Differential expression profile of hepatic circular RNAs in chronic hepatitis B.

CircRNAs exert gene regulatory effects by sequestering target microRNAs (miRNAs) and play a vital role in the onset and development of disease. Until recently, little has been known about the expression, regulation and biological function of circRNAs in both health and chronic hepatitis B (CHB).To identify hepatic circRNAs associated with CHB, we performed RNA sequencing using liver biopsies from untreated CHB patients and controls. We then established a bioinformatics pipeline for identification of CHB-associated circRNAs and in silico analysis of the circRNA-miRNA-mRNA pathways. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to confirm these results. The profiles of hepatic circRNA expression were significantly different in CHB compared with controls, with a total of 99 dysregulated circRNAs identified to be correlated with CHB. Computational analysis of the circRNA-miRNA-mRNA pathways revealed a large number of miRNAs (665), which were putatively targeted by the differentially expressed hepatic circRNAs. Interestingly, four of the predicted CHB-related circRNA-miRNA-mRNA pathways were found to be involved in the pathogenesis of HBV infection and progression of HBV-associated liver disease. Among these pathways, regression analysis of gene expression revealed a strong positive correlation between hsa_circ_0000650 and TGFß2 and a negative correlation between hsa_circ_0000650 and miR-6873-3p, which hinted that hsa_circ_0000650 interacted with TGFß2 mediated by miR-6873-3p. This study firstly demonstrates that patients with CHB present different profiles of hepatic circRNAs and circRNA/miRNA interactions. Thus, circRNAs have promise as novel mechanisms underlying the pathogenesis and progression of CHB.

Systematic review and meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion.

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.

NOVEL GENETIC FINDINGS IN A CHINESE FAMILY WITH EARLY-ONSET FEMALE-RELATED TYPE 2 DIABETES.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

[Expression and regulation of milk protein gene in mammalia].

On the basis of introducing the structures and relations of evolution in milk protein genes, the factors involved in gene expression including cis-acting elements, trans-acting factors as well as induction of hormones were discussed. Finally the applicable prospect of mammary gland as a bioreactor was estimated.

[On the central inhibition action of tetrahydroberberine without relevance to GABA receptors].

Using an earthworm (Eisenia foetida) dorsal muscle preparation, it was shown that tetrahydroberberine (THB, 10(-7)-10(-4) mol/L) did not affect both GABA and ACh receptors. DA receptor antagonist haloperidol (HAL) also exerted no effect. Owing to the blocking action of isonicotinyl hydrazine (INH) and thiosemicarbazide (TSC) on biosynthesis of GABA, and of picrotoxin (PT) and bicuculline (Bic) on the GABA-BZ receptor complex mediated transmission, all these agents could induce convulsion in mice. This action could be antagonized by amino- oxyacetic acid (AOAA) and benzodiazepine (BZ), but not by DA receptor antagonists THB and HAL. All the above observations indicate that the GABA inhibition is not involved in the central action of THB.

[Effects of epidermal growth factor on growth and differentiation of rat granulosa cells].

It was known that epidermal growth factor (EGF) plays an important role in the regulation of reproduction. The present study was undertaken to investigate the effect of EGF on the proliferation and differentiation of cultured rat granulosa cells. The results showed that EGF inhibited the 3H-TdR incorporation into DNA of granulosa cells, while the progesterone production was increased due to enhanced 3 beta-HSD activity. Radioreceptor assay (RRA) suggested that there were specific receptors for EGF on the granulosa cell with a Kd of 1.83 +/- 0.30 x 10(-8) mol/L and a Bmax of 1.75 +/- 0.29 x 10(4) sites/cell. Using method of immunohistochemistry, no EGF-like immunoreactivity was found in the granulosa cells at different age or different estrous cycle, but in the theca folliculi, interstitium and corpus luteum. These results suggest that EGF can regulate the growth and differentiation of the granulosa cells in the course of maturation of the folliculi and granulosa cells.

Effects of monoclonal antibody anti-EGF receptor on human nasopharyngeal carcinoma cell and other tumor cells.

Three anti-EGF receptor MoAbs were used in these studies. Administration of MoAbs 3 and 176 inhibited tumor formation in nude mice by CNE-2, a poorly differentiated nasopharyngeal carcinoma cell line and A431, an epidermoid carcinoma cell line. When the same MoAbs were used in treatment against HeLa, a cervical carcinoma, tumor growth was not affected. The number of EGF receptors and apparent dissociation constants for 125I-EGF on CNE-2 and A431 was 1.3 x 10(5)/cell (Kd 7.7 x 10(-8) mol/L) and 1.4 x 10(6)/cell (Kd 2.4 x 10(-9) mol/L), respectively. Both MoAbs 3 and 176, capable of competing with EGF for receptor binding, showed significant tumor growth inhibition. MoAb 101 was incapable of blocking the binding of EGF to its receptor, and not as effective as MoAbs 3 and 176 in tumor growth inhibition. Our observation is that the MoAb anti-EGF receptor is cytostatic rather than cytocidal, in vitro against CNE-2 and A431.

Growth inhibition of human nasopharyngeal carcinoma in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies.

Monoclonal antibodies (MoAbs) were developed against epidermal growth factor (EGF) receptor on the human epidermoid carcinoma cell line A431. The A431 antigen recognized by the MoAbs has an apparent molecular weight of approximately 170,000, with the same molecular weight as the CNE-2 cell line (poorly differentiated nasopharyngeal carcinoma). Administration of anti-EGF receptor MoAbs inhibited tumor formation, caused by the CNE-2 and A431 cell lines, in athymic mice. When the same MoAbs were used in therapy against Tca8113 (a human tongue carcinoma) and HeLa cells (a human cervical carcinoma), tumor growth was not affected. The number of EGF receptors and the apparent dissociation constants for 125I-EGF on CNE-2 and A431 were 1.3 x 10(5)/cell (Kd 7.7 x 10(-8) M) and 1.4 x 10(6)/cell (Kd 2.4 x 10(-9) M), respectively. Three anti-EGF receptor MoAbs were used in these studies. MoAbs 3 and 176, capable of competing with EGF for receptor binding, showed significant tumor growth inhibition. MoAb 101 was incapable of blocking the binding of EGF to its receptor and was not as effective as MoAbs 3 and 176 in tumor growth inhibition. Our observation is that in vitro, MoAb anti-EGF receptor is cytostatic, rather than cytocidal, against CNE-2 and A431.

Benzodiazepine receptors in isolated adrenal glomerulosa cells.

In our experiments the isolated rat adrenal glomerulosa cells displayed peripheral-type benzodiazepine receptors, which could bind to [3H] PK11195 with an apparent equilibrium dissociation constant (KD) of 9.4 +/- 2.8 nmol/L and a maximal binding capacity (Bmax) of 5.6 +/- 1.8 pmol/10(6) cells. The effects of five ligands: PK11195, Ro5-4846, flunitrazepam, diazepam and clonazepam on aldosterone secretion responses of isolated glomerulosa cells to angiotensin II or extracellular potassium ions were observed. The logarithm of EO50 for these ligands as stimulators was well correlated with the logarithm of their Ki value for [3H] PK11195 binding, suggesting that the stimulative effects might be mediated by the benzodiazepine receptor in isolated glomerulosa cells.

[Effects of an endogenous GABA receptor binding inhibitor on rat blood pressure].

The GABA receptor agonists GABA (400 micrograms icv) and muscimol (1 microgram icv) induced hypotension in urethane-anesthetized rats, while the GABA receptor antagonist bicuculline (2 micrograms icv) elicited hypertension. An endogenous GABA receptor binding inhibitor (1 mg), prepared from bovine cerebellum, showed bicuculline-like hypertensive action in a dose-dependent manner. It was antagonized by icv muscimol, but not by the alpha 2-adrenoceptor agonist clonidine. These in vivo results agree quite well with our previous in vitro receptor binding assay experiments.