Hepatocellular carcinoma (HCC) affects males in a significantly higher proportion than females and is one of the human cancers etiologically related to viral factors. Many studies provide strong evidence of the direct role that hepatitis B virus (HBV) plays in hepatic carcinogenesis, but the functions of HBV surface antigen (HBsAg) and X protein (HBx) in hepatocarcinogenesis through direct or indirect mechanisms are still being debated. We generated two HBV gene knock-in transgenic mouse lines by homologous recombination. HBsAg and HBx genes were integrated into the mouse p21 locus. Both male and female p21-HBx transgenic mice developed HCC after the age of 18 months; however, male p21-HBsAg transgenic mice began to develop HCC 3 months earlier. The expression of a number of genes related to metabolism and genomic instability largely resembled the molecular changes during the development of HCC in humans. ER-␤ (estrogen receptor-␤) was extremely up-regulated only in tumor tissues of male p21-HBsAg mice, providing genetic evidence that HBsAg might be the major risk factor affecting the gender difference in the causes of HCC. In conclusion, these mice might serve as good models for studying the different roles of HBsAg and HBx in early events of HBV-related hepatocarcinogenesis.

b Simeprevir (SMV), asunaprevir (ASV), daclatasvir (DCV), and sofosbuvir (SFV), which are newly developed direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection, are among the key components of anti-HCV regimens. Preclinical studies have identified inhibitory properties for some of these DAAs against organic anion transporting polypeptide 1B (OATP1B) functions. However, their details remain mostly uncharacterized. Because OATP1B1 and OATP1B3 play determinant roles in the pharmacokinetics of various drugs via their uptake into human hepatocytes, it is plausible that the inhibition of these OATP1Bs by a DAA would create a potential risk of drug-drug interaction, which has been an emerging concern in anti-HCV therapy. Accordingly, in the present study, we intended to clarify the inhibitory characteristics of newly developed DAAs toward OATP1B1 and -1B3 functions. The results of our coincubation inhibition assays have shown that all tested DAAs could inhibit OATP1B1 functions and that SMV, ASV, and DCV (to a lesser extent), but not SFV, exhibited long-lasting preincubation inhibitory effects on OATP1B1 functions. It was also found that the preincubation inhibitory effects of SMV and ASV could augment their coincubation inhibition potency. Furthermore, significant, but differential, inhibitory effects of the DAAs on the OATP1B3 function were identified. To summarize, our results clearly show that the newly developed DAAs are newly identified OATP1B1 and OATP1B3 inhibitors with distinctive interaction properties. It is believed that these inhibition profiles will provide essential information to all concerned parties with respect to the clinical significance of DAA-mediated inhibition of OATP1Bs in anti-HCV therapy.

While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37). Developed via the cell conditionally immortalization method, these cells exhibited excellent proliferative ability at 33 °C. However, when cultured at 37 °C, HBPC/ci37 cells showed a differentiated phenotype that was marked by morphological alterations and increases in several pericyte-enriched marker mRNA levels, such as platelet-derived growth factor receptor β. It was also found that HBPC/ci37 cells possessed the facilitative ability of in vitro BBB formation and differentiation into a neuronal lineage. Furthermore, HBPC/ci37 cells exhibited the typical "reactive" features of brain pericytes in response to pro-inflammatory cytokines. To summarize, our results clearly demonstrate that HBPC/ci37 cells possess the ability to perform several key brain pericyte functions while also showing the capacity for extensive and continuous proliferation. Based on these findings, it can be expected that, as a unique human brain pericyte model, HBPC/ci37 cells have the potential to contribute to significant advances in the understanding of human brain pericyte physiology and pathophysiology.

Retinoblastoma (RB) is a childhood malignancy caused by inactivation of the RB gene, with neuron-specific enolase (NSE) levels considered as its diagnostic marker. MicroRNAs (miRNAs) have been proven to play a significant role in multiple physiological and pathological processes and several miRNAs were identified as tumor biomarkers in recent studies. In the present study, 65 plasma samples were collected from RB patients and 65 samples from healthy individuals to serve as controls. The miRNA levels were measured via quantitative reverse transcription-polymerase chain reaction and their association with RB was assessed by statistical data analysis and receiver operating characteristic curves. Plasma miRNA (miR)-320, miR-let-7e and miR-21 levels were downregulated in the patient samples, the areas under the curves (AUCs) were 0.548–0.660, whereas the AUCs of combined classifiers were ≥0.990. The plasma miRNA levels, particularly of miR-320, were found to be of value in RB diagnosis and may be considered as novel diagnostic biomarkers.

Emerging evidence have illustrated the vital roles of long noncoding RNAs (lncRNAs) in glioma. Nevertheless, the majority of their roles and mechanisms in gliomagenesis are still largely unclear. In this study, we investigate the roles of lncRNA CASC9 on glioma tumourigenesis and authenticate its potential mechanisms. Results manifested that CASC9 was highly expressed in glioma specimens and cells, moreover, the ectopic overexpression was correlated with glioma patients’ clinic. Functional studies found that siRNA‐mediated CASC9 silencing inhibited the proliferative ability, invasion in vitro, and impaired the tumour growth in vivo. Mechanical studies revealed that miR‐519d both targeted the 3′‐UTR of CASC9 and STAT3 mRNA, which was identified by luciferase reporter assay and RNA immunoprecipitation (RIP). Moreover, chromatin immunoprecipitation (ChIP) and luciferase reporter assay revealed that STAT3, an oncogenic transcription factor, could bind with the promoter of CASC9 and activate its transcriptional level. In conclusion, our results concluded that CASC9 promotes STAT3 expression via sponging miR‐519d, in return, STAT3 activate CASC9 transcription, forming a positive feedback loop of CASC9/miR‐519d/STAT3. The novel finding provides a potential therapeutic target for glioma.