Identification and functional characterization of miR-451a as a novel plasma-based biomarker for occult hepatitis B virus infection.

BACKGROUND: Numerous studies have indicated that miRNAs might play significant roles in the development of hepatitis B virus (HBV) infection. while the miRNAs in occult HBV infection (OBI) are still largely unknown. METHODS: Initially, 15 HBV infection-related miRNAs in plasma of 10 OBI and 10 healthy controls (HCs) was analyzed by qRT-PCR. Significantly dysregulated miRNAs were subsequently validated in another 64 OBI, 20HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Furthermore, the potential biological functions and molecular mechanisms of miR-451a in HBV infection were investigated using HBV-expressing hepatoma cell lines. RESULTS: Compared to HCs, plasma miR-451a and miR-340-3p were significantly up-regulated in OBI, ASC and CHB patients, while no significant difference was found among OBI, ASC and CHB patients. ROC curve analysis indicated that both plasma miR-451a and miR-340-3p could moderately distinguish OBI from HCs, with AUCs of 0.76 and 0.78, respectively. When combined, the differentiation efficiency of this miRNA panel was better, with an AUC of 0.82. While, they both could not specifically separate the stage of chronic HBV infection. Functional experiments showed that overexpression of miR-451a might suppress HBV replication and gene expression in hepatoma cell lines. Mechanistically, miR-451a might inhibit HBV replication and gene expression by directly targeting ATF2. CONCLUSIONS: A plasma panel, including miR-340-3p and miR-451a that might suppress HBV replication by targeting ATF2, has the potential as biomarkers for HBV infection. In the setting of blood donations, this panel would be more practical to moderately differentiate OBI in HBsAg-negative donors.

Identification and characterization of lncRNA AP000253 in occult hepatitis B virus infection.

BACKGROUND: Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. METHODS: The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. RESULTS: Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. CONCLUSIONS: AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

Circulating miRNA expression profile and bioinformatics analysis in patients with occult hepatitis B virus infection.

Emerging suggest that microRNAs (miRNAs) play vital roles in the occurrence and development of hepatitis B virus (HBV) infectious disease. However, miRNAs in occult hepatitis B virus infection (OBI), a special stage of HBV infection, remain largely unknown. Herein, we conducted this study to identify differentially expressed miRNAs and then to investigate the potential roles of these miRNAs in OBI. Plasma miRNA expression profiles of three OBI patients and three healthy controls were analyzed with high through-put miRNA sequencing technology. Altered expression of miRNAs was further confirmed with reverse transcription quantitative polymerase chain reaction (qRT-PCR). Finally, bioinformatics analysis was conducted to investigate the involved pathways and target genes for these differentially expressed miRNAs. Totally, 32 differentially expressed miRNAs were identified between OBI and healthy controls by miRNA sequencing (fold change ≥ 1.5, P < .1, and counts per million reads ≥ 1), including 16 downregulated and 16 upregulated miRNAs. Differential expression of hsa-miR-486-5p, -25-3p, and -92a-3p and -1-3p was further validated by qRT-PCR analysis, which was consistent with miRNA sequencing analysis. Moreover, these four miRNAs might distinguish OBI from HCs efficiently. Bioinformatics analyses indicated that the differentially expressed miRNAs were primarily involved in various biological processes related to gene expression and transcription, cell development and metabolism, protein modification and kinase activity regulation, as well as multiple signaling pathways such as PI3K/Akt signaling pathway. This study provided a global view of miRNA expression in plasma from OBI patients. These differentially expressed miRNAs might play important roles in the development of OBI, which provided intriguing insights into the screening and molecular mechanism of OBI.

Differential expression profile of long noncoding RNAs in chronic HBV infection: New insights into pathogenesis.

Increasing studies have revealed that long noncoding RNAs (lncRNAs) might play vital roles in the development and progression of various diseases including viral infectious diseases. However, the expression and biological functions of lncRNAs in chronic hepatitis B virus (HBV) infection remain largely unknown. Therefore, lncRNA microarray was performed to analyze the lncRNAs' and messenger RNAs' (mRNAs) expression profiles in liver tissues from patients with chronic HBV infection. Subsequently, a comprehensive bioinformatics analysis was conducted to investigate the potential functions of the differentially expressed genes. As a result, a total of 203 differentially expressed lncRNAs and 180 mRNAs were identified in chronic HBV infection. The expressions of five differentially expressed lncRNAs were further validated using quantitative real-time polymerase chain reaction. Gene ontology, pathway analysis, and gene set enrichment analysis revealed that differentially expressed lncRNAs might be mainly be involved in cytokine-cytokine receptor interaction and varied biotransformation processes, including fatty acid metabolism, amino acid metabolism, carbon metabolism, and drug metabolism. Additionally, coexpression networks between differentially expressed lncRNAs and mRNAs were constructed to reveal the hub regulator and analyze the functional pathways. This study provided an overview of lncRNA and mRNA expression in liver tissues from patients with chronic HBV infection. These differentially expressed lncRNAs might play crucial roles in the pathogenesis and progression of chronic HBV infection, which deserve further investigation.

Serum polybrominated diphenyl ether exposure and influence factors in blood donors of Wuxi adults from 2013 to 2016.

Polybrominated diphenyl ethers (PBDEs) have been used as brominated flame retardants worldwide and are correlated with extensive environmental pollution and human health concerns. This study is aimed at analyzing the concentrations of PBDEs and at evaluating their temporal trends among a population of blood donors (n = 33) over a 4-year period. A total of 132 serum samples were used for PBDE detection. Nine PBDE congeners were quantified in serum samples by gas chromatography with mass spectrometry (GC-MS). The median concentrations of Σ9PBDEs in each year were 33.46, 29.75, 30.85, and 35.02 ng/g lipid, respectively. Most of the PBDE congeners showed a downward trend from 2013 to 2014 and then increased after 2014. No correlations between age and PBDE congener concentrations were observed, while concentrations of each congener and Σ9PBDE were nearly always lower in females than in males, especially in BDE-66, BDE-153, BDE-183, BDE-190, and Σ9PBDE. We also found that the intake of fish, fruit, and eggs in the daily diet was related to the exposure level of PBDEs. Our results suggest that, as deca-BDE is still produced and used in China, diet is an important exposure pathway for PBDEs, and follow-up studies will be required to improve our understanding of the behaviors of PBDE isomers in humans and the exposure levels.

Systematic Review and Meta-Analysis of the Utility of Circular RNAs as Biomarkers of Hepatocellular Carcinoma.

Emerging studies have reported circRNAs were dysregulated in HCC. However, the clinical value of these circRNAs remains to be clarified. Herein, we aimed to comprehensively explore their association with the diagnosis, prognosis, and clinicopathological characteristics of HCC. PubMed, EMBASE, Web of Science, and Cochrane Library databases were comprehensively searched for eligible studies up to October 30, 2018. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. The pooled hazard ratio (HR) for overall survival (OS) and recurrence free survival (RFS) was calculated to assess the prognostic value. Ten studies on diagnosis, 12 on prognosis, and 23 on clinicopathology were identified from the databases. A total of 11 upregulated and 11 downregulated circRNAs showed an association with clinicopathological features of HCC. For the diagnosis analyses, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circRNAs for HCC were 0.74 (95%CI: 0.65-0.82) and 0.76 (95%CI: 0.70-0.81), 3.1 (95%CI: 2.5-3.8), 0.34 (95%CI: 0.25-0.47), and 9 (95%CI: 6-14), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.78-0.84), indicating moderate diagnostic accuracy. In stratified analyses, the diagnostic performance of circRNAs varied based on the source of control and specimen type. For the prognosis analyses, increased expression of upregulated circRNAs was associated with worse OS (HR: 3.67, 95%: 2.07-6.48), while high expression of downregulated circRNAs was associated with better OS (HR: 0.38, 95%: 0.30-0.48). In conclusion, this study reveals that circRNAs may serve as promising diagnostic and prognostic biomarkers for HCC. However, further investigations are still required to explore the clinical value of circRNAs.

[Effect of Tongdatang Serial Recipe on antipsychotic drug-induced galactorrhea-amenorrhea syndrome].

OBJECTIVE: To observe the clinical effect of self-formulated Tongdatang serial recipe (TDT) in treating antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS). METHODS: One hundred female schizophrenic patients with antipsychotic drug-induced GAS were selected and equally assigned to the treatment group and the control group at random. Both received antipsychotic drug-therapy, but combined with TDT and placebo respectively. The efficacy was evaluated by determining prolactin level before, 4 and 8 weeks after treatment. RESULTS: The treatment course was completed in 96% of patients. Therapeutic efficacy on the 49 patients of the treatment group was cured in 31 (63.3%), markedly effective in 11 (22.4%), effective in 4 (8.2%) and ineffective in 3 (6.1%), with total effective rate of 93.9%, while in 47 patients of the control group, the corresponding cases (%) was 0, 3 (6.4%) , 7 (14.9%) and 37 (78.7%), respectively, with the total effective rate of 21.3%. Prolactin levels in the two groups were insignificantly different before treatment, it reduced in the treatment group after treatment (P < 0.01), and the decrement in the treatment group was more significant than that in the control group (P < 0.05). CONCLUSION: Satisfactory effect could achieved by using TDT for treatment of antipsychotic drug-induced GAS.