No abstract

Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV-infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY(®) SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07-112.50), 14.88 (2.02-109.72), 7.92 (1.88-33.32) and 2.32 (1.22-4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9-2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.

Exosomes are nanosized vesicles, released by various cells, which have essential roles in intercellular communication locally and systemically through transporting their contents such as proteins and lipids as well as RNA. It was clear that the element of contents in exosomes reassembled with the emerging of cancers. Over the past decade, researchers paid more attention to the role of exosomes in breast cancer. The purpose of this review was to discuss the details of the biological characteristics of exosomes in breast cancer. The discussion would focus on the role of exosomes in breast cancer development, progression, metastasis and drug resistance, as well as related therapeutic and diagnostic strategies.

Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe3O4 nanoparticles coated with oleic acid molecules as a nano-carrier. N-isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression in vitro and in vivo. The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model.

Background: NAFLD is tightly associated with various diseases such as diabetes, cardiovascular disease, kidney disease, and cancer. Previous studies had investigated the association between NAFLD and various extrahepatic cancers, but the available data to date is not conclusive. The aim of this study was to investigate the association between NAFLD and various extrahepatic cancers comprehensively. Methods: Searches were conducted of various electronic databases (PubMed, EMBASE, Medline, and the Cochrane Library) to identify observational studies published between 1996 and January 2020 which investigated the association between NAFLD and extrahepatic cancers. The pooled OR/HR/IRR of the association between NAFLD and various extrahepatic cancers were analyzed. Results: A total of 26 studies were included to investigate the association between NAFLD and various extrahepatic cancers. As the results shown, the pooled OR values of the risk of colorectal cancer and adenomas in patients with NAFLD were 1.72 (95%CI: 1.40-2.11) and 1.37 (95%CI: 1.29-1.46), respectively. The pooled OR values of the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in patients with NAFLD were 2.46 (95%CI: 1.77-3.44) and 2.24 (95%CI: 1.58-3.17), respectively. The pooled OR value of the risk of breast cancer in patients with NAFLD was 1.69 (95%CI: 1.44-1.99). In addition, NAFLD was also tightly associatied with the risk of gastric cancer, pancreatic cancer, prostate cancer, and esophageal cancer. Conclusions: NAFLD could significantly increase the development risk of colorectal adenomas and cancer, intrahepatic and extrahepatic cholangiocarcinoma, breast, gastric, pancreatic, prostate, and esophageal cancer. NAFLD could be considered as one of the influencing factors during the clinical diagnosis and treatment for the extrahepatic cancers.

No abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) naturally infects humans, and over 95% of healthy persons have no symptoms. KSHV causes three types of malignancies in immunosuppressed patients: Kaposi's sarcoma, body cavity-based lymphoma, and multicentric Castleman's disease (1-3). KSHV establishes a latent infection in most infected cells, whereas a small proportion of cells develop lytic infection. The genetic profiles of KSHV-infected populations differ from those of uninfected populations, with host cell transcriptional remodeling observed in latently KSHV-infected cells (4) and global mRNA shutoff noted during lytic replication (5, 6).A limited number of viral transcripts appear in the latent stage, whereas the viral genome produces all of the viral transcripts during the lytic phase (7). A key viral replication and transcription activator (RTA) switches latent infection to lytic replication (8). Studies have characterized multiple cellular signaling pathways and transcription factors required for RTA expression. Mitogenactivated stimuli or stresses initiate RTA expression through mitogen-activated protein kinase (MAPK) or stress-activated protein kinases (SAPK), respectively (9-14). Thereafter, RTA activates viral lytic transcription and replication. RTA binding sites in the KSHV genome and responsive KSHV promoters have been characterized (15,16); these studies revealed that most viral gene expression is not directly activated by RTA and requires additional cellular transcription factors. Based on the analysis of elements in the RTA, ORF45, and K8 promoters, multiple transcription factors, including c-Fos, c-Jun, Sp1, CREB, C/EBP, c-Myc, and ATF-2, are required for the expression of immediate early (IE) genes (11)(12)(13)(17)(18)(19); most of these transcription factors are the direct or indirect targets of MAPK pathways (20,21). Recently, nonconventional viral DNA elements, viral noncoding RNA, and viral proteins required for KSHV late transcription have been characterized (22)(23)(24)(25)(26). The viral lytic proteins ORF24, ORF31, and ORF34 assemble into a transcriptional activator complex (25), and ORF24 recruits RNA polymerase II to viral late promot-

Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease in the world, is affected by numerous extrinsic and intrinsic factors, including lifestyle, environment, diet, genetic susceptibility, metabolic syndrome and gut microbiota. Accumulating evidence has proven that gut dysbiosis is significantly associated with the development and progression of NAFLD, and several highly variable species in gut microbiota have been identified. The gut microbiota contributes to NAFLD by abnormal regulation of the liver-gut axis, gut microbial components and microbial metabolites, and affects the secretion of bile acids. Due to the key role of the gut microbiota in NAFLD, it has been regarded as a potential target for the pharmacological and clinical treatment of NAFLD. The present review provides a systematic summary of the characterization of gut microbiota and the significant association between the gut microbiota and NAFLD. The possible mechanisms of how the gut microbiota is involved in promoting the development and progression of NAFLD were also discussed. In addition, the potential therapeutic methods for NAFLD based on the gut microbiota were summarized.