Abstract:Chronic hepatitis C (CHC) is a global health problem, which is prevalent all over the world. China is a low epidemic area. Hepatitis C virus (HCV) is mainly transmitted through blood, and nowadays, intravenous drug addicts are the key population for the prevention and treatment of hepatitis C. HCV has multiple genotypes and gene subtypes, and the distribution of these genotypes and gene subtypes varies significantly among the regions of the world. Nowadays, the treatment of hepatitis C has entered the era of direct-acting antiviral agents, which have high efficacy and safety in the general population. However, when special populations use direct-acting antiviral agents to treatment hepatitis C, we don't know how its efficacy and safety will be. The special populations include children, adolescents, drug users, HCV/HBV co-infected patients, HCV/HIV co-infected patients, and patients who have comorbidity of HCV and chronic kidney disease. This review will discuss the efficacy and safety of using direct-acting antiviral agents to treat hepatitis C in these special populations.

The piperlongumine is a tertiary amine amide alkaloid, which is mainly found in the roots of the Piper family like long piper (Piper longum L.) and tumor-like piper (Piper tuberculatum Jacq). It has a variety of pharmacological activities, such as anti-platelet aggregation, anti-inflammatory and anti-tumor and its derivatives also have a variety of activities. In this paper, the research progress on the structural modification and bioactivity of pharmacological effects of the piperlongumine amide is reviewed, which provides a reference for the further study of amides.

Abstract: In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus （HCV）, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of an excerpt of Society for Maternal-Fetal Medicine Consult Series #56: Hepatitis C in pregnancy—updated guidelines: Replaces Consult Number 43, November 2017 is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy.

Objective To evaluate the effectiveness of the intervention on preventing mother to child transmission of HIV and identify the influencing factors.Methods The data regarding the pregnant women and their infants were collected,including demographic characteristics,pregnancy and delivery,access to antiviral therapy,HIV infection status at age 18 months and survival of infants between 2002 and 2013 through follow-up,Multivariate logistic regression model were used to identify the influencing factors.Results By the end of 2013,a total of 8 621 554 pregnant women received HIV test,among them 2 264 were infected with HIV.The positive rate of HIV is 0.03％.The HIV positive rate decreased year by year (x2=4.871,P=0.027).A total of 1 530 infants were born from 2002 to 2013,among them 1 384 survived and 92 died at age of 18 months,and 54 were lost for follow up.Sixty infants were tested to be HIV-positive,1 324 infants were tested to be HIV-negative.The mother to child transmission rate was 4.34％,the corrective mother to child transmission rate was 6.33％.Receiving HIV prevention service in early pregnancy (OR=0.26,95％ CI:0.09-0.77),standardized antiviral therapy OR=0.42,95％CI:0.21-0.82),artificial feeding (OR=0.06,95％CI:0.02-0.21) might be the mam protective factors,episiotomy on delivery (OR=3.91,95％ CI:1.74-8.80) might be the risk factors.Conclusion The HIV tested positive rate remained to be low and decreased year by year in pregnant women in Henan,but the mother to child HIV transmission rate was high.It is necessary to improve the prevention of mother to child HIV transmission.

OBJECTIVETo study the expression of recombinant human SCF-TPO fusion protein and its biological function.

METHODSFour primers were designed according to known sequences of TPO and SCF. The functional amino acid domains of TPO and SCF were amplified by RT-PCR from fetus hepatocytes, respectively. The expression plasmid pET32a/SCF-TPO was constructed by VOE gene fusion technique and expressed in E. coli BL21(DE3) plysS as inclusion body after isopropyl-beta-D-1-thiogalactopyranoside (IPTG) induction. The fusion protein was tested by SDS-PAGE and Western blot. The biological functions of SCF-TPO fusion protein in MO7e cells was investigated by MTT method after purification with metal chelating chromatography.

RESULTSThe high expression SCF-TPO fusion protein was obtained, reaching up to 30% of the total cellular protein. Western blot verified the correct fusion expression and MTT results showed the growth promoting effect of the SCF-TPO fusion protein on MO7e cells, with a higher promoting activity at 100 ng/ml.

CONCLUSIONSExpressed SCF-TPO fusion protein after renaturation has biological activity in promoting the proliferation of MO7e cells.

Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; genetics ; physiology ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; genetics ; Genetic Vectors ; Humans ; Recombinant Fusion Proteins ; genetics ; metabolism ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cell Factor ; genetics ; metabolism ; physiology ; Thrombopoietin ; genetics ; metabolism ; physiology

In order to investigate the expression of heavy chain of HLA-B * 2705 in prokaryotic system and identify its activity, the extra-membrane gene fragment of HLA-B * 2705 was amplified from full-length HLA-B*2705 cDNA by PCR and cloned into pGEM-T vector. After identification by sequencing, the prokaryotic expressing vector pET32a (+)-B * 2705 was constructed. The antigenic activity of expressed protein was identified by Western blot and antibody blocking reaction. The results indicated that the fused HLA-B * 2705 protein expression with high efficiency was obtained. The expressed product was more than 50% of the total bacteria protein. The antigenic activity of expressed protein was confirmed by Western blot and antibody blocking reaction. It is concluded that HLA-B * 2705 fusion protein are obtained as basis for the further studies.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; genetics ; HLA-B27 Antigen ; classification ; genetics ; immunology ; metabolism ; Humans ; Immunoglobulin Heavy Chains ; genetics ; immunology ; metabolism

After search at hematopoietic stem cell banks for transplant donors, there may be several donors matched with given standards. To determine the most appropriate donor for a specific patient, the potential donors were analyzed and compared by three methods. The first is cross-reactive group (CREG) antigens, which defined as the public antigens that shared specific serological reaction patterns. The second is residue match theory, which concerned the three residues oriented upward toward the T-cell receptor. The third is comparing HLA three-dimensional structure models. The results of the three methods were not completely accorded in our case. However, some less matched donors could be excluded from the candidates and the range of selection was further reduced. It is concluded that combined application of three methods would contribute in selecting donor for hematopoietic stem cell transplantation in clinics.
Cross Reactions ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Testing ; Humans ; Tissue Donors

The purpose of the research is to provide a new standard for matching of HLA three-dimensional structure, and summarize the major permissible mismatch and immunogenic mismatch antigens. The molecular modeling method was used to create HLA molecular structures by Swiss Model Server, and the comparison of the differences among the alleles was done by SPDV software with the function of iterative magic fit. The results were recorded by relative mean square deviation (RMSD, nm). The differences among alleles were scattered below 0.06 nm for HLA-A and -B molecules, and below 0.03 nm for HLA-DRB1 molecules. On the basis of the statistical analysis, when RMSD is greater than 0.04 nm for -A and -B molecules and 0.02 nm for -DRB1 molecules, the difference is meaningful and can be related with graft versus host disease. When RMSD is lower than 0.02 nm for -A and -B molecules and 0.01 nm for -DRB1 molecules, the difference is decided unmeaningful. From the data, the permissible mismatch and immunogenic mismatch alleles within HLA-A, HLA-B and HLA-DRB1 molecules were summarized. Three-dimensional structure matching is a new area in the transplantation field, much research should be done in the future.

To probe into the expression of alpha subunit for IL-6R at both mRNA and protein levels in human leukemic cells and to discuss its implication in targeted treatment for leukemia with recombinant IL-6-PE40 exotoxin fusion protein mediated by IL-6/IL-6R system, semi-quantitative RT-PCR, sequencing and FCM were used to analyze the gene and protein expression levels of alpha subunit for IL-6R in leukemic cells. Our results showed that not only mRNA but also protein of alpha subunit for IL-6R are highly expressed in the myelogenous leukemic cell lines, the relative expression levels of mRNA were KG-1(1.22) > (1.02) > U266(1.00) > U937(0.99) > HL-60(0.76). Among lymphoblastic leukemic cell lines, Raji expressed a certain amount of alpha subunit mRNA (0.77), whereas its alpha subunit protein was not detected. Expression of alpha subunit mRNA and protein were negative in lymphoblastic leukemic cell lines, HuT28 and CEM, and chronic myelocytic leukemic cell line K562. These results correlate with those of FCM highly. Noteworthily, normal human peripheral blood mononuclear cells expressed hardly protein of IL-6R alpha subunit. So this study provides sufficient experimental evidence that the targeted treatment by recombinant IL-6-PE40 can specifically kill leukemic cells highly expressing IL-6R without toxicity to normal hematopoietic cells.
Base Sequence ; DNA, Neoplasm ; analysis ; Gene Expression ; HL-60 Cells ; Humans ; K562 Cells ; Leukemia ; metabolism ; Molecular Sequence Data ; Protein Subunits ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; Receptors, Interleukin-6 ; biosynthesis ; genetics ; Tumor Cells, Cultured ; U937 Cells

OBJECTIVETo investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia.

METHODSHyperthermic HepG2 cell models established by exposure of the cells to 42 degrees celsius; for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed.

RESULTSROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001).

CONCLUSIONThe intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.

HSP90 Heat-Shock Proteins ; metabolism ; Hep G2 Cells ; Hot Temperature ; Humans ; Proteasome Endopeptidase Complex ; metabolism ; RNA, Small Interfering ; genetics ; Reactive Oxygen Species ; metabolism ; Up-Regulation