Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

Context: Oxidative stress has a critical role in the development of physical fatigue and activation of matrix metalloproteinases-9 (MMP-9). Naringin (Nar) is a bioflavonoid that has antioxidant activity and suppresses MMP-9 expression. Objective: The present study evaluates the anti-fatigue activity of Nar on physical fatigue and serum MMP-9 concentration in rats. Materials and methods: Fifty female Wistar rats were randomly divided into five groups (n = 10); a control group, vehicle group and three Nar treatment groups. The Nar treated groups received different doses of Nar (40, 80 and 160 mg/kg/day) for 30 days. On the 30^th day, rats were sacrificed immediately after exhaustive swimming test. Serum MMP-9 concentration and several biochemical parameters related to fatigue were measured. Results: Exhaustive swimming time in the Nar-80 group significantly increased 1.78-, 1.53-, 1.5- and 1.3-fold compared with the control, vehicle, Nar-40 and Nar-160 groups, respectively. In addition, exhaustive swimming time in the Nar-160 group significantly increased 1.36-fold compared with the control group. Nar-80 significantly decreased LDH activity by 60.45% and 57.47% compared with the vehicle and control groups, respectively. Furthermore, Nar-80 and Nar-160 increased blood glucose levels by 19.56% and 18.38% compared with the control group, respectively. Nar-80 and Nar-160 significantly decreased serum MMP-9 concentration by 61.57% and 83.39% compared with the control group, respectively. Conclusion: Based on our data, Nar has anti-fatigue effects which may be attributed to its property in modulating energy metabolism and reducing serum MMP-9 concentration. Thus, Nar may be a promising agent for the treatment of physical fatigue.

This study investigated the effects of different doses of vitamin E on oxidative stress, cognitive function, and gene expression in aged mice. A total of 32 male mice, aged 12 months, were divided into a control group and three treatment groups. These groups received varying daily doses of vitamin E for a period of 28 days. The results showed significant improvements in cognitive function, specifically in working memory and spatial learning, in the groups that received vitamin E (100, 200, or 400 mg/kg) compared to the control group. The markers of oxidative stress and antioxidant enzyme activities also demonstrated improvements, with higher doses of vitamin E showing greater effects. The analysis of gene expression revealed increased expression of SIRT1, Nrf2, and Calstabin2, particularly at higher doses of vitamin E. These findings suggest that vitamin E supplementation may help counteract age‐related cellular changes. The study concludes that vitamin E supplementation can reduce oxidative stress, enhance cognitive function, and affect genetic markers of aging in mice, which may have therapeutic benefits in addressing age‐related cognitive decline and oxidative damage. Further research is necessary to investigate the clinical implications of these findings in humans.

In the current study, the effects of troxerutin (TRX) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats was investigated. Forty male Wistar rats were randomly divided into 4 groups and designated as control and TRX treatment at 75 (TRX75), 150 (TRX150), and 300 mg/kg per day (TRX300). The treated groups and control group received TRX and water orally for 7 days. After an exhaustive swimming test on the 7th day, all animals were euthanized immediately and several biochemical parameters related to fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue were measured. Our results showed that the exhaustion swimming time in the TRX300 groups significantly increased 1.2-fold compared with the control group (P < 0.001). TRX300 significantly reduced ALT (P < 0.05) activity and increased liver SOD activity compared with the control group (P < 0.01). Additionally, TRX significantly reduced the liver mRNA expressions of Bax (P < 0.001) and increased the Bcl-2/Bax ratio (P < 0.001) compared with the control group. Based on our data, TRX possesses anti-apoptotic and hepatoprotective action following exhaustive swimming exercise.

Previous studies have shown that several microRNAs (miRNAs) are dysregulated in the whole blood as well as diverse cells and tissues from rheumatoid arthritis (RA) patients. The aim of the current study was to determine if the expression of miR-146a, miR-103a, and miR-155 in whole blood of RA patients could confer potential markers in evaluating of activity-severity of the disease in RA patients with established disease. Whole blood samples were obtained from 30 RA patients and 30 healthy subjects. The RNA content of blood samples was isolated, cDNA was synthesized, and transcript levels of miR-146a, miR-103a, and miR-155 were determined using Real-time PCR. The clinicopathological characteristics of the patients were also evaluated. It was detected that expression level of miR-146a (fold change=1.85, P=0.004), miR-103a (fold change=2.44, P=0.0018), and miR-155 (fold change=1.94, P=0.0025) were significantly upregulated in the whole blood samples of RA patients in comparison to that of healthy subjects. Expression level of miRNAs was correlated with clinicopathological characteristics of the patients, including Disease Activity Score 28 (DAS28), Simple Disease Activity Index (SDAI), 28Tender Joint Count (TJC-28), 28Swollen Joint Count (SJC-28), C-reactive protein (CRP), Rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Upregulated levels of miR-146a, miR-103a, and miR-155 in the whole blood samples of RA patients could confer a potential marker of activity-severity of the disease in RA patients with established disease.