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Objective: Bone metabolism can be influenced by a range of factors. We selected children with self‐limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti‐seizure medications (ASMs) on bone metabolism. Methods: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross‐linked C‐telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3). Results: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3, other bone metabolism of the three groups were different (p <.001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p <.05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p <.05, Cliff's delta.282–.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p =.012, Cliff's delta =.316). Significance: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy. [ABSTRACT FROM AUTHOR]

As one of the triterpene extracts of Taraxacum, a traditional Chinese plant, taraxerol (TRX) exhibits antitumor activity. In this study, we evaluated the effects of TRX on the migration and invasion of MDA-MB-231 cells, analyzed the molecular mechanism through network pharmacology and molecular docking, and finally verified it by in vitro experiments. The results showed that TRX could inhibit the migration and invasion of MDA-MB-231 cells in a time- and concentration-dependent manner, while MAPK3 was the most promising target and could stably combine with TRX. In addition, the relative protein expression levels were detected by Western blot, and we observed that TRX could inhibit the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. Moreover, an ERK activator (tert-butylhydroquinone, tBHQ) partially reversed the suppressive effect of TRX on MDA-MB-231 cells. In conclusion, TRX inhibited the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. [ABSTRACT FROM AUTHOR]

Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta‐analysis and meta‐regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta‐analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta‐regression analysis was performed to estimate the association between the study‐specific hazard ratios and specific demographic variables. A meta‐analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First‐line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44–0.52) and second‐line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39–0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67–0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63–0.75) showed the greatest benefits when used as first‐line and second‐line chemotherapies, respectively. Subgroup meta‐analysis results revealed that dual‐regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III–IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Improvement in the quality of life is reflected in the narrowing of the gap between health-adjusted life expectancy (HALE) and life expectancy (LE). The effect of megacity expansion on narrowing the gap is rarely reported. This study aimed to disclose this potential relationship. Annual life tables were constructed from identified death records and population counts from multiple administrative sources in Guangzhou, China, from 2010 to 2020. Joinpoint regression was used to evaluate the temporal trend. Generalized principal component analysis and multilevel models were applied to examine the county-level association between the gap and social determinants. Although LE and HALE in megacities are increasing steadily, their gap is widening. Socio-economic and health services are guaranteed to narrow this gap. Increasing personal wealth, a growing number of newborns and healthy immigrants, high urbanization, and healthy aging have helped in narrowing this gap. In megacities, parallel LE and HALE growth should be highly considered to narrow their gap. Multiple social determinants need to be integrated as a whole to formulate public health plans. [ABSTRACT FROM AUTHOR]

Two new 2,5-diketopiperazines derivatives (1-2), together with eight known analogs (3-10), were isolated from a culture broth of an endophytic fungus Nigrospora camelliae-sinensis S30, derived from mangrove Lumnitzera littorea. Their complete structures were determined by a detailed analysis of spectroscopic data and ECD calculations. The antimicrobial activity and neuroprotective activity of these isolated compounds were also evaluated. [ABSTRACT FROM AUTHOR]