18[Formula: see text]-Glycyrrhetinic Acid Inhibits TGF-[Formula: see text]-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3.

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

Type-2 11ß-hydroxysteroid dehydrogenase promotes the metastasis of colorectal cancer via the Fgfbp1-AKT pathway.

Type-2 11ß-hydroxysteroid dehydrogenase (HSD11B2) is a key enzyme which converts cortisol to inactive cortisone and is involved in tumor progression and metastasis. Several studies have shown that the promotion of tumor progression and metastasis by HSD11B2 resulted from its physiological function of inactivating glucocorticoids (GC). However, the underlying molecular mechanisms by which HSD11B2 drives metastasis, in addition to inactivating GC, are still unclear. In our study, a series of in vivo and in vitro assays were performed to determine the function of HSD11B2 and the possible mechanisms underlying its role in CRC metastasis. mRNA transcriptome array analysis was used to identify the possible downstream targets of HSD11B2. We found that the ectopic expression of HSD11B2 significantly promoted the migration, invasion and metastasis of colorectal cancer (CRC) cells both in vitro and in vivo, while it did not affect their proliferation in either case. Mechanically, HSD11B2 appeared to enhance cell migration and invasion by upregulating the expression of fibroblast growth factor binding protein 1 (Fgfbp1), and subsequently increasing the phosphorylation of AKT. Furthermore, AKT activation partially mediated the increased expression of Fgfbp1 induced by HSD11B2. HSD11B2 expression was positively correlated with Fgfbp1 and p-AKT expression in clinical samples of CRC. Additionally, knockdown of either Fgfbp1 or AKT impaired the migration and invasion capability of CRC cells with HSD11B2 overexpression, suggesting that HSD11B2 promoted the migration, invasion and metastasis of CRC cells via the Fgfbp1-AKT pathway. Therefore, targeting HSD11B2 or Fgfbp1 may be a novel treatment strategy for inhibiting the metastasis of CRC.

Development of fluorogenic probe-based and high-resolution melting-based polymerase chain reaction assays for the detection and differentiation of Bartonella quintana and Bartonella henselae.

Bartonella henselae and Bartonella quintana are the major etiological agents of infective endocarditis, which pose a serious threat to human health. To simultaneously detect and differentiate B. henselae and B. quintana, a reliable and fast method to simultaneously detect and differentiate B. henselae and B. quintana is required. In this study, we developed and validated two rapid, highly sensitive and specific, duplex, real-time polymerase chain reaction (PCR) assays-one based on high-resolution melting (HRM) analysis, and the other on TaqMan probes-to simultaneously detect and differentiate B. henselae and B. quintana. The sensitivity of developed assays were found 100 times more sensitive than that of conventional PCR. The specificity of the assays were validated by the absence of any cross reaction with the other Bartonella species, non-Bartonella bacteria and other animals. The results indicate that the duplex HRM-based and TaqMan probe-based assays have high specificity and sensitivity, and good reproducibility for simultaneous the detection of B. henselae and B. quintana. They are cost-effective, sensitive and reliable methods; and are thus suitable for clinical diagnosis, epidemiological surveys, and disease surveillance.

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt-Jakob disease.

Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt-Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations.