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Background and Objectives: Oxidative stress resulting from a disturbance of the endogenous redox system is suspected in numerous diseases of the central nervous system, including epilepsy. In addition, antiseizure medications (ASMs), especially those of the old generation, may further increase oxidative stress. To evaluate the effects of ASM generation on oxidative stress, we conducted a cross-sectional study in patients with epilepsy treated with old, new, and polytherapy. Materials and Methods: The antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as the concentrations of malondialdehyde, protein carbonyl, nitrate, nitrite, and glutathione in reduced and oxidized forms, were measured in 49 patients with epilepsy and 14 healthy controls. In addition, the plasma concentrations of ASMs and metabolites of carbamazepine and valproic acid were measured in the patients. Results: Patients with epilepsy showed increased activities of superoxide dismutase and catalase (p < 0.001), concentrations of glutathione disulfide and markers of nitric oxide metabolism (p < 0.001), and decreased activities of glutathione peroxidase, glutathione reductase, glutathione, and nitrite concentrations (p ≤ 0.005) compared to healthy controls. A comparison of ASM generations revealed increased levels of superoxide dismutase and catalase (p ≤ 0.007) and decreased levels of glutathione peroxidase and glutathione reductase (p ≤ 0.01) in patients treated with old ASMs compared to those treated with new generation ASMs. In addition, an increase in protein carbonyl and nitric oxide metabolites (p ≤ 0.002) was observed in patients treated with old generation ASMs compared to those treated with new generation ASMs. Most oxidative stress parameters in patients receiving polytherapy with ASMs were intermediate between the results of patients treated with the old and new generations of ASMs. Conclusions: An increase in oxidative stress markers and modulation of antioxidant enzyme activities was observed in patients with epilepsy compared to controls. The results of our study showed significantly higher oxidative stress in patients treated with old ASMs compared to those treated with new generation ASMs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). Methods: A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). Results: Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. Conclusions: This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals. [ABSTRACT FROM AUTHOR]

The objectives of this study were to explore the role that eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) plays in heart failure (HF), highlighting the potential connection to oxidative stress pathways. Following PRISMA guidelines, we conducted electronic searches of the literature in MEDLINE and EMBASE focusing on serum EPA and/or DHA and EPA and/or DHA supplementation in adult patients with heart failure or who had heart failure as an outcome of this study. We screened 254 studies, encompassing RCTs, observational studies, and cohort studies that examined HF outcomes in relation to either serum concentrations or dietary supplementation of EPA and/or DHA. The exclusion criteria were pediatric patients, non-HF studies, abstracts, editorials, case reports, and reviews. Eleven studies met our criteria. In meta-analyses, high serum concentrations of DHA were associated with a lower rate of heart failure with a hazard ratio of 0.74 (CI = 0.59–0.94). High serum concentrations of EPA also were associated with an overall reduction in major adverse cardiovascular events with a hazard ratio of 0.60 (CI = 0.46–0.77). EPA and DHA, or n3-PUFA administration, were associated with an increased LVEF with a mean difference of 1.55 (CI = 0.07–3.03)%. A potential explanation for these findings is the ability of EPA and DHA to inhibit pathways by which oxidative stress damages the heart or impairs cardiac systolic or diastolic function producing heart failure. Specifically, EPA may lower oxidative stress within the heart by reducing the concentration of reactive oxygen species (ROS) within cardiac tissue by (i) upregulating nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of antioxidant enzyme activity, including heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain, and manganese superoxide dismutase (SOD), (ii) increasing the expression of copper–zinc superoxide dismutase (MnSOD) and glutathione peroxidase, (iii) targeting Free Fatty Acid Receptor 4 (Ffar4), (iv) upregulating expression of heme-oxygenase-1, (v) lowering arachidonic acid levels, and (vi) inhibiting the RhoA/ROCK signaling pathway. DHA may lower oxidative stress within the heart by (i) reducing levels of mitochondrial-fission-related protein DRP-1(ser-63), (ii) promoting the incorporation of cardiolipin within the mitochondrial membrane, (iii) reducing myocardial fibrosis, which leads to diastolic heart failure, (iv) reducing the expression of genes such as Appa, Myh7, and Agtr1α, and (v) reducing inflammatory cytokines such as IL-6, TNF-α. In conclusion, EPA and/or DHA have the potential to improve heart failure, perhaps mediated by their ability to modulate oxidative stress. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AbstractNuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor that activates antioxidant genes and increases detoxifying enzymes. Studies have shown that dietary compounds can activate the Nrf2 expression and improve the antioxidant response in patients with exacerbated oxidative stress, such as chronic kidney disease (CKD). We aimed to evaluate the efficacy of nutritional interventions on Nrf2 expression and phase II antioxidant enzymes in clinical trials in CKD. We searched PubMed, Lilacs, Embase, Scopus, and Cochrane Library databases of published clinical trials and the Cochrane tool was used for the quality assessment of the studies included. We reported this review according to the PRISMA and it was registered in PROSPERO (42023389619). Thirty-nine studies were included in this review; nine evaluated the Nrf2 expression and three showed an increase in its expression. Twenty-three studies found an increase in the antioxidant enzyme levels, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, a high risk of bias was found in most of the studies and high heterogeneity in the designs, type, and duration of supplementation administered. These results suggest that dietary supplementations have a promising effect on the antioxidant enzyme response, however, it is recommended that further studies should be carried out. [ABSTRACT FROM AUTHOR]

Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo. [ABSTRACT FROM AUTHOR]

Ferroptosis plays important roles both in normal physiology and multiple human diseases. It is well known that selenoprotein named glutathione peroxidase 4 (GPX4) is a crucial regulator for ferroptosis. However, it remains unknown whether other selenoproteins responsible for the regulation of ferroptosis, particularly in gut diseases. In this study, it is observed that Selenoprotein I (Selenoi) prevents ferroptosis by maintaining ether lipids homeostasis. Specific deletion of Selenoi in intestinal epithelial cells induced the occurrence of ferroptosis, leading to impaired intestinal regeneration and compromised colonic tumor growth. Mechanistically, Selenoi deficiency causes a remarkable decrease in ether‐linked phosphatidylethanolamine (ePE) and a marked increase in ether‐linked phosphatidylcholine (ePC). The imbalance of ePE and ePC results in the upregulation of phospholipase A2, group IIA (Pla2g2a) and group V (Pla2g5), as well as arachidonate‐15‐lipoxygenase (Alox15), which give rise to excessive lipid peroxidation. Knockdown of PLA2G2A, PLA2G5, or ALOX15 can reverse the ferroptosis phenotypes, suggesting that they are downstream effectors of SELENOI. Strikingly, GPX4 overexpression cannot rescue the ferroptosis phenotypes of SELENOI‐knockdown cells, while SELENOI overexpression can partially rescue GPX4‐knockdown‐induced ferroptosis. It suggests that SELENOI prevents ferroptosis independent of GPX4. Taken together, these findings strongly support the notion that SELENOI functions as a novel suppressor of ferroptosis during colitis and colon tumorigenesis. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of cell death, distinct from apoptosis, necrosis, and autophagy, and is characterized by altered iron homeostasis, reduced defense against oxidative stress, and increased lipid peroxidation. Extensive research has demonstrated that ferroptosis plays a crucial role in the treatment of gynecological malignancies, offering new strategies for cancer prevention and therapy. However, chemotherapy resistance poses an urgent challenge, significantly hindering therapeutic efficacy. Increasing evidence suggests that inducing ferroptosis can reverse tumor resistance to chemotherapy. This article reviews the mechanisms of ferroptosis and discusses its potential in reversing chemotherapy resistance in gynecological cancers. We summarized three critical pathways in regulating ferroptosis: the regulation of glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways, considering their prospects and challenges as strategies to reverse chemotherapy resistance. These studies provide a fresh perspective for future cancer treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Over the last decade, extensive use of coccidiostats to treat and control Eimeria infection has developed drug resistance, prompting the search for new alternative therapies. Rhatany is proven to have various pharmacological properties. Objective: The present study aimed to in vitro and in vivo evaluate the effect of Rhatany roots extract (RRE) as an anti-eimerial and anti-apoptotic agent against murine eimeriosis induced by Eimeria papillata. Methods: Phytochemical screening by gas chromatography-mass spectrometry analysis (GC-MS) was used to detect active compounds in RRE. In vitro anti-eimerial activity of RRE (200, 100, 50 mg/ml), amprolium, phenol, Dettol™, and formalin were studied after incubation with non-sporulated Eimeria oocysts. For the in vivo study, twenty-five male C57BL/6 mice were randomly allocated into five groups. Animals in the first group were just given distilled H2O, while those in the second group were given 200 mg/kg RRE for 5 days. The Eimeria parasite’s oocysts were infected into the third, fourth, and fifth groups. For treatment, RRE (200 mg/kg) and amprolium (120 mg/kg) were orally given to the 4th and 5th groups for five days, respectively. All mice were euthanized, on day 5 post-infection, to collect the jejunal tissues under study. Investigations were undertaken into the oocyst output in feces and goblet cells in mice jejuna. Assays for glutathione peroxidase (GPx), hydrogen peroxide (H2O2), and myeloperoxidase (MPO) were also performed. In jejunal tissue, cysteine aspartic acid protease-3 (Caspase-3) was counted using immunohistochemistry, while BCL2-associated X protein (Bax) and B-cell lymphoma-2 (BCL-2) were assayed using ELISA. In addition, mRNA expression of the goblet cell response gene (MUC2) was detected using real-time PCR. Results: Phytochemical screening by GC-MS demonstrated the presence of 22 compounds in the RRE. The in vitro study revealed that RRE significantly inhabited the oocyst sporulation in a dose-dependent manner. By day 5 after infection with the Eimeria parasite, the number of oocysts in mice feces was significantly reduced after RRE treatment (1.308 × 106 ± 1.36 × 105 oocysts/g feces) compared to the infected group (5.387 × 106 ± 4.29 × 105 oocysts/g feces). Moreover, the Eimeria infection reduced the number of goblet cells of mice jejuna and its specific gene, MUC2. The treatment with RRE increased the number of goblet cells/villus from 3.45 ± 0.17 to 6.04 ± 0.23, associated with upregulation for MUC2 from 0.26 to 2.39-fold. Also, the Eimeria experimental infection lowered the activity of the antioxidant enzyme represented by GPx (23.99 ± 3.68 mg/g tissue), while increasing the stress parameters of hydrogen peroxide (0.07 ± 0.01 mM/g) as well as the activity of MPO (66.30 ± 3.74 U/mg). The production of apoptotic markers including Caspase-3 (68.89 ± 2.67 U/g) and Bax (159.05 ± 6.50 pg/ml) was significantly elevated while decreasing the anti-apoptotic marker of BCL2 (0.42 ± 0.07 pg/ml). Our study proved that RRE significantly reduced oxidative stress, and apoptotic markers as well as the inflammatory activity of MPO. Also, antioxidant enzyme and anti-apoptotic activity in the jejunum of E. papillata-infected mice were enhanced after RRE treatment. Conclusion: Our study highlights the potential of RRE as a natural solution for coccidiosis management by modulating apoptosis in E. papillata host cells. However, further research is needed to fully understand the underlying mechanisms and enhance our understanding of its therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties—particularly its phenolic and flavonoid constituents—that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group’s normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis. [ABSTRACT FROM AUTHOR]

Estramustine (EM), a clinically successful hormone‐refractory anti‐prostate cancer drug, exhibited potent anti‐proliferative activity, depolymerized microtubules, blocked cells at mitosis, and induced cell death in different cancer cells. Altered iron metabolism is a feature of cancer cells. Using EM, we examined the plausible relationship between microtubule depolymerization and induction of ferroptosis in human neuroblastoma (SH‐SY5Y and IMR‐32) cells. EM reduced glutathione (GSH) levels and induced reactive oxygen species (ROS) generation. The pre‐treatment of neuroblastoma cells with ROS scavengers (N‐acetyl cysteine and dithiothreitol) reduced the anti‐proliferative effects of EM. EM treatment increased labile iron pool (LIP), depleted glutathione peroxidase 4 (GPX4) levels, and lipid peroxidation, hallmark features of ferroptosis, highlighting ferroptosis induction. Ferroptosis inhibitors (deferoxamine mesylate and liproxstatin‐1) abrogated the cytotoxic effects of EM, further confirming ferroptosis induction. Vinblastine and nocodazole also increased LIP and induced lipid peroxidation in neuroblastoma cells. This study provides evidence for the coupling of microtubule integrity to ferroptosis. The results also suggest that microtubule‐depolymerizing agents may be considered for developing pro‐ferroptosis chemotherapeutics. [ABSTRACT FROM AUTHOR]

Many microbes accumulate energy storage molecules such as triglycerides (TAG) and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen-limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study, we show that reactive oxygen species (ROS) actively accumulate during nitrogen limitation in the microalga Chlorella sorokiniana. Accumulation of ROS is mediated by the downregulation of genes encoding ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and by the upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase, and amine oxidases. The expression of genes involved in ascorbate and glutathione metabolism is also affected under this condition. ROS accumulation contributes to the degradation of monogalactosyl diacylglycerol (MGDG) and thylakoid membrane remodeling, leading to chlorosis. Quenching ROS under nitrogen limitation reduces the degradation of MGDG and the accumulation of TAG. This work shows that ROS accumulation, membrane remodeling, and TAG accumulation under nitrogen limitation are intricately linked in the microalga C. sorokiniana. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE: To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroidinduced osteonecrosis of the femoral head. METHODS: General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head. In addition, six femoral head specimens were collected from these patients. According to the Association Research Circulation Osseous (ARCO) staging system, serum specimens were grouped into ARCO II, III, and IV, while femoral head specimens were classified into ARCO III and IV. Serum levels of malondialdehyde and superoxide dismutase 1 were measured. The protein expression of superoxide dismutase 1, glutathione peroxidase 4, Bcl-2 in the femoral head was detected and verified by Data independent acquisition (DIA) for quantitative sequencing, western blot and alkaline phosphate detection. RESULTS AND CONCLUSION: The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age, sex and necrotic side. The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage III compared with those with ARCO stage II and IV. The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox. The levels of superoxide dismutase 1, glutathione peroxidase 4, and Bcl-2 in the necrotic region were lower than in the normal region, as well as lower in ARCO stage IV than in ARCO stage III. Western blot verified the results of DIA protein quantification. The alkaline phosphatase activity was lower in the necrotic region than in the normal region, as well as lower in ARCO stage IV than in ARCO stage III. In the necrotic and sclerotic regions, the function of differential proteins was also related to redox, and superoxide dismutase 1, glutathione peroxidase 4, Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region, as well as lower in ARCO stage IV than in ARCO stage III. To conclude, glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels, inducing osteoblast ferroptosis, and inhibiting osteogenic function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury. 3-Nitro-Nmethylsalicylamide (3-NNMS) can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury, but there is no clear research and clinical application. OBJECTIVE: To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS: Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group, 0, 25 and 125 μg/mL 3-NNMS groups, with 10 rats in each group. Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups. 3-NNMS was injected into the injury site 30 minutes before reperfusion. The animals were sacrificed 2 hours after reperfusion. Blood from the apical part of the heart, and the tissue of the rectus femoris muscle of the right lower limb were taken for testing. The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining. Serum levels of creatine kinase found in the skeletal muscle (CK-MM), lactate dehydrogenase, and myeloperoxidase were detected using ELISA; the levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde, reactive oxygen species, superoxide dismutase, catalase and glutathione peroxidase in the rectus femoris muscle were measured; and adenosine triphosphate (ATP) level, ATPase activity, and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION: Compared with the control group, the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase, increased levels of nuclear factor κB, tumor necrosis factor α, interleukin 1β, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle, and reduced ATPase activity and mitochondrial respiratory control rate. Moreover, cell morphology was irregular, inflammatory cell infiltration was obvious, and the cells were swollen in rats after ischemia-reperfusion injury. Compared with the 0 μg/mL group, the serum CK-MM and lactate dehydrogenase levels decreased, the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased, reactive oxygen species level decreased, and superoxide dismutase activity increased in the 25 μg/mL group; cell morphology was more regular, inflammatory cell infiltration was lighter, and cell swelling was alleviated. Compared with the 0 μg/mL group, the 125 μg/mL group had a reduction in the serum levels of CK-MM, lactate dehydrogenase, and myeloperoxidase and the levels of nuclear factor κB, tumor necrosis factor α, cyclooxygenase 2, malondialdehyde and reactive oxygen species in the rectus femoris muscle, as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle, and mitochondrial respiratory control rate. Moreover, the cells were arranged neatly, the outline was clear and complete, and the inflammatory cell infiltration was light. To conclude, 3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion, and its mechanism of action may be through improving mitochondrial function, reducing reactive oxygen species production, decreasing oxidative stress and inflammatory response, and thus reducing tissue damage and repairing skeletal muscle function. [ABSTRACT FROM AUTHOR]

The experiment aimed to investigate the effects of high sugar supplementation on the growth performance, serum biochemical, and antioxidant indexes of perinatal yaks. Select 16 healthy and approximately 200 kg female yaks during the perinatal period, and randomly divide them into two groups, with eight replicates per group and one yak per replicate. The control group was fed with basic feed, while the experimental group was supplemented with 1.25 g/(kg·d) high sugar feed on top of the basic feed. The pre trial period was seven days, and the main trial period starts from the 21st day before delivery and ends on the 28th day after delivery. Compared with the control group, the average daily weight gain (ADG) of yaks in the experimental group was significantly increased (P<0.05). Compared with the control group, on the 14th day before delivery, the serum glutathione peroxidase (GSH-Px) activity in yaks was extremely increased (P<0.01). Compared with the control group, on the 7th day before delivery, the levels of growth hormone (GH), urea nitrogen (BUN), alkaline phosphatase (ALP), GSH-Px, and total antioxidant capacity (T-AOC) in yak serum were extremely increased (P<0.01), while the activity of superoxide dismutase (SOD) in yak serum was significantly reduced (P<0.05). Compared with the control group, on the day of delivery, the serum levels of GH, BUN, glucose (GLU), ALP, and GSH-Px in yaks were extremely increased (P<0.01), while the activity of aspartate aminotransferase (AST) in yak serum was extremely reduced (P<0.01). The levels of estrogen (E2) and progesterone (P4) in yak serum were significantly increased (P<0.05). Compared with the control group, on the 7th day postpartum, the levels of GH, BUN, GLU, cholesterol (TC), phosphorus (P), GSH-Px, and T-AOC in yak serum were extremely increased (P<0.01), while the levels of AST, malondialdehyde (MDA), and SOD in yak serum were extremely reduced (P<0.01), and the activity of ALP in yak serum was significantly increased (P<0.05). Compared with the control group, on the 14th day after delivery, the levels of GH, albumin (ALB), TC, and P in yak serum extremely increased (P<0.01), while the AST activity in yak serum significantly decreased (P<0.05). Compared with the control group, on the 21st day postpartum, the serum GH content in yaks extremely increased (P<0.01), and the serum TC content in yaks significantly increased (P<0.05). The study indicates that high sugar supplementation can improve the growth performance and antioxidant capacity of yaks during the perinatal period. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, the escalating prices of feedstuff resources have posed significant challenges to animal husbandry, necessitating the creation of innovative approaches to mitigate its effects. GAA (also known as N-amidinoglycine) serves as the sole precursor for creatine synthesis. GAA could enhance growth performance and regulate fat deposition to improve meat quality. Current studies on GAA mainly center on pigs and chickens, with limited reports on its effects on sheep. In our study, we used weaned Hu sheep as subjects. We aimed to explore the impact of dietary GAA supplementation on production performance, serum biochemistry, meat quality and rumen fermentation. This study provides a theoretical foundation for utilizing GAA in sheep meat production. Our findings indicate that GAA enhances growth performance, rumen fermentation and fat accumulation. In addition, GAA might enhance the quality of sheep meat, which presents a promising prospect for meat sheep breeding. Guanidinoacetic acid (GAA) can effectively improve the metabolism of energy and proteins by stimulating creatine biosynthesis. We present a study exploring the impact of GAA on production performance, serum biochemistry, meat quality and rumen fermentation in Hu sheep. A total of 144 weaned male Hu sheep (body weight 16.91 ± 3.1 kg) were randomly assigned to four groups with three replicates of twelve sheep in each group. The diets were supplemented with 0 (CON), 500 (GAA−1), 750 (GAA−2) and 1000 mg/kg (GAA−3) of GAA (weight of feed), respectively. After a comprehensive 90-day experimental period, we discovered that the supplementation of GAA had a remarkable impact on various muscle parameters. Specifically, it significantly enhanced the average daily growth (ADG) of the animals and improved the shear force and fiber diameter of the muscle, while also reducing the drip loss and muscle fiber density. Furthermore, the addition of GAA to the feed notably elevated the serum concentrations of high-density lipoprotein cholesterol (HDL−C), total protein (TP) and globulin (GLB), as well as the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH−Px). Concurrently, there was a decrease in the levels of triglycerides (TG) and malondialdehyde (MDA) in the serum. In addition, GAA decreased the pH and the acetate-to-propionate ratio and increased the total volatile fatty acids (TVFA) and ammoniacal nitrogen (NH3−N) levels of rumen fluid. Additionally, GAA upregulated acetyl-CoA carboxylase (ACC) gene expression in the Hu sheep's muscles. In conclusion, our findings suggest that GAA supplementation not only enhances muscle quality but also positively affects serum biochemistry and ruminal metabolism, making it a potential candidate for improving the overall health and performance of Hu sheep. [ABSTRACT FROM AUTHOR]

Ferroptosis is a type of nonapoptotic cell death that is characteristically caused by phospholipid peroxidation promoted by radical reactions involving iron. Researchers have identified many of the protein factors that are encoded by genes that promote ferroptosis. Glutathione peroxidase 4 (GPX4) is a key enzyme that protects phospholipids from peroxidation and suppresses ferroptosis in a glutathione-dependent manner. Thus, the dysregulation of genes involved in cysteine and/or glutathione metabolism is closely associated with ferroptosis. From the perspective of cell dynamics, actively proliferating cells are more prone to ferroptosis than quiescent cells, which suggests that radical species generated during oxygen-involved metabolism are responsible for lipid peroxidation. Herein, we discuss the initial events involved in ferroptosis that dominantly occur in the process of energy metabolism, in association with cysteine deficiency. Accordingly, dysregulation of the tricarboxylic acid cycle coupled with the respiratory chain in mitochondria are the main subjects here, and this suggests that mitochondria are the likely source of both radical electrons and free iron. Since not only carbohydrates, but also amino acids, especially glutamate, are major substrates for central metabolism, dealing with nitrogen derived from amino groups also contributes to lipid peroxidation and is a subject of this discussion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect and mechanism of Rehmannioside A (ReA) on brain dysfunction in cecal ligation and perforation (CLP) -induced sepsis rats. Methods: 56 CLP-induced sepsis rats were randomly divided into CLP group (n=12), CLP+20ReA group (n=11), CLP+40ReA group (n=11), CLP+80ReA group (n=11), and GPX4-IN-3 group (n=11). Ten rats underwent Sham operation as sham group. Rats in Sham group and CLP group were given 1 mL dimethyl sulfoxide (DMSO). Rats in CLP+20ReA group, CLP+40ReA group and CLP+80ReA group were given 1 mL of 20, 40 and 80 mg/kg/d Rehmannioside A, respectively. Rats in GPX4-IN-3 group were simultaneously administrated with 0.5 mL 80 mg/kg/d of Rehmannioside A and 0.5 mL 15 mg/kg/d of the selective inducer of ferroptosis GPX4-IN-3. Each group was given the drug for 3 days. Neural function score and Morris water maze test were used to evaluate brain function. Neuron-specific enolase (NSE) and S100β levels were detected by ELISA. The water content of brain tissue was measured by weighing method. Brain injury was evaluated by HE staining and Nissl staining. The levels of reduced glutathione (GSH) and malondialdehyde (MDA) in brain tissue were detected by micromethods. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The content of Fe2+ in brain tissue was determined by micromethod. The levels of nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH related protein 1 (Keap1) and glutathione peroxidase 4 (GPX4) protein in brain tissue were detected by Western blot. Results: Compared with CLP group, the neural function scores and escape latency of CLP+20ReA group, CLP+40ReA group and CLP+80ReA group decreased (P<0.05), the number of crossing platforms increased (P<0.05), the neuronal damage reduced, the levels of serum NSE and S100β decreased (P<0.05), the level of GSH in brain tissue increased (P<0.05). The water content of brain tissue and levels of MDA, IL-6, TNF-α and the content of Fe2+ in brain tissue decreased(P<0.05), the protein expressions of Nrf2 (nucleus) and GPX4 in brain tissue increased(P<0.05), and the protein expression of Keap1 decreased(P<0.05). Compared with CLP+80ReA group, the brain dysfunction of GPX4-IN-3 group was aggravated, and the Nrf2/GPX4 pathway was inhibited (P<0.05). Conclusion: Rehmannioside A inhibits ferroptosis by activating Nrf2/GPX4 pathway, thereby alleviating brain dysfunction in CLP-induced sepsis rats. [ABSTRACT FROM AUTHOR]

Background: Observational studies have shown that oxidative stress (OS) is associated with Parkinson's disease (PD). However, whether such observations reflect cause-effect remains largely unknown. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal-effects between OS biomarkers and PD. Methods: We selected summary statistics data for single-nucleotide polymorphisms (SNPs) associated with catalase (n = 13), glutathione peroxidases (n = 12), superoxide dismutase (n = 13), vitamin A (n = 7), vitamin C (n = 10), vitamin E (n = 12), vitamin B12 (n = 8), folate (n = 14), copper (n = 6), Zinc (n = 7), and iron (n = 23) levels, and the corresponding data for PD from the International Parkinson Disease Genomics Consortium (IPDGC, 33,674 cases and 449,056 controls). Inverse-variance weighted (IVW) MR analyses were conducted to estimate associations of OS with PD. Reverse MR analysis was further performed to predict the causal effects of PD on the above OS biomarkers. Results: As for PD, the IVW method suggested that the Zinc (Zn) levels was significantly associated with PD (OR = 1.107, 95% CI 1.013-1.211; p = 0.025), which is consistent with results from the weighted median analyses. Moreover, the results remained consistent and robust in the sensitivity analysis. However, there were no significant associations of catalase, glutathione peroxidases, superoxide dismutase, vitamin A, vitamin C, vitamin E, vitamin B12, folate, copper, or iron with PD. As for OS, our reverse MR analysis also did not support a causal effect of liability to PD on OS. Conclusion: The MR study supported the causal effect of Zn on PD. These findings may inform prevention strategies and interventions directed toward OS and PD. [ABSTRACT FROM AUTHOR]

Cisplatin (CIS) is a platinum‐derived chemotherapeutic agent commonly utilized in the treatment of various malignant tumours. However, anticancer doses of the drug cause serious damage to the brain. This study aimed to determine the potential protective effects of tangeretin, which has antioxidant and anti‐inflammatory properties, in cisplatin‐induced neurotoxicity on BALB/c mice brains. Male BALB/c mice were randomized and separated into four groups. Tangeretin was given for 10 days by gavage. CIS was injected as a single dose of 10 mg/kg intraperitoneally (ip) on the 10th day. Brain tissues, malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and nitric oxide (NO) levels were measured to determine oxidative damage and myeloperoxidase, tumour necrosis factor‐alpha (TNF‐α), interleukin 1 beta (IL‐1β), IL‐6 and IL‐10 were measured to determine inflammatory activity. In addition, 8‐OHdG and caspase‐3 were analysed by immunofluorescence methods. While CIS administration remarkably elevated reactive oxygen species, MDA, and NO levels in brain tissue compared to the control, tGSH, GPx, SOD and CAT levels were significantly decreased. Also, it has been detected that TNF‐α, IL‐1β and IL‐6 obtained in CIS‐treated groups increased as well as IL‐10 decreased, thereby elevating the inflammatory response. In addition, 8‐OHdG and caspase‐3 immunoreactivity in neurons increased with CIS administration. Treatment with tangeretin ameliorated the deterioration in oxidant/antioxidant status, overpowered neuroinflammation and ameliorated neurotoxicity‐induced apoptosis. This study shows that tangeretin has beneficial effects on CIS‐induced neurodegeneration. Possible mechanisms underlying these beneficial effects include the antioxidant and anti‐inflammatory properties of tangeretin. [ABSTRACT FROM AUTHOR]

Iron death is considered to be an iron-dependent, non-apoptotic form of regulated cell death, which is mainly triggered by reactive oxygen species (ROS) production and imbalance of iron homeostasis leading to severe lipid peroxidation, and it induces related factors that can directly or indirectly affect glutathione peroxidase through different pathways, leading to decreased antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in the cells, and ultimately leading to oxidative cell death. Meanwhile, iron death is regulated by various pathways, such as iron metabolism, mitochondrial activity, redox homeostasis, and disease-related signalling pathways. It has been reported that dysregulation of iron death metabolic pathways can affect the development and progression of hepatocellular carcinoma. Little is known about the molecular mechanisms by which iron death leads to disease, but iron death-related genes and pathways are associated with hepatocellular carcinoma progression. It was found that abnormal activation of the Wnt/β-catenin signalling pathway is associated with recurrence, invasion, metastasis and immune escape of hepatocellular carcinoma, and is closely linked to iron death. This pathway can further aggravate the progression of hepatocellular carcinoma by regulating the occurrence of iron death. Some substantial progress has been made in this field in hepatocellular carcinoma. Therefore, in the present review, we will explore the process of iron death by outlining its molecular mechanism and its role in hepatocellular carcinoma, and at the same time, we will specifically analyse the Wnt/β-catenin signaling pathway to regulate the process of iron death, so as to provide a reliable scientific theoretical basis for the treatment of hepatocellular carcinoma in the future. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) has the highest fatality rate among all gynecological malignancies, necessitating the exploration of novel, efficient, and low-toxicity therapeutic strategies. Ferroptosis is a type of programmed cell death induced by iron-dependent lipid peroxidation and can potentially activate antitumor immunity. Developing highly effective ferroptosis inducers may improve OC prognosis. Results: In this study, we developed an ultrasonically controllable two-dimensional (2D) piezoelectric nanoagonist (Bi2MoO6-MXene) to induce ferroptosis. A Schottky heterojunction between Bi2MoO6 (BMO) and MXene reduced the bandgap width by 0.44 eV, increased the carrier-separation efficiency, and decreased the recombination rate of electron–hole pairs under ultrasound stimulation. Therefore, the reactive oxygen species yield was enhanced. Under spatiotemporal ultrasound excitation, BMO-MXene effectively inhibited OC proliferation by more than 90%, induced lipid peroxidation, decreased mitochondrial-membrane potential, and inactivated the glutathione peroxidase and cystathionine transporter protein system, thereby causing ferroptosis in tumor cells. Ferroptosis in OC cells further activated immunogenic cell death, facilitating dendritic cell maturation and stimulating antitumor immunity. Conclusion: We have succeeded in developing a highly potent ferroptosis inducer (BMO-MXene), capable of inhibiting OC progression through the sonodynamic-ferroptosis-immunogenic cell death pathway. [ABSTRACT FROM AUTHOR]

Moringa oleifera, a widely recognized plant more commonly known as moringa, has obtained significant research interest in recent years due to its prospective physiological advantages, including its claimed ability to counteract carcinogenesis. The moringa plant has been found to possess bioactive components that exhibit promising anticancer activities against different human cancers, such as breast cancer, prostate cancer, pancreatic cancer, etc. The cytotoxic properties of moringa seed extracts on cancerous cells have also been provided in this paper along with other notable health benefits. The extracts derived from moringa seeds inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways. They also stimulated intracellular reactive oxygen species (ROS) production and subsequently induced caspase‐3 activity. The impact of moringin and avenanthramide 2f on the stimulation of caspases 2, 4, 8, and 9 results in reduction in the proliferation of cancer cells. The results reported by research studies hold significant implications for identifying and targeting specific molecular entities that could serve as potential therapeutic targets in search of effective cancer treatments. Furthermore, the flavonoids in moringa seed can remove mitochondrial reactive oxygen species, protecting beta cells and bringing hyperglycemia under control. M. oleifera seed oil can reduce the risk of cardiovascular diseases via reduced malondialdehyde (MDA) formation and modulation of cardiac superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. This article provides a comprehensive summary of the noteworthy discoveries derived from a rigorous investigation that explored into the impact of moringa seeds on the prevention/reduction of various cancers and other complex diseases. [ABSTRACT FROM AUTHOR]

Background: The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture. Objective: This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system. Methods: Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish's behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET's impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored. Results: The lethal concentration (LC50) of MET estimated using Finney's probit technique was 3.77 mg/L. The fish's behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5–7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5–7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure. Conclusion: According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated. [ABSTRACT FROM AUTHOR]

Marine red yeast is a good feed additive for the aquaculture industry that can promote the growth of aquatic animals, and significantly improve their antioxidant capacity, survival rate, and nonspecific immune ability of the body. Our hypothesis is that dietary supplementation with marine red yeast could affect the serum biochemistry, muscle composition, muscle fatty acid composition, lipid metabolism enzyme activity, and expression of antioxidant and inflammatory genes in juvenile genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Five diets with different levels of marine red yeast (0 %, 0.25 %, 0.50 %, 0.75 %, and 1.00 %) were used to feed juvenile GIFT (initial weight: 21.12 ± 0.86 g) for 60 days. The main results are as follows: Compared with the control group (0 % marine red yeast), the contents of total protein (TP), albumin (ALB), high-density lipoprotein (HDL), and free fatty acid (FFA) in the serum of juvenile GIFT tilapia significantly increased (P < 0.05), while the contents of glucose (GLU), triglyceride (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), alanine aminotransferase (ALT) significantly decreased (P < 0.05). The contents of crude protein, crude fat, and docosahexaenoic acid + eicosapentaenoic acid (DHA+EPA) in the muscle significantly increased (P < 0.05), while the contents of moisture and monounsaturated fatty acids (∑MUFAs) significantly decreased (P < 0.05). The activities of acetyl CoA carboxylase a (ACCα), glucose-6-phosphate dehydrogenase (G6PD), and stearoyl-CoA desaturase (SCD) in the liver significantly increased (P < 0.05). The expression levels of catalase (cat), alkaline phosphatase (alp), nuclear factor erythroid 2-related factor 2 (nrf2), lysozyme (lyz), glutathione S-transferase (gst), glutathione peroxidase (gsh-px), and superoxide dismutase (sod) genes in the liver significantly increased (P < 0.05). The expression levels of tumor necrosis factor α (tnf-α), interferon-γ (inf-γ), interleukin 6 (il-6), interleukin 8 (il-8), interleukin 1β (il-1β), and transforming growth factor-β (tgf-β1) genes in the liver, spleens, and head kidney significantly increased (P < 0.05), while the expression level of interleukin 10 (il-10) gene significantly decreased (P < 0.05). In conclusion, the addition of different levels of marine red yeast could significantly affect the serum biochemistry, muscle composition, muscle fatty acid composition, lipid metabolism enzyme activity, and expression of antioxidant and inflammatory genes in juvenile GIFT tilapia. Based on the results, the optimal dietary marine red yeast level was 0.50 %. [ABSTRACT FROM AUTHOR]

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies. [ABSTRACT FROM AUTHOR]

In order to evaluate of injection of different levels of vitamin E-selenium supplementation in late pregnancy of cows and its effects on growth performance and immunity of their male calves, 28 Holstein dairy cows 28 days before calving in a complete design were randomly selected with 7 replications and 4 treatments. Experimental treatments included injection of 0, 15, 30 and 45 mL of E-selenium supplementation before calving. Injections of selenium (sodium selenite) and vitamin E (DL alpha tocopherol acetate) supplements were given at 28 and 14 days before delivery. Blood samples were taken from calves at the end of the experimental period (45 days after birth) to measure blood parameters. The results showed that injection of vitamin E-selenium solution in pregnant cows did not affect birth weight, feed intake and feed conversion ratio and dry matter digestibility of calves, while the final weight of calves increased (P<0.05). Blood parameters of glucose, albumin, cholesterol, globulin and urea were not significantly affected, but injection of vitamin E-selenium in pregnant cows increased blood triglyceride concentration compared to the control group (P<0.05). The results showed that the glutathione peroxidase concentration in calves was significantly increased by injecting vitamin E and selenium solution in pregnant cows (P<0.05). Also, triiodotronine and tetraidotronin hormones concentration was significantly increased by injecting 15 mL of vitamin and selenium solution in pregnant cows compared to the control group. However, betahydroxybutyrate, malondialdehyde and non-esterified fatty acids concentrations were not affected by solution injection. The results showed that skeletal growth of calves was not affected by injection of vitamin E-selenium solution in dry cows. In general, it is concluded that injection of vitamin E-selenium in pregnant cows could improve the final weight, glutathione peroxidase concentration, the hormones triiodotronine and tetraiodotronine in calves. [ABSTRACT FROM AUTHOR]

The production of charcoal is associated with atmospheric pollution and several processes involving oxidative stress in the population. Therefore, the main objective of this project was to evaluate the effects caused by particulate matter on oxidative stress parameters in workers working in charcoal production in Barão do Triunfo. Atmospheric particles were collected using a particle sampler and biological material collected from workers for analysis of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant power (FRAP). The control group was selected from an existing database, from a clinical analysis laboratory in the city, consisting of healthy individuals not exposed to particulate matter. The results for particulate matter concentrations averaged 16.46 µg/m3 for fine particulate matter and 300.12 µg/m3 for coarse particulate matter. The results of the socio-demographic analyzes of the control group show a prevalence of females who have completed secondary education, with an average monthly income of up to two minimum wages. In the exposed group, there is a prevalence of male individuals, with complete primary and secondary education, monthly income above two minimum wages, the majority of workers without the habit of smoking. In the exposed group there was an increase in GPx and a decrease in SOD compared to the control group. There was no significant difference for FRAP between the control group and the exposed group. Thus, we can conclude that workers exposed to particulate matter have higher levels of oxidative enzymes and decreased oxidative defenses when compared to the control group. [ABSTRACT FROM AUTHOR]

Background: The study investigates the effects of four different doses of computed tomography (CT) x-ray radiation on the oxidation markers, endogenous antioxidant enzymes, and lipid profiles of male Wistar albino rats. Materials and methods: Thirty healthy male Wistar albino rats weighing 180-200g were assigned into five groups of 6 rats each. Rats in groups A, B, C, and D underwent non-contrast helical total body irradiation and received varying doses of CT radiation, while group E received sham irradiation and served as a control. Glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) activities, serum levels of malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were investigated using standard methods. Results: At 72 hours' post-irradiation, the mean serum activities of GPx, SOD, and CAT in the irradiated groups decreased significantly, while the serum levels of MDA, GSSG, TC, and LDL increased significantly compared to the control. Conclusion: The four different doses of CT radiation in the current study caused a significant decline in the endogenous antioxidant enzymes (GPx, SOD, and CAT) and, in contrast, induced a significant serum elevation of MDA and GSSG in the irradiated rats. The LDC and TC mean serum levels were also significantly elevated in the irradiated groups. [ABSTRACT FROM AUTHOR]

Background: Cyclophosphamide is a chemotherapeutic and immunosuppressive drug, however, its usage is constrained by the development of dose-dependent side effects, like hepatotoxicity and hemorrhagic cystitis. The proposed mechanism of these side effects is oxidative stress. This study focuses on the role of sea buckthorn seed oil, which is high in antioxidants, in reducing oxidative stress caused by cyclophosphamide. Objective: To ascertain how sea buckthorn berry seed oil affects the serum levels of antioxidant enzymes and lipid peroxidation marker in BALB/c mice under oxidative stress brought on by cyclophosphamide. Study type, settings & duration: This quasi-experimental study was carried out at the Department of Physiology, Foundation University School of Health Sciences, Islamabad from February to April 2018. Methodology: It was a quasi-experimental animal study. Thirty healthy male BALB/c mice were divided into three groups of 10 each. Group-1 served as negative control, group-2 was positive control and received cyclophosphamide (25 mg/kg body weight) intraperitoneally for 10 consecutive days. Group-3 was coadministered cyclophosphamide (same dose and route) with sea buckthorn berry seed oil (40 mg/kg body weight) orally for ten days. All animals were sacrificed on the 11th day. Serum levels of antioxidant enzymes and malondialdehyde as stress biomarkers were assayed in all three groups. Results: Malondialdehyde levels rose while antioxidant enzyme levels, including glutathione peroxidase, superoxide dismutase, and catalase, fell in group-2 receiving cyclophosphamide (p <0.05). The deviation from the control group values was partially mitigated by the co-administration of sea buckthorn berry seed oil in group-3. Conclusion: In the cyclophosphamide-induced oxidative stress, co-administration of sea buckthorn berry seed oil reduced both the reduction in antioxidant enzymes and the rise in the lipid peroxidation marker malondialdehyde. [ABSTRACT FROM AUTHOR]

Drought stress ranks among the most critical environmental challenges facing agriculture today, causing significant impairments to plant growth and development. In Morocco, these negative impacts are projected to intensify further under the combined pressures of climate change and the worsening water shortage crisis. The imperative need for sustainable arganiculture (cultivation of Argane trees) in dry lands necessitates the expeditious identification of drought-tolerant elite Argania spinosa trees. In this context, we investigated the drought tolerance of 2-year-old A. spinosa seedlings from two contrasting provenances Lakhssas (LKS) and Aoulouz (ALZ) under severe stress by evaluating their antioxidative defense mechanisms. A total of 24 parameters related to reactive oxygen species (ROS), oxidative damage, and enzymatic and non-enzymatic antioxidant defense were measured and compared between both provenances. The results showed that the drought-stressed conditions significantly increased the activity of enzymatic antioxidants, including superoxide dismutase, catalase, peroxidase, polyphenoloxidase, glutathione peroxidase, glutathione S-transferase, and ascorbate-glutathione cycle enzymes, as well as the content of non-enzymatic antioxidants, including reduced glutathione (GSH), ascorbic acid (AsA), a-Tocopherols (a-toc), polyphenols, anthocyanins, and group thiols. The ability of A. spinosa trees to greatly enhance their antioxidant system to limit cellular damage caused by ROS production might be an important attribute linked to drought tolerance. Regarding the inter-provenance variation under drought stress conditions, LKS provenance exhibited superior antioxidative capacity through enhanced AsA-GSH cycle activity and elevated levels of AsA-GSH, a-toc, and polyphenols. However, ALZ demonstrated elevated anthocyanin levels and reduced peroxidative stress markers (hydrogen peroxide and malonyldialdehyde). Significant and positive correlations were recorded between studied ROS and antioxidants. Investigating the multifaceted antioxidative defense system underpinning drought tolerance in A. spinosa can facilitate the identification of drought-tolerant argan trees for the development of a future breeding program allowing sustainable arganiculture in dry lands. [ABSTRACT FROM AUTHOR]

Purpose: Excessive fluoride ingestion induces dental fluorosis that is generated by oxidative stress-mediated apoptosis. Oppositely, regular exercise has been shown to ameliorate oxidative damages and alleviate cell apoptosis in various diseases. However, little attention is paid to the effect of exercise on dental fluorosis. Thus, we employed the exercise regime including forced treadmill running (FTR) in fluorosis mice to explore the effect. Methods: Briefly, three-week-old Institute of Cancer Research (ICR) mice drinking water contained 100 mg/L sodium fluoride (NaF) and 0 mg/L NaF were compulsively submitted to treadmill running for 12 months. Results: Results showed that 12 months of fluoride exposure markedly elevated the incisors fluorine concentrations. FTR restrained the elevation of cross-linked C-terminal telopetide of type I collagen (CTX-I) concentration in urine from mice after 12 months of fluoride exposure. The slightly reduced contents of reactive oxygen species (ROS), malondialdehyde (MDA) and observably enhanced activities of catalase (CAT), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) were found in the incisors of fluoride-toxic mice subjected to FTR. Furthermore, FTR restrained fluoride-caused ameloblasts apoptosis induced by MDA in incisors through reducing the mRNA expressions of p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK), IkappaB kinase-beta (IKK-β), Caspase3 and enhancing the mRNA expression of B-cell lymphoma 2 (Bcl-2), superoxide dismutase 1 (SOD1). Conclusions: Above results suggested that regular exercise may be a convenient therapy for dental fluorosis. [ABSTRACT FROM AUTHOR]

Background: Hippeastrum reticulatum (HR) belongs to the Amaryllidaceae, a well-known ornamental family. Objectives: This study was designed to reveal in vivo anti-acetylcholinesterase (AChE) and antioxidant activities and evaluate the acute toxicity of the alkaloid fraction (AF). Methods: The D-galactose-induced aging model and the scopolamine-induced cognitive-deficit model were used for the in vivo tests. The median lethal dose (LD50) of the AF was determined using the Litchfield and Wilcoxon method. Results: On the aging model, the AF at 10 and 15 mg/kg significantly improved the antioxidant markers including superoxide dismutase, glutathione peroxidase, and malonyl dialdehyde. Upon the scopolamine-injected mice, the AF at 10 and 15 mg/kg notably downregulated cerebral AChE in mice. The LD50 of the HR AF is 90.2 mg/kg. Conclusion: These findings provide strong evidence for the safety and advantages of utilizing HR in treating Alzheimer's disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the effect of intratympanic treatment with brain-derived neurotrophic factor embedded in collagen sponge and simultaneous oral administration of N-acetylcysteine (NAC) with amikacin on oxidative stress through glutathione peroxidase expression, audiological and histological changes in the cochlea of guinea pigs with ototoxicity caused by amikacin. MATERIALS AND METHODS: Fifty-five guinea pigs were included, in 50 ototoxicity occurred due to amikacin, they were divided into 5 groups of 10 animals each and were treated as follows: group I: without treatment, group II: post-hearing NAC, group III: simultaneous NAC-amikacin, group IV: saline solution and group V: brainderived neurotrophic factor. The animals were evaluated for 4 weeks with otoacoustic emissions by distortion products. Cochlear integrity was evaluated histologically and glutathione peroxidase production was evaluated immunohistochemically. Study was done from January 1st, 2022 to January 31, 2023. RESULTS: None of the animal reverted hearing loss. Histologically, groups I, II, III and IV showed severe loss of hair cells and mild in group V. In group I glutathione peroxidase production was severe; moderate in II, III and IV, and mild in V. CONCLUSIONS: Simultaneous and post-hearing loss treatment for NAC and intratympanic application of brain-derived neurotrophic factor do not prevent glutathione peroxidase production in guinea pigs with ototoxicity caused by amikacin, but they decrease it. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is one of the common psychiatric disorders that is characterized by abnormal neurobiological responses. Proprotein convertase subtilisin/ kexin 9 (PCSK9) is important in cholesterol homeostasis. Methods: This study aimed to investigate PCSK9 levels and oxidative stress with MDD disease. The study included 30 patients with MDD and 30 healthy controls. Their blood samples were collected in sterile tubes, and the serum PCSK9 concentration, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were determined by ELISA kits. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and copper concentration were determined manually. There was a significant increase in PCSK9 levels in the patient group (P<0.05). Results: The receiver operating characteristic (ROC) curve with a sensitivity of 57% and specificity of 52% was 0.928 (95% CI, 0.86-0.996) for PCSK9 in the patient group (P<0.001). It was found that MDA (P=0.036) level was higher in the MDD group, but TAC (P=0.445) level, SOD (P=0.148), GPx (P=0.019) activities, and copper concentration were lower in the patient group compared with the control group. Conclusion: The study results confirm the relationship between oxidative stress and MDD and also suggest a link between PCSK9 and MDD disease. [ABSTRACT FROM AUTHOR]

Background: Dementia is a complex condition that affects the elderly and expands global health burdens. Numerous endogenous and external activities can result in the production of reactive oxygen and nitrogen species (RONS). Goal: To evaluate the association between oxidative stress markers and dementia in elderly men. Patients and Methods: A case-control study. Eighty males who were admitted to the Geriatrics and Gerontology Departments at Ain Shams University Hospitals as well as those who were recruited from the geriatric medicine outpatients' clinic were included in the study. The participants were split into two groups: a case group, which consisted of 40 adults with dementia, and a control group, which consisted of 40 participants without dementia. Participants underwent geriatric evaluations, and blood samples were obtained for measurement of oxidative stress blood levels as malondialdehyde (MDA), glutathione peroxidase enzyme (GPX), and total antioxidant capacity (TAC) Results: MDA blood levels were significantly higher in the case group, while GPX and TAC blood levels were significantly lower in the case group. According to statistical analysis, GPX with a cutoff point of 83.2 or lower, TAC with a cutoff point of 20.9 or lower, and MDA with a cutoff point of >82.5; all had high specificity and sensitivity for detecting dementia cases. Conclusion: Higher blood levels of MDA and lower blood levels of GPX and TAC in dementia cases compared to the control group indicate that oxidative stress plays a substantial role in the development of dementia. [ABSTRACT FROM AUTHOR]

In a 56-day experiment, the effects of selenium-enriched yeast (SeY) on the growth, enzymatic activity of the gastrointestinal tract, oxidative stress parameters, and selected immunological parameters of sterlet, Acipenser ruthenus (L.), were analyzed. The concentration of selenomethionine (SeMet) from SeY in the feed was 0 mg kg−1 (C), 0.7 mg kg−1 feed (S1), 1.4 mg kg−1 feed (S2), and 2.1 mg kg−1 feed (S3). Statistically significant differences were found in the final fish body weight between the control and groups S1 and S3. A significant increase in lipase activity was found in the initial section of the small intestine of fish from group S3. The highest activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase was recorded in the liver of fish from group S2. Analyses of non-specific humoral response parameters showed an increase in ceruloplasmin activity in group S1. The lowest active dose of SeMet derived from yeast tested in this study that stimulated humoral immunity and fish growth was 0.7 mg kg−1 feed (S1). [ABSTRACT FROM AUTHOR]

Objectives: Alzheimer's disease is primarily caused by neurotoxic effects of amyloid beta Aβ(25-35) peptide accumulation and increased levels of Acetylcholinesterase Enzyme (AChE). Acetylcholinesterase inhibitors report for the effective management of cognitive and motor disorders. In the current study the impact of Diplocyclos palmatus Methanolic (DPM) seed extract and its Chloroform (DPC) fractions were investigated in mice with Amyloid beta (Aβ)-induced experimental Alzheimer's disease. Materials and Methods: Acute toxicity study was performed based on the guidelines of OECD 423 and doses were selected. Mice were administered with standard Donepezil (5 mg/kg/oral) and two doses each of DPM and DPC daily for 21 days (200 mg/kg and 400 mg/kg/oral). Aβ was given by Intra Cerebro Ventricular (ICV) injection in a single dose 3 mg/kg. Cognitive abilities were assessed using the conditioned avoidance test, the rectangular maze and Y-maze. On 22nd day mice were sacrificed, then isolated brain homogenate used for estimation of biochemical parameters such as reduced Glutathione peroxidase (reduced GSH), Malondialdehyde (MDA), nitrite level and AChE levels. Results: Administration of DPM and DPC extracts effectively reduces behavioral and biochemical abnormalities in dose dependent way. Conclusion: Diplocyclos palmatus seeds showed neuroprotective effect on Aβ-induced AD in mice due to their antioxidant and AChE activity. [ABSTRACT FROM AUTHOR]

Epilepsy is the chronic non-communicable disease of the nervous system most prevalent in the world. Valproic acid (VPA) is one of the most used drugs in the treatment of epilepsy but with various side effects. One of the organs that can be affected is the testis, where it has been seen that men treated with VPA reduce their fertility rates, in addition to causing endocrine disorders by decreasing androgens and gonadotropins. In animal models, it has been shown to reduce the weights of the glands attached to the male reproductive tract, as well as at the testicular level, decreasing sperm concentration and increasing apoptotic cell count. These effects are because VPA increases reactive oxygen species (ROS), causing damage to macromolecules and affecting all cellular processes sensitive to oxide reduction. Throughout testicular development, in utero, it has been seen that the expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase, are lower during early embryonic development, as well as vitamin E (VE) is decreased. Therefore, they are not sufficient to reverse the toxic effects of ROS. The objective of this study was to review the use of VPA during pregnancy, its effect on testicular development, and to explore the potential protective role of vitamin E. [ABSTRACT FROM AUTHOR]

Introduction. Antibody mediated rejection (AMR) is a major challenge in kidney transplantation and adversely affects allograft survival. Oxidative stress (OS) is implicated in AMR pathogenesis by triggering inflammation, apoptosis and fibrosis in the graft tissue. However, the status of OS and antioxidant defense in AMR patients remains unclear. We aimed to evaluate the levels of OS markers and antioxidant enzymes in AMR patients. Methods. We conducted a case-control study involving 22 biopsyproven AMR patients (test group) and 14 kidney recipients with stable graft function (control group). Serum total oxidant status (TOS), total antioxidant capacity (TAC), total thiol groups, nitric oxide (NO), 8-isoprostane (8-IP) were determined and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured by spectrophotometric methods. Results. Data analysis showed significant increases in TOS, TAC and 8-IP levels together with marked reductions in NO and total thiol groups in AMR patients. CAT and GPx activities did not differ between groups, however SOD activity was significantly lower in AMR patients. Conclusion. Our study showed increased OS and impaired antioxidant defense in AMR patients. NO level may serve as a potential biomarker of OS severity and immune response in AMR. Further studies are required to elucidate the mechanisms and consequences of OS in AMR and to explore the therapeutic potential of antioxidants. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the effects of high moisture ear corn (HMEC) on production performance, milk fatty acid composition, serum antioxidant status, and immunity in primiparous dairy cows. Methods: A total of 45 healthy primiparous Holstein cows (36.50±4.30 kg of milk/d, 201±9.00 lactating days in milk) were sorted into 3 groups: control group (CG, n = 15); 50% HMEC (replacing 50% steam-flaked corn with HMEC, n = 15); and 100% HMEC (replacing steam-flaked corn with HMEC, n = 15) on an equal dry matter (DM) basis. The study consisted of adaptation period of 14 days, followed by a formal period of 60 days. Feed intake and milk yield were recorded daily. Milk and blood samples were collected on 1, 30, and 60 d of the experimental period. Results: The 50% HMEC group and 100% HMEC group significantly increased (p<0.05) milk yield and DM intake in dairy cows compared to the control group (CG). The 100% HMEC group showed an increase (p<0.05) in 4% fat-corrected milk (4% FCM). Both the 50% HMEC group and 100% HMEC group exhibited significant decreases (p<0.05) in the content of C10:0, C12:0, and C14:0 fatty acids, along with a significant increase (p<0.05) in cis-9C18:1 content. The saturated fatty acid content was significantly lower (p<0.05) in the 50% HMEC and 100% HMEC groups than that of CG. Conversely, the monounsaturated fatty acid content was higher (p<0.05) in the 50% HMEC and 100% HMEC groups than that in CG. Notably, the 100% HMEC group significantly increased (p<0.05) the serum superoxide dismutase and glutathione peroxidase content, while also decreasing the serum malondialdehyde content (p<0.05). Moreover, the 100% HMEC group significantly increased (p<0.05) the content of immunoglobulin G (IgG) and IgM. Conclusion: High moisture ear corn could improve production performance and milk fatty acid levels and enhance immunity and antioxidant capacity in dairy cows. These results lay the foundation for the wider application of HMEC in ruminant animal diets. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the effects of yacon (Smallanthus sonchifolius) juice byproduct (YJB) on the growth performance, digestive and antioxidant enzyme activities, and disease resistance against Streptococcus iniae of juvenile black rockfish (Sebastes schlegelii) based on different feeding schedules. Four different YJB feeding strategies were evaluated: feeding the fish a basal diet continuously (control, T0), feeding them YJB (2.5 g/kg) continuously (T1), feeding them YJB for 1 day and the basal diet the next day (T2), and feeding them YJB for 1 day and the basal diet for the following 2 days (T3). No difference in survival among the treatments was found after the 8-week feeding trial (p > 0.05). However, the T1 and T2 groups exhibited significant enhancements in final body weight, weight gain, and specific growth rate compared with the T0 and T3 groups. Furthermore, the T1 and T2 groups showed a significant improvement in feed consumption, feed efficiency, and protein efficiency ratio compared with the T0 and T3 groups. No significant differences in the condition factor or viscerosomatic and hepatosomatic indices were observed among all the groups. Intestinal amylase, trypsin, and lipase activity was significantly (p < 0.05) higher in the T1 and T2 groups than in the T0 and T3 groups. Lysozyme, superoxide dismutase, and catalase activity along with glutathione peroxidase content were significantly (p < 0.05) higher under all YJB feeding regimens than those under the control treatment. The survival rates in all the YJB treatment groups after the S. iniae challenge were significantly (p < 0.05) enhanced. In conclusion, we recommend offering YJB at day-to-day intervals to improve growth performance, digestive enzyme activity, antioxidant status, and disease resistance against S. iniae. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to comprehensively assess the therapeutic potential of clove extract in mitigating testicular damage and preserving male reproductive function under hypoxic conditions in male rats. Materials and Methods: We randomly divided 24 male rats into three groups: a hypoxia group that just received normal saline, a hypoxia + clove extract (4 mg/kg) group, and a sham operation group without treatment. After eight weeks, the serum level of oxidative stress parameters was examined, and the testicle histopathological examination, such as seminiferous tubule diameters and epithelium thickness, was assessed. Results: The serum malondialdehyde (MDA) concentration was significantly enhanced in the hypoxic group, and the levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) declined (P < 0.05). The diameters and thickness of the seminiferous tubule were diminished notably (P < 0.05). Johnson's score decreased in the hypoxic group. Treatment with clove extract also led to improvements in this parameter. Conclusions: Our study provides compelling evidence for the therapeutic potential of clove extract in mitigating testicular injury associated with varicocele-induced testicular hypoxia in male rats. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored the liver-protective effects of dapagliflozin and silymarin, alone and combined, against liver damage caused by carbon tetrachloride (CCl4) in rats. Thirty rats were divided into five groups. All groups except the normal control group were given CCl4 to induce liver damage. The other groups received treatments with gum acacia, silymarin, dapagliflozin, or a combination of dapagliflozin and silymarin for 14 days. The results show that both dapagliflozin and silymarin, alone and combined, significantly reduced liver damage markers in the blood compared to the group that only received CCl4. Additionally, these treatments lowered levels of inflammatory substances and increased antioxidant enzyme levels in the liver. The combination of dapagliflozin and silymarin was especially effective, suggesting they work well together to protect the liver. This study highlights the potential of dapagliflozin and silymarin in preventing liver damage by influencing specific protective pathways in the body. This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways. [ABSTRACT FROM AUTHOR]

This research aims to explore the relationship between glutathione peroxidase (GPX) expression variations in papillary renal cell carcinoma (pRCC) and patient survival, while also developing and evaluating a customized survival prediction model based on GPX. The transcriptomic dataset, including clinical parameters and GPX expression levels, is sourced from The Cancer Genome Atlas (TCGA) database, comprising 290 individuals diagnosed with pRCC. We utilized a univariate Cox regression model to select differentially expressed genes. Subsequently, we calculated risk scores through the least absolute shrinkage and selection operator (LASSO) regression. Based on the median risk score, patients were categorized into high and low-risk groups, establishing a prognostic risk model. Following this, the relationship between the risk model and the survival of pRCC patients was revealed through Kaplan–Meier survival curve analysis. The sensitivity and specificity of the predictive model were evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, chemotherapy drug sensitivity analysis was conducted on patients in the high and low-risk groups. A risk-scoring model was built by selecting GPX7 and GPX8. Compared to the low-risk group, individuals in the high-risk category showed significantly reduced overall survival rates (p=0.018). Additionally, validation results demonstrated the model's good predictive accuracy. The risk-scoring model constructed based on GPX family genes provides an innovative biomarker for forecasting the prognosis of pRCC and serves as a reference for individualized therapy in pRCC. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression. [ABSTRACT FROM AUTHOR]

AIM: The study aimed to explore the effect of curcumin (Cur) on lipopolysaccharide (LPS)-induced RAW264. 7 cell-derived osteoclasts, together with its underlying mechanism. METHODS: An osteoclast model was established by treating RAW264. 7 cells with LPS. The viability of the cells was assessed by CCK-8 assays and osteoclast formation was evaluated by tartrate-resistant acid phosphatase (TRAP) activity. The levels of reactive oxygen species (ROS), Fe2+, glutathione (GSH), and malondialdehyde (MDA) were examined by biochemical assays. Mitochondrial morphology was assessed by transmission electron microscopy. The mRNA and protein levels of p53, glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were determined by RT-qPCR and Western blot, respectively. RESULTS: Treatment with LPS successfully induced osteoclasts formation in RAW264. 7 cells. The TRAP results showed that compared with the LPS-treated group, the number of osteoclasts and TRAP activity in the curcumin-treated group decreased dose-dependently (P<0. 01). Compared with the control group, the LPS+Erastin group showed significantly increased TRAP activity (P<0. 01), while after curcumin treatment, the TRAP activity declined in a dose-dependent manner (P<0. 01). The results of the biochemical tests showed that compared with the control group, the LPS+Erastin group had significantly elevated levels of ROS, Fe2+, and MDA, while the GSH level was significantly reduced (P< 0. 01, and compared with the LPS+Erastin group, the ROS, Fe2+, and MDA levels in the curcumin group decreased (P< 0. 01) and GSH levels increased (P<0. 01). These effects were all dose-dependent. Transmission electron microscopy showed that compared with the LPS group, the LPS+Erastin group had reduced mitochondrial cristae and increased membrane density, while after treatment with curcumin, both these effects were reversed. The RT-qPCR and Western blot results showed that compared with the control group, the mRNA and protein levels of p53 in the LPS+Erastin group were significantly increased, while those of of SLC7A11 and GPX4 were significantly reduced (P<0. 01). After curcumin treatment, the p53 mRNA and protein levels were reduced while the levels of SLC7A11 and GPX4 were increased (P<0. 01). CONCLUSION: Curcumin can inhibit lipopolysaccharide-induced differentiation of RAW264. 7 cells into osteoclasts, and its mechanism may be related to the inhibition of the p53/SLC7A1 1/GPX4 signaling pathway. [ABSTRACT FROM AUTHOR]

AIM: To investigate the protective effect of total flavonoids from Patrina villosa Juss (PJF) on the lung in an experimental rat model of acute lung injury (ALI), and to elucidate the potential mechanism. METHODS: The ALI rat model was established by instilling 5 mg/kg of lipopolysaccharide (LPS) into the airway. Sixty male SD rats were randomly divided into 4 groups: control, LPS, LPS+low-dose PJF (receiving 100 mg/kg PJF one hour before ALI modeling) and LPS+high-dose PJF (receiving 300 mg/kg PJF one hour before ALI modeling). Each group consisted of 15 animals. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected from all groups 24 h after modeling. For assessment of lung tissue morphology, HE staining was performed. The wet/dry weight ratio of the lung tissue was determined using the wet/dry weighing method. Evans blue staining was conducted to assess epithelial barrier permeability in lung tissues. ELISA was used to detect the levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in the BALF, as well as oxidative stress markers including superoxide dismutase (SOD), myeloperoxi-dase (MPO) and glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) content in the lung tissue. The expression levels of C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78) and X-box binding protein 1 (XBP1) in the lung tissue were analyzed by Western blotting. RESULTS: Compared with control group, the rats in LPS group exhibited a blurred alveolar structure with a significant infiltration of inflammatory cells. The ALI score and the wet/dry weight ratio of the lung tissue were increased (P<0. 05). Concurrently, the levels of IL-6, IL-1β and TNF-α in the BALF, along with MDA content and MPO activity in the lung tissue, were elevated (P<0. 05). Additionally, the protein levels of CHOP, GRP78 and XBP1 were up-regulated in the lung tissue (P<0. 05), while the SOD and GSH-Px activity was significantly decreased (P<0. 05). Compared with LPS group, PJF intervention exerted beneficial effects on the lung tissue morphology with reduced ALI score and lower lung wet/dry weight ratio (P<0. 05). Moreover, the levels of IL-6, IL-1β and TNF-α in BALF, as well as MDA content, MPO activity and the protein levels of CHOP, GRP78 and XBP1 in the lung tissue were all significantly decreased (P<0. 05), while the SOD and GSH-Px activity was significantly increased (P<0. 05). The efficacy in high-dose group exceeded that in low-dose group. CONCLUSION: The PJF have protective effect on the lungs of rats with ALI, and its mechanism may be related to the inhibition of inflammation, oxidative stress and endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]