B型肝炎ウイルスGenotype CにおけるX領域Codon38変異は発癌のリスクファクターである

BACKGROUND/AIMS: The hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, the HBV X gene, which encodes the pleiotropic transactivator HBx, has also been associated with the development of HCC. In this study, we investigated whether nucleotide changes in the X gene of genotype C are associated with the development of HCC. METHODS/RESULTS: We sequenced the X gene in age- and sex-matched 39 HBV-infected patients with HCC and 36 HBV-infected patients without HCC. A novel nucleotide change that resulted in a proline to serine substitution at codon 38 in HBx (codon-38 change) was preferentially found in patients with HCC. Then, sera were collected from a new group of age- and sex-matched 52 patients with HCC and 51 patients without HCC. In this cohort also, the codon-38 change was associated with HCC. Multiple logistic regression analysis showed the prevalence of the codon-38 change was significantly associated with HCC in all patients (P=0.001, odds ratio: 4.89). CONCLUSION: The codon-38 change in genotype C is an independent risk factor for the development of HCC and may serve as a useful molecular marker for predicting the clinical outcomes in patients infected with HBV

Alkylated alkali lignin for compatibilizing agents of carbon fiber reinforced plastics with polypropylene

金沢大学理工研究域生命理工学系As an alternative to petroleum-based compatibilizing agents, we developed lignin derivatives for compatibilizing agents of carbon fiber-reinforced plastics that have thermoplasticity. In this study, alkyl chains were introduced into alkali lignin at various ratios to optimize the compatibility of the lignin derivatives with both polypropylene and carbon fiber. The interfacial shear strength between the two materials was improved from 8.2 to 17.2 MPa by mixing with the optimized lignin derivative. The value is comparable to that achieved with a typical petroleum-based compatibilizing agent (18.3 MPa).Embargo Period 6 monthsThis paper has supplementary information

The characteristic changes in hepatitis B virus x region for hepatocellular carcinoma: a comprehensive analysis based on global data.

Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the distribution of those mutations in different disease phases and genotypes.HBx sequences downloaded from an online global HBV database were screened and then classified into Non-HCC or HCC group by diagnosis information. Patients' data of patient age, gender, country or area, and viral genotype were also extracted. Logistic regression was performed to evaluate the effects of mutations on HCC risk.1) Full length HBx sequences (HCC: 161; Non-HCC: 954) originated from 1115 human sera across 29 countries/areas were extracted from the downloaded 5956 HBx sequences. Genotype C occupied 40.6% of Non-HCC (387/954) and 89.4% of HCC (144/161). 2) Sixteen nucleotide positions showed significantly different distributions between genotype C HCC and Non-HCC groups. 3) Logistic regression showed that mutations A1383C (OR: 2.32, 95% CI: 1.34-4.01), R1479C/T (OR: 1.96, 95% CI: 1.05-3.64; OR: 5.15, 95% CI: 2.53-10.48), C1485T (OR: 2.40, 95% CI: 1.41-4.08), C1631T (OR: 4.09, 95% CI: 1.41-11.85), C1653T (OR: 2.58, 95% CI: 1.59-4.19), G1719T (OR: 2.11, 95% CI: 1.19-3.73), and T1800C (OR: 23.59, 95% CI: 2.25-247.65) were independent risk factors for genotype C HBV-related HCC, presenting different trends among individual disease phases. 4) Several genotype C HCC risk mutations pre-existed, even as major types, in early disease phases with other genotypes.Mutations associated with HCC risk were mainly located in HBx transactivation domain, viral promoter, protein/miRNA binding sites, and the area for immune epitopes. Furthermore, the signatures of these mutations were unique to disease phases leading to HCC, suggesting molecular counteractions between the virus and host during hepatocarcinogenesis

A Hot Water Extract of Curcuma longa L. Improves Fasting Serum Glucose Levels in Participants with Low-Grade Inflammation: Reanalysis of Data from Two Randomized, Double-Blind, Placebo-Controlled Trials

The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation

Flowchart for screening HBx sequences downloaded from an online global database.

<p>We downloaded HBx sequences from Hepatitis Virus Database (HVDB, <a href="http://s2as02.genes.nig.ac.jp/" target="_blank">http://s2as02.genes.nig.ac.jp/</a>). The version we exploited was DDBJ Rel. 95, containing 5956 HBx sequences in total. Sequences were then screened successively by attached information such as publication, origin, and diagnosis. Sequences enrolled should be 1) Full length HBV X sequence; 2) human sera origin; and 3) with diagnosis information and thus could be classified to non-HCC or HCC group. Finally 1115 full length HBx sequences (HCC, 161; and Non-HCC, 954) from 57 publications were extracted for further analyses.</p

Seven nucleotide mutations of HBx sequences were independent risk factors for genotype C HBV-related <b>HCC</b>.

<p>^aMutated nucleotides are shown in bold.</p><p>B cell epitope: region (aa positions 29–48); BH3-like motif: region (aa positions 116–132); Box α, region (nt1646-1668); C/EBP, CCAAT/enhancing binding protein, region (nt1643-1658); CP, core promoter, region (nt1613-1849); Enh2: enhancer 2, region (nt1636-1744); HNF3, hepatocyte nuclear factor 3, region (nt1713-1723); NRE, negative regulatory element, region (nt1611-1634); T-cell epitope: region (aa positions 116–127).</p><p>Seven nucleotide mutations of HBx sequences were independent risk factors for genotype C HBV-related <b>HCC</b>.</p

HCC risk mutations in genotype C sequences across different disease phases.

<p>We checked the distribution of HBV genotype C HCC risk mutations among sequences from different disease phases (ASC, 18; CHB, 38; LC, 27; HCC, 144). Those mutations showed characteristics among different phases: 1) except three mutations (1479T, 1631T, and 1800C) all the other mutations pre-existed in ASC, among which 1383C and 1719T were most pronounced. More than 50% ASC possessed either one of these two mutations and 42% ASC possessed both; 2) the frequency of four mutations (1485T, 1631T, 1762T, and 1764A) showed an increasing trend accompanied with the disease progression though the changes among groups were not significant (Jonckheere-Terpstra trend test, <i>P</i> > 0.05); and 3) ratios of 4 mutations (1383C, 1479C, 1479T, and 1719T) fluctuated among different disease phases. No mutants were observed in the cases denoted by asterisks.</p

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and HBx-overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of ELAVL1 resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in ELAVL1-knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment