RESUMEN
Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.
Asunto(s)
Apoptosis , Autofagia , Proliferación Celular , Neoplasias Ováricas , Triterpenos , Proteína p53 Supresora de Tumor , Proteínas Quinasas p38 Activadas por Mitógenos , Humanos , Apoptosis/efectos de los fármacos , Femenino , Autofagia/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Triterpenos/farmacología , Triterpenos/química , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Estructura Molecular , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/químicaRESUMEN
BACKGROUND AND AIMS: Cardiovascular disease (CVD) is associated with inflammation and abnormal lipid metabolism. However, a single inflammatory index or a single lipid index cannot accurately predict the prognosis of CVD independently because it is prone to be affected by various confounding factors. METHODS: This population-based cohort study included 6,554 participants from the China Health and Retirement Longitudinal Study (CHARLS) to investigate correlations. In the present study, the occurrence of CVD events such as stroke and heart disease was evaluated by considering self-reported diagnoses at the beginning of the study and during wave 4, and a restricted cubic spline model was used to investigate potential nonlinear relationships in addition to multivariate logistic regression models. Stratified analyses were performed to examine how sociodemographic characteristics may influence the results. RESULTS: Seven years of follow-up (2011-2018) revealed that 786 people (11.99%) developed CVD. According to the adjusted model, the high-sensitivity C-reactive protein (hs-CRP)-to-high-density lipoprotein cholesterol (HDL-C) ratio is a contributing factor to CVD risk (OR 1.31, 95% CI 1.05-1.64). In addition, a nonlinear relationship was observed between the hs-CRP/HDL-C ratio and the occurrence of new CVD, stroke, or cardiac issues (Poverall <0.05, Pnonlinear <0.05). Moreover, noteworthy associations between the hs-CRP/HDL-C ratio and age were detected in the stratified analysis (P = 0.048), indicating that younger participants had more negative effects of a high hs-CRP/HDL-C ratio. CONCLUSIONS: According to the present cohort study, a high hs-CRP/HDL-C ratio is a significant risk factor for CVD, new stroke, and heart problems. Early intervention in patients with increased hs-CRP/HDL-C ratios may further reduce the incidence of CVD, in addition to focusing on independent lipid markers or independent inflammatory markers.
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Enfermedades Cardiovasculares , Accidente Cerebrovascular , Anciano , Persona de Mediana Edad , Humanos , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Estudios Longitudinales , InflamaciónRESUMEN
Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.
Asunto(s)
Meningitis Bacterianas , Niño , Lactante , Humanos , Estudios Retrospectivos , Meningitis Bacterianas/diagnóstico , Meningitis Bacterianas/epidemiología , Meningitis Bacterianas/tratamiento farmacológico , Streptococcus pneumoniae , Streptococcus agalactiae , Escherichia coli , IncidenciaRESUMEN
Background: To assess the prevalence and risk factors of NAFLD in non-obese patients with schizophrenia in a public psychiatric hospital in China. Methods: A total of 1,305 adult inpatients with schizophrenia in 2019 were included in this retrospective study. Body mass index (BMI) ≥ 25 kg/m2 was considered obese, and BMI < 25 kg/m2 was considered non-obese. We obtained the data from electronic records of the Affiliated Brain Hospital of Guangzhou Medical University. Results: A total of 1,045 non-obese patients and 260 obese patients were included in this study. The prevalence of NAFLD in non-obese patients was 25.0%, and it was much lower that in the obese patients (25.0% vs 64.6%, p < 0.001). Among the non-obese patients, there were significant differences in age, BMI, alanine aminotransferase (ALT), metabolic indices, and the prevalence of diabetes and hypertension between patients with NAFLD and patients without NAFLD. According to the results of binary logistic regression analysis, age, BMI, ALT, triglyceride (TG) and diabetes were significantly related to NAFLD among non-obese patients with schizophrenia. In contrast, HDL-C was was negatively associated with NAFLD among non-obese patients. Conclusion: This study suggested that NAFLD was common in patients with schizophrenia, even in non-obese patients with schizophrenia. In non-obese patients with schizophrenia, age, BMI, ALT, TG and diabetes are significantly associated with NAFLD. Moreover, HDL-C level was an independent protective factor against NAFLD. Given the adverse outcomes of NAFLD, it is necessary to increase awareness of NAFLD in patients with schizophrenia, especially in non-obese patients with schizophrenia.
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Endometrial receptivity is critical for the successful establishment of pregnancy in ruminants. Interferon tau (IFNT) plays a key role in promoting embryo attachment by activating the Janus kinase/signal transducer and activator of transcription pathway, which induces the expression of a series of interferon-stimulated genes (ISGs). In our previous study, sequencing analysis of goat endometrial epithelial cells (gEECs) treated with 20 ng/mL IFNT revealed a differentially expressed long non-coding RNA located on the STAT3 antisense chain, which we designated STAT3-AS. The aim of this study was to investigate the role and mechanism of STAT3-AS in establishing endometrial receptivity in goats. The results showed that STAT3-AS was expressed in both the nucleus and cytoplasm of gEECs, and its expression increased significantly in the uterus on day 15 of pregnancy. STAT3-AS expression was upregulated in gEECs treated with IFNT alone or in combination with progesterone and estradiol. Knockdown of STAT3-AS using specific short interfering RNA significantly inhibited the expression of classical ISGs such as interferon-stimulated gene 15 and 2',5'-oligodenylate synthetase 2, as well as uterine endometrial receptivity-related genes including homeobox gene A11, integrin beta 3, and vascular endothelial growth factor. Moreover, gEEC proliferation and the STAT3 pathway were suppressed in the absence of STAT3-AS. However, pretreatment with the STAT3 activator RO8191 restored the effect of silencing STAT3-AS on endometrial receptivity. Overall, these results suggest that STAT3-AS is an important regulator of endometrial receptivity in goats and that it regulates endometrial receptivity through the STAT3 pathway.