Advances in Promoting the Efficacy of Chimeric Antigen Receptor T Cells in the Treatment of Hepatocellular Carcinoma

HCC, one of the most common and deadly cancers worldwide, develops from hepatocytes and accounts for more than 90% of primary liver cancers. The current widely used treatment modalities are far from meeting the needs of liver cancer patients. CAR-T cell therapy, which has recently emerged, has shown promising efficacy in lymphoma and hematologic cancers, but there are still many challenges to overcome in its application to the clinical treatment of HCC, including osmotic barriers, the inhibition of hepatocellular carcinoma microenvironment activity, the limited survival and killing ability of CAR-T cells, and inevitable side effects, among others. As a result, a number of studies have begun to address the suboptimal efficacy of CAR-T cells in HCC, and many of these schemes hold good promise. This review focuses on advances in the past five years aimed at promoting the efficacy of CAR-T cell therapy for treatment of HCC

Biosynthesis of Fungal Natural Products Involving Two Separate Pathway Crosstalk

Fungal natural products (NPs) usually possess complicated structures, exhibit satisfactory bioactivities, and are an outstanding source of drug leads, such as the cholesterol-lowering drug lovastatin and the immunosuppressive drug mycophenolic acid. The fungal NPs biosynthetic genes are always arranged within one single biosynthetic gene cluster (BGC). However, a rare but fascinating phenomenon that a crosstalk between two separate BGCs is indispensable to some fungal dimeric NPs biosynthesis has attracted increasing attention. The hybridization of two separate BGCs not only increases the structural complexity and chemical diversity of fungal NPs, but also expands the scope of bioactivities. More importantly, the underlying mechanism for this hybridization process is poorly understood and needs further exploration, especially the determination of BGCs for each building block construction and the identification of enzyme(s) catalyzing the two biosynthetic precursors coupling processes such as Diels–Alder cycloaddition and Michael addition. In this review, we summarized the fungal NPs produced by functional crosstalk of two discrete BGCs, and highlighted their biosynthetic processes, which might shed new light on genome mining for fungal NPs with unprecedented frameworks, and provide valuable insights into the investigation of mysterious biosynthetic mechanisms of fungal dimeric NPs which are constructed by collaboration of two separate BGCs

Flavonoids in Ageratum conyzoides L. Exert Potent Antitumor Effects on Human Cervical Adenocarcinoma HeLa Cells In Vitro and In Vivo

The Ageratum conyzoides L. (A. conyzoides) is commonly used as a traditional medicine, and its antitumor effects have also been studied. However, the functional roles of flavonoids in A. conyzoides in antitumor activities have not been clarified. The present study is aimed at investigating the biological effects of flavonoids in A. conyzoides on human cervical adenocarcinoma. Firstly, we detected that flavonoids in A. conyzoides significantly inhibited the proliferation, invasion, migration, and clonality of human cervical adenocarcinoma HeLa cells in vitro. Furthermore, we found that flavonoids in A. conyzoides induced significant S phase arrest and apoptosis and obviously decreased the intracellular reactive oxygen species (ROS) level in HeLa cells. Finally, we found that flavonoids in A. conyzoides significantly inhibited the HeLa xenograft tumor growth and epithelial-mesenchymal transition (EMT) in vivo. In conclusion, our results demonstrated the obvious antitumor effects of flavonoids in A. conyzoides on HeLa cells, suggesting that flavonoids in A. conyzoides could be provided as a novel therapeutic compound for human cervical adenocarcinoma

Association of cholecystectomy with metabolic syndrome in a Chinese population.

An association between cholecystectomy and metabolic syndrome has not been fully established. Here we analyzed the association between cholecystectomy and metabolic syndrome in a Chinese population of 5672 subjects who undergone annual health checkups at the First Affiliated Hospital, College of Medicine, Zhejiang University between January 2011 and December 2012. The prevalences of gallstones, cholecystectomy and metabolic syndrome were 6.0%, 3.6%, and 32.5%, respectively. The prevalence of metabolic syndrome was significantly higher in subjects with a history of cholecystectomy (63.5%) than in those with gallstones (47.0%) or in those without gallstone disease (30.3%; P<0.01 for both). Multivariate logistic regression analysis showed that cholecystectomy was significantly associated with increased risk of metabolic syndrome (OR = 1.872; 95% CI: 1.193-2.937). However, the association of gallstones with metabolic syndrome was not statistically significant (OR = 1.267; 95% CI: 0.901-1.782). Altogether, our results suggest that cholecystectomy significantly increases the risk of metabolic syndrome