weighted multivariate logistic regression analysis revealed a 4% reduction in the incidence of constipation for each additional unit of OBS (OR: 0.96, 95% CI: 0.95-0.97, p < 0.001). In the OBS subgroup, the risk of constipation significantly decreased compared to that in the lowest quartile (Q2: 0.72, P = 0.024; Q3: 0.59, P < 0.001; Q4: 0.54, P < 0.001). CONCLUSIONS: The present study demonstrated a significant association between constipation and the oxidative balance score (OBS), particularly dietary OBS, and that an increase in OBS may reduce the risk of developing constipation, in which oxidative stress may play an important role. This finding suggested that dietary modification could be an important approach for preventing constipation.

Altered hypoxia-induced cellular responses and inflammatory profile in lung fibroblasts from COPD patients compared to control subjects.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators. METHODS: In this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-ß1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA. RESULTS: Hypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-ß significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFß1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects. CONCLUSION: These results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.

Oxidative stress and type 2 diabetes: the development and the pathogenesis, Jordanian cross-sectional study.

Accumulation of reactive oxygen species (ROS) can disrupt the antioxidant defense system, leading to oxidative stress that leads to pathological damage to vital human organs, including hormone-producing glands. Normal physiological function is subsequently disrupted and disorders such as Type 2 Diabetes Mellitus (T2DM) may develop. The critical role of the antioxidant defense system in counteracting ROS and mitigating oxidative stress is fundamental to understanding the pathogenesis of T2DM. In our study, we monitored the oxidant/antioxidant status in a selected Jordanian population to further elucidate this relationship. Our results show higher serum levels of Malondialdehyde (MDA); 0.230 ± 0.05 and 0.207 ± 0.06 µmol/l for the diabetic and the obese groups, respectively, relative to 0.135 ± 0.04 µmol/l for the non-obese healthy group. Lower activity of Catalase (CAT) was recorded among the diabetic (9.2 ± 3.2) and obese groups (11.0 ± 2.8), compared to the non-obese healthy group (12.1 ± 3.5). Significant elevations (P < 0.05) were observed in uric acid concentrations in diabetic and obese subjects: 451 ± 57 mg/dl and 430 ± 51, respectively, versus 342 ± 57 mg/dl in the non-obese healthy group. Moreover, no significant differences were obtained between all the studied groups for the serum albumin and total protein concentrations. Our findings demonstrate the potential role of oxidative stress in the development and occurrence of T2DM.

Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.

Aging represents a complex biological progression affecting the entire body, marked by a gradual decline in tissue function, rendering organs more susceptible to stress and diseases. The human heart holds significant importance in this context, as its aging process poses life-threatening risks. It entails macroscopic morphological shifts and biochemical changes that collectively contribute to diminished cardiac function. Among the numerous pivotal factors in aging, mitochondria play a critical role, intersecting with various molecular pathways and housing several aging-related agents. In this comprehensive review, we provide an updated overview of the functional role of mitochondria in cardiac aging.

Ferroptosis as an emerging target in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobin disorder marked by red blood cell sickling, resulting in severe anemia, painful episodes, extensive organ damage, and shortened life expectancy. In SCD, increased iron levels can trigger ferroptosis, a specific type of cell death characterized by reactive oxygen species (ROS) and lipid peroxide accumulation, leading to damage and organ impairments. The intricate interplay between iron, ferroptosis, inflammation, and oxidative stress in SCD underscores the necessity of thoroughly understanding these processes for the development of innovative therapeutic strategies. This review highlights the importance of balancing the complex interactions among various factors and exploitation of the knowledge in developing novel therapeutics for this devastating disease.

Lycium ruthenicum water extract preserves retinal ganglion cells in chronic ocular hypertension mouse models.

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

The interactive effect of seven weeks aerobic exercise training and piperine against paraquat-induced lung damage in male Wistar rats: Investigating role of oxidative and inflammatory indices.

We aimed to evaluate the effects of seven weeks of aerobic exercise training and piperine on paraquat-induced lung damage. Forty-eight male Wistar rats (230 g, six-eight weeks old) were randomly divided into six groups (n = 8): sham, paraquat (5 mg/kg three times a week; intraperitoneally), paraquat + piperine (10 mg/kg/day; orally), paraquat + aerobic exercise training, paraquat + piperine + aerobic exercise training; and paraquat + vitamin E (20 mg/kg/day; orally) as a positive control. Rats were sacrificed on day 50, and both lung tissues were isolated to measure oxidative (MDA), anti-oxidative (GSH), inflammatory (TNF-α), anti-inflammatory (IL-10) markers, and histological evaluations (hematoxylin-eosin staining). The results of the present study revealed that paraquat significantly decreased body weight, GSH, GSH/MDA ratio, IL-10, and IL-10/TNF-α ratio while increasing MDA, TNF-α, and histopathological damage in lung tissue (P < 0.01 to 0.001). In contrast, treatment with all four interventions meaningfully diminished oxidative, inflammatory markers, and histopathological damage while propagating body weight, anti-oxidative and anti-inflammatory markers following the paraquat-induced lung damage (P < 0.05 to P < 0.001). Interestingly, piperine and piperine + exercise training possessed stronger protective effects against paraquat-induced lung damage than exercise training alone (P < 0.01 to 0.001). Treatment with piperine, exercise training, piperine + exercise training, and vitamin E significantly ameliorated paraquat-induced lung damage. Interestingly, the piperine and piperine + exercise training had more protective effects than other groups. Therefore, piperine and the combination of piperine and exercise training may be valuable candidates for preventing lung injuries.

High-Intensity Interval Training Ameliorates Tramadol-Induced Nephrotoxicity and Oxidative Stress in Experimental Rats.

INTRODUCTION: Tramadol (TRA) is an opioid analgesic widely prescribed for moderate-to-severe pain; however, its abuse and chronic use have been associated with kidney damage. Considering the protective role of exercise training in reducing organ damage, this study aimed to assess the influence of high-intensity interval training (HIIT) on a male rat's kidney following chronic TRA administration. METHODS: In this experimental study, 30 male Wistar rats were assigned to the following groups: control (CON; animals received normal saline five days a week in the first month and three days a week in the second month), exercise (EXE; animals conducted HIIT training according to exercise protocol five days a week for two months), TRA (animals received TRA 50 mg/kg (i.p.) as described for the CON group), EXE-TRA (animals received TRA and conducted exercise protocol), and EXE-SL (animals received normal saline and conducted exercise protocol). Then, serum IL-6 and IL-10 levels, tissue malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and levels of albumin, urea, and creatinine (CR), along with pathological changes in the kidney, were measured. A p-value of <0.05 was considered significant using GraphPad Prism v.9 (GraphPad Software, La Jolla, California, USA). RESULTS: The inflammatory cytokines IL-6 and IL-10 were significantly increased in the EXE and EXE-TRA groups compared to the TRA group. Chronic administration of TRA in the TRA group decreased antioxidant indicators TAC, GPx, and SOD in kidney tissue while increasing oxidative stress MDA compared to the CON group (p<0.05). In contrast, the EXE-TRA group showed higher levels of TAC, GPx, and SOD, while MDA decreased compared to the TRA group. Additionally, serum levels of urea and CR were increased in the TRA group compared to the CON group, whereas these levels were decreased in the EXE-TRA group compared to the TRA group. The inflammatory effect of HIIT training, due to severe hyperemia and mild inflammatory cell infiltration, was seen in all EXE groups. Pathological findings confirmed TRA-induced kidney damage through moderate hyaline cast presence and severe apoptosis in the TRA group. Other findings were in line with the above results. CONCLUSION: These findings confirm the nephrotoxicity of chronic use of TRA through biochemical and oxidative markers and pathological outcomes. In addition, the result suggests that HIIT has the potential to mitigate the detrimental effects of TRA through reversing biochemical and oxidative markers, including TRA-induced apoptosis. Consequently, considering its restorative properties, HIIT could be explored as a prospective nephroprotective approach for long-term TRA treatment.

An analysis of oxidative stress indices and clinical parameters in budgerigars (Melopsittacus undulatus) treated with medetomidine-ketamine and midazolam-ketamine.

Various companion birds, including budgerigars, are anesthetized with injectable anesthesia. The current study aimed to evaluate oxidative stress indices including malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) along with clinical parameters such as the time required to induce, maintain and recover from medetomidine-ketamine anesthesia and midazolam-ketamine anesthesia in budgerigars. Among 20 mature and healthy budgerigars, three groups were assigned as follows: Control (n = 4) to determine baseline oxidative stress indices medetomidine + ketamine (n = 8) anesthetized by intramuscular injections of medetomidine (0.04 mg kg-1) and ketamine (30.00 mg kg-1) in the pectoral muscles, midazolam + ketamine (n = 8) anesthetized by intramuscular injections of midazolam (1.00 mg kg-1) and ketamine (50.00 mg kg-1). Half of birds (n = 4) in the second and third groups were euthanized by cervical dislocation 1 hr after anesthesia induction, blood samples were collected directly from the heart, and sera were extracted. Additionally, the remaining birds were euthanized 24 hr later, and their serum was analyzed for oxidative stress indices. Clinical parameters were recorded during the study. Compared to the medetomidine + ketamine group, the midazolam + ketamine group experienced shorter induction, anesthetic, and recovery times. Administering medetomidine and ketamine elevated TOS levels compared with midazolam + ketamine. No significant difference was found between the test groups for TAC, MDA, or OSI. Therefore, the midazolam + ketamine regimen appears superior to medetomidine + ketamine when performing minor surgeries on budgerigars.

Effects of Different Cow-Milk Beta-Caseins on the Gut-Brain Axis: A Narrative Review of Preclinical, Animal, and Human Studies.

The gut and brain communicate through bidirectional neural, endocrine, and immune signals to coordinate central nervous system activity with gastrointestinal function. Dysregulated inflammation can promote immune cell activation and increase entero-endocrine signaling and intestinal permeability; hence, a functional gut-brain axis is necessary for a healthy digestive system. The consumption of milk products can lead to gut discomfort via effects on gastrointestinal tract function and the inflammatory state, which, in turn, affect the brain. A1 ß-casein and A2 ß-casein are major components of bovine-milk protein, and their digestion may result in different physiological effects following the consumption of milk products. Peptides derived from A1 ß-casein, such as ß-casomorphins, may increase gut dysfunction and inflammation, thereby modulating the availability of bioactive metabolites in the bloodstream and contribute to changes in cognitive function. This narrative review examines the functional interrelationships between the consumption of cow-milk-derived ß-caseins and their effect on the brain, immune system, and the gut, which together comprise the gut-brain axis.

The impact of hydrogen inhalation therapy on blood reactive oxygen species levels: A randomized controlled study.

Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 h. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.

Anti-oxidative stress and cognitive improvement of a semi-synthetic isoorientin-based GSK-3ß inhibitor in rat pheochromocytoma cell PC12 and scopolamine-induced AD model mice via AKT/GSK-3ß/Nrf2 pathway.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive deficits. Although the pathogenesis of AD is unclear, oxidative stress has been implicated to play a dominant role in its development. The flavonoid isoorientin (ISO) and its synthetic derivatives TFGF-18 selectively inhibit glycogen synthase kinase-3ß (GSK-3ß), a potential target of AD treatment. PURPOSE: To investigate the neuroprotective effect of TFGF-18 against oxidative stress via the GSK-3ß pathway in hydrogen peroxide (H2O2)-induced rat pheochromocytoma PC12 cells in vitro and scopolamine (SCOP)-induced AD mice in vivo. METHOD: The oxidative stress of PC12 cells was induced by H2O2 (600 µM) and the effects of TFGF-18 (2 and 8 µM) or ISO (12.5 and 50 µM) were observed. The AD mouse model was induced by SCOP (3 mg/kg), and the effects of TFGF-18 (2 and 8 mg/kg), ISO (50 mg/kg), and donepezil (DNP) (3 mg/kg) were observed. DNP, a currently accepted drug for AD was used as a positive control. The neuronal cell damages were analyzed by flow cytometry, LDH assay, JC-1 assay and Nissl staining. The oxidative stress was evaluated by the detection of MDA, SOD, GPx and ROS. The level of ACh, and the activity of AChE, ChAT were detected by the assay kit. The expressions of Bax, Bcl-2, caspase3, cleaved-caspase3, p-AKT (Thr308), AKT, p-GSK-3ß (Ser9), GSK-3ß, Nrf2, and HO-1, as well as p-CREB (Ser133), CREB, and BDNF were analyzed by western blotting. Morris water maze test was performed to analyze learning and memory ability. RESULTS: TFGF-18 inhibited neuronal damage and the expressions of Bax, caspase3 and cleaved-caspase3, and increased the expression of Bcl-2 in vitro and in vivo. The level of MDA and ROS were decreased while the activities of SOD and GPx were increased by TFGF-18. Moreover, TFGF-18 increased the p-AKT, p-GSK-3ß (Ser9), Nrf2, HO-1, p-CREB, and BDNF expression reduced by H2O2 and SCOP. Meanwhile, MK2206, an AKT inhibitor, reversed the effect of TFGF-18 on the AKT/GSK-3ß pathway. In addition, the cholinergic system (ACh, ChAT, and AChE) disorders were retrained and the learning and memory impairments were prevented by TFGF-18 in SCOP-induced AD mice. CONCLUSIONS: TFGF-18 protects against neuronal cell damage and cognitive impairment by inhibiting oxidative stress via AKT/GSK-3ß/Nrf2 pathway.

The flavonoid fisetin reduces multiple physiological risk factors for dementia.

Dementia is a growing problem around the globe as the world's population continues to age. Multiple studies have identified potentially modifiable risk factors for the development of dementia suggesting that addressing some or all of these risk factors might have a significant impact on the aging population worldwide. However, this is not always as straightforward as it seems since many of these risk factors are currently treated with drugs specific to the risk factor. Moreover, since people can have multiple risk factors, addressing each of them individually could be highly problematic as it would likely lead to negative outcomes associated with polypharmacy and, in the long term, could do significant harm. A potential alternative is to identify compounds that have shown efficacy against a number of these different risk factors. As discussed in this review, there is strong evidence that the flavonol fisetin is one such compound. In animal studies it has shown efficacy against many of the risk factors that have been associated with an increased risk of developing dementia and also exhibits direct neuroprotective effects. Thus, further human research on fisetin in the context of dementia risk factors is clearly warranted.

Tenuazonic acid-induced mycotoxicosis in an immunosuppressed mouse model and its prophylaxis with cinnamaldehyde.

Patients with impaired immune systems are particularly vulnerable to infections. With the increasing number of immunocompromised patients, it becomes necessary to design studies that evaluate the effects of toxic contaminants that are a part of our daily lives. Simultaneously, the management of these toxic components also becomes essential. Therefore, the present study evaluated the possible protective role of cinnamaldehyde (Cin) against tenuazonic acid-induced mycotoxicosis in the immunosuppressed murine model. Tenuazonic acid (TeA), a toxin usually produced by Alternaria species, is a common contaminant in tomato and tomato-based products. Evaluating the potential toxicity of a hazardous chemical necessitates the use of in vitro, in vivo, and in silico methods. Here, the immunomodulatory effect of TeA was assessed in vitro using mouse splenocytes. In silico docking was carried out for the tumour markers of eight organs and TeA. The haematological, histopathological, and biochemical aspects were analysed in vivo. The sub-chronic intoxication of mice with TeA showed elevated malondialdehyde, reduced catalase, and superoxide dismutase production, along with abnormal levels of aspartate aminotransferase and alanine transaminase. The treatment with Cin prevented TeA-induced alterations of antioxidant defense enzyme activities and significantly forbade TeA-induced organ damage, showing therapeutic effects and toxicity reduction in TeA-induced mycotoxicosis.

Natural polysaccharides as promising reno-protective agents for the treatment of various kidney injury.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.