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Dysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10−3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p =.72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea. [ABSTRACT FROM AUTHOR]

Background: Peptic ulcer disease has been a major threat to the world's population, which remains a significant cause of hospitalization worldwide and healthcare resource utilization. Objectives: We aimed to describe the global burden, trends, and inequalities of peptic ulcer disease. Design: An observational study was conducted. Methods: In this secondary analysis of the Global Burden of Disease, Injuries, and Risk Factors Study 2019, we extracted data for age-standardized incidence rates (ASIRs), disability-adjusted life year rates (ASDRs), and mortality rates (ASMRs); then, we stratified by age, level of regionals, and country; subsequently, we calculated estimated annual percentage changes (EAPC) of ASIR, ASDR, ASMR, and quantified cross-country inequalities in peptic ulcer disease mortality. Results: Globally, ASIR showed a continuous downward trend, from 63.84 in 1990 to 44.26 per 100,000 population in 2019, with an annual decrease of 1.42% [EAPC = −1.42 (95% CI: −1.55 to −1.29)]. ASDR showed a continuing downward trend, and the EAPC was −3.47% (−3.58 to −3.37). ASMR showed a persistent decline, declining by nearly half in 2019 compared to 1990 (3.0 versus 7.39 per 100,000 population), with an annual decrease of 2.55% [EAPC = −3.36 (95% CI: −3.47 to −3.25)]. A significant reduction in sociodemographic index (SDI)-related inequality, from an excess of 190.43 disability-adjusted life years (DALY) per 100,000 (95% CI: −190.83 to −190.02) between the poorest and richest countries in 1990 to 62.85 DALY per 100,000 (95% CI −62.81 to −62.35) in 2019. Conclusion: Global peptic ulcer disease morbidity and mortality rates decreased significantly from 1990 to 2019. These health gains were in accordance with a substantial reduction in the magnitude of SDI-related inequalities across countries, which is paired with overall socioeconomic and health improvements observed in the region. [ABSTRACT FROM AUTHOR]

This study evaluated the subacute toxicity and toxicokinetics of a potential anti-cancer drug candidate, pterostilbene, in rats. Animals were orally administered at two repeated doses of 200 and 500 mg/kg for 28 days. No mortality was observed during the 28 days of continuous administration of pterostilbene. Body weight and food consumption in each group increased steadily, while no significant difference was found. Liver weight in the 500 mg/kg female, but not male group increased with mild cytoplasmic vacuoles observed in histopathological study. Toxicokinetics was assessed by measuring plasma concentrations of pterostilbene on the first and 28th day of administration using UPLC–MS/MS. Toxicokinetic parameters showed that AUC0–t significantly increased in all animals, while the increase in females was greater than males. System exposure of pterostilbene appeared to be linear within the administrated dose range. In conclusion, our findings suggested a minimal subacute toxicity profile of pterostilbene, which could strongly support further development of this compound as a novel anti-cancer agent. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the effect of aerobic exercise on improving damage to intestinal mucosal barrier function caused by obstructive jaundice (OJ) and explore the mechanism. Fifty male KM mice were divided into five groups: sham operation group (S), model group (M), exercise group (TM), DL-propargylglycine + exercise (PT) group, and sodium hydrosulfide + exercise (NT) group. Additionally, mice in S group underwent common bile duct ligation for 48 h to establish a murine obstructive jaundice model. In PT group, propargylglycine (40 mg/kg) was intraperitoneally injected 7 days after surgery. NaHS (50 μmol/kg) was intraperitoneally injected into mice in the NT group 7 days after surgery. The TM group, NT group and PT group exercised on a slope of 0% at a speed of 10 m/min without weight training (30 min/day). HE staining showed that the intestinal mucosa of group M was atrophied and that the villi were broken. The intestinal mucosal structure of mice in the TM group was improved. Serum assays showed that H2S levels were higher in the TM group than in the M group; compared with the levels in the TM group, the PT group levels were decreased and the NT group levels were increased. In addition, aerobic exercise inhibits the HMGB1/TLR4/NF-κB signaling pathway by promoting endogenous H2S production, thereby exerting a protective effect on the intestinal mucosal barrier. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite the worldwide prevalence of dermatophyte infections, only a few genes are reported to be related to dermatophyte infections. In addition, the mechanism by which different ecological dermatophytes infection leads to varying intensity of inflammation remains unclear. Objectives: To investigate the mechanism of varying intensity of skin inflammation caused by different ecological dermatophytes infection. Methods: We infected HaCaT cells with anthropophilic and geophilic dermatophytes to mimic various ecological dermatophyte infections. RNA‐sequencing (RNA‐seq) was employed to identify the change in the gene expression of HaCaT cells. To verify the expression of differentially expressed genes (DEGs), we selected 18 HaCaT cells genes to conduct qPCR experiments. In addition, immunoblotting was conducted to validate key genes from the MAPK signalling pathway. Results: After HaCaT cells were infected with the anthropophilic Trichophyton rubrum (T rubrum) and the geophilic Microsporum gypseum (M gypseum), 118 and 619 differentially expressed genes were identified in HaCaT cells, respectively. These genes may provide a clue as to how keratinocytes respond to anthropophilic and geophilic dermatophytes. We also found that JUN may play a critical role in keratinocytes infected with M gypseum. Conclusions: Differential gene expression in HaCaT cells may account for the various clinical presentation caused by anthropophilic and geophilic dermatophytes infections. In addition, the intense inflammatory reaction of M gypseum infection may be triggered by activating the JNK‐JUN signalling pathway. [ABSTRACT FROM AUTHOR]

Background: Extrahepatic metastatic hepatocellular carcinoma (HCC) and its insensitivity to chemotherapy are the main causes of poor prognosis in patients with HCC. This study investigated the anti-cancer effect of Macrothele raveni venom on intrarenal metastatic HCC.Materials and Methods: Subrenal capsule xenograft model of HCC was established by inoculation of H22 liver cancer cells.Results: The general health, histology, and molecular changes were observed after administering 10 times of different dose of Macrothele raven venom injections. A volume of 0.8 μg/ml and 1.0 μg/ml of Macrothele raven venom significantly improved general health status in mice with subrenal capsule HCC tumors. Hematoxylin and eosin staining showed that Macrothele raven venom dose-dependently reduced invasion and metastasis of liver cancer cells in the kidney. Immunohistochemistry and real-time polymerase chain reaction showed that Macrothele raven venom injection dose-dependently decreased PI3K mRNA and protein, Akt protein, and mTOR mRNA expression, but increased Bad mRNA and protein expression in the kidney with H22 tumor cell invasion. 0.8 μg/ml is the most effective dose for the treatment of intrarenal metastatic HCC.Conclusions: Macrothele raven venom dose-dependently inhibits invasion and metastasis of intrarenal metastatic HCC through inhibition of PI3K-Akt-mTOR signaling and increase of Bad expression. [ABSTRACT FROM AUTHOR]