Chalcomoracin promotes apoptosis and endoplasmic reticulum stress in hepatocellular carcinoma cells.

Chalcomoracin (CMR), a Diels-Alder adduct obtained from mulberry leaves, demonstrated wide-spectrum anti-cancer activity. Herein, we aimed to explore the function of CMR and how it works in hepatocellular carcinoma (HCC). Human HCC cell lines Hep3B and SNU-387 were cultured and treated with various concentrations of CMR (1.5, 3, and 6 µM). Subsequently, the effects of CMR on cell viability, colony formation, apoptosis, migration, and invasion abilities were studied in vitro. Furthermore, the levels of endoplasmic reticulum (ER) stress-related proteins and mitogen-activated protein kinase (MAPK) pathway-related proteins in cells under CMR exposure were detected using western blot. Experiments in vivo were conducted to examine the effects of CMR on tumor growth in HCC. CMR administration inhibited the viability and clonogenic, migration, and invasion abilities, as well as promoted cell apoptosis and ER stress in Hep3B and SNU-387 cells. In addition, CMR treatment reduced the phosphorylation levels of ERK, P38, and JNK in the MAPK pathway. Moreover, an in vivo study showed that CMR administration could inhibit tumorigenesis and MAPK pathway activity in HCC. Our data indicate that CMR has the potential to inhibit the development of HCC, potentially through the inhibition of the MAPK pathway. These findings suggest that CMR may have promising applications as an anticancer agent in future therapeutics for HCC.

Birth Weight and Incidence of Breast Cancer: Dose-Response Meta-analysis of Prospective Studies.

BACKGROUND: Many studies have shown the association between birth weight and breast cancer (BC), but the evidence remains limited and inconsistent, especially in different menopause status. We sought to clarify the relationship and shape of the dose-response relation between birth weight and BC. METHODS: The Web of Science, PubMed, and Embase databases were searched for prospective studies involving the relationship between birth weight and risk of BC published to November 2019. Random effects of generalized least squares regression models were used to estimate the quantitative dose-response association, and restricted cubic splines were used to model the association. RESULTS: We included reports of 16 prospective studies describing 16,000 incident cases among 553,644 participants. We identified a modest-in-magnitude, but significant, association between birth weight and BC risk: risk increased by 2% (risk ratio, 1.02, 95% confidence interval, 1.01-1.03) and 9% (risk ratio, 1.09, 95% confidence interval, 1.04-1.15) with a per-500 g birth weight increment in all ages and premenopausal women, respectively. Our results showed a linear dose-response relationship between birth weight and BC risk (Pnonlinearity = .311) in premenopausal women, with statistical significance when birth weight was above about 3.5 kg. No significant association was found in postmenopausal women. CONCLUSION: Higher birth weight has a relationship with increased risk of BC in premenopausal women, particularly when birth weight is above 3.5 kg.

[Risk factors of cubitus varus in humeral condylar fracture after conservative treatment in child].

OBJECTIVE: To further investigate the risk factors of cubitus varus in humeral condylar fracture after conservative treatment in children through Logistic regression analysis, so as to guide the clinical treatment. METHODS: Children with humeral condylar fracture who were treated by manipulative reduction and plaster fixation in our hospital from March 2008 to December 2014 were studied. The clinical data including age, gender, BMI, time from injury to reduction, direction of displacement, rotation displacement, fixed position, and epiphyseal injury were collected. First, preliminary screen the risk factors through univariate analysis of the above data, then determine the risk factors of cubitus varus through multivariate Logistic regression analysis of the significant factors from univariate analysis. RESULTS: Univariate analysis showed that time from injury to reduction, direction of displacement, rotation displacement and epiphyseal injury were significantly correlated with the cubitus varus. Multivariate Logistic regression analysis showed that time from injury to reduction which was longer than 8 h [P=0.017, OR=3.303(1.243-8.774)], ulnar displacement [P=0.001, OR=11.951(2.895-49.335)], rotation displacement [P=0.003, OR=4.190(1.643-10.685)]and epiphyseal injury [P=0.000, OR=7.092(2.557-19.671)] were independent risk factors of cubitus varus. CONCLUSIONS: Time from injury to reduction, ulnar displacement, rotation displacement and epiphyseal injury are independent risk factors of cubitus varus. So it need corresponding treatment according to different risk factors.

Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors.

Our recent studies demonstrate that burn trauma induces leaky sarcoplasmic reticulum (SR) in heart due to excessively active ryanodine receptor (RyR) function. SR Ca(2+) leak causes partial depletion of SR Ca(2+) content and disturbances in intracellular Ca(2+) homeostasis, resulting in the pathogenesis of burn-generated cardiac dysfunction. This study investigated the role of polydatin, a resveratrol glucoside, in preventing SR leak and its therapeutic effect against burn-generated cardiac dysfunction. We found that polydatin treatment improved cardiac function impaired by burn injury of 30% of total body surface area. Parallel to the alterations in cardiac function, polydatin significantly increased the defective systolic Ca(2+) transient and contractility in burn-traumatized cardiomyocytes. Burn injury increased the occurrence of Ca(2+) sparks. The enhancement of Ca(2+) spark-mediated SR leak caused partial depletion of SR Ca(2+) content in burn-traumatized cardiomyocytes. Furthermore, we found that the content of free thiols (the number of reduced cysteines) in RyR2 in cardiomyocytes determined by the monobromobimane fluorescence of RyR2 was decreased markedly in burn-traumatized hearts. Polydatin treatment decreased intracellular reactive oxygen species levels and restored the amount of free thiols in RyR2 in burns. Concomitantly, polydatin corrected Ca(2+) spark-mediated SR leak and restored SR Ca(2+) load. The systolic Ca(2+) transient and cellular contractility were significantly increased by polydatin treatment. Taken together, the present findings provide the first evidence demonstrating that polydatin prevents enhanced Ca(2+) spark-mediated SR leak by reducing oxidative stress in RyR2 in burn-traumatized heart, leading to protection of cardiac function against burn injury.