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SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.
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2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus ( SARS-CoV) and middle east respiratory syndrome-coronavirus ( MERS-CoV) . At present, there is no spe-cific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019-nCoV pneu-monia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.
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2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019-nCoV pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.
ABSTRACT
2019 novel coronavirus (2019-nCoV) is a new member of coronavirus family that can cause serious respiratory diseases after the emergence of severe acute respiratory syndrome-coronavirus (SARS-CoV) and middle east respiratory syndrome-coronavirus (MERS-CoV). At present, there is no specific antiviral drug targeting 2019-nCoV. In facing of the increasingly serious epidemic of 2019 novel coronavirus pneumonia and the urgent needs in drug treatment strategies, this paper reviewed the current research situation and progress in antiviral treatment for the newly identified disease.
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Zika virus belongs to the family Flaviviridae, genus Flavivirus and is mainly transmitted to humans by Aedes. The outbreak of Zika virus infection in South America in 2015 raised worldwide health concern due to the increasing incidence of microcephaly, Guillain-Barre syndrome and myelitis, although most of the patients were asymptomatic. Here, to further understand and elucidate the pathogenic mechanism of Zika virus infection-associated myelitis, this review summarized the latest advance in biological characteristics, transmission and treatment of Zika virus infection as well as the related case reports and possible mechanisms.
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Zika virus belongs to the family Flaviviridae, genus Flavivirus and is mainly transmitted to humans by Aedes. The outbreak of Zika virus infection in South America in 2015 raised worldwide health concern due to the increasing incidence of microcephaly, Guillain-Barre syndrome and myelitis, although most of the patients were asymptomatic. Here, to further understand and elucidate the pathogenic mechanism of Zika virus infection-associated myelitis, this review summarized the latest advance in biological character-istics, transmission and treatment of Zika virus infection as well as the related case reports and possible mechanisms.
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Objective To identify hepatitis B virus X-interactive proteins by comparative proteomics method and to understand the molecular mechanism of HBx in the development of hepatocellular carcinoma(HCC).Methods Two-dimensional gel electrophoresis(2-DE)was used to separate the total proteins of HBx-transfected human hepatoma cell lines HepG2-Px and its parental cell lines HepG2-P_0.PDQuest software was applied to analyze 2 DE images.The differentially expressed protein spots between the two cell lines were identified by matrix-assisted laser desorptionionization time of flight mass spectrometry(MALDI-TOF-MS)and electrospray ionization tandem mass spectrometry(ESI-Q-TOF).Then,the differential expression levels of some identified proteins were determined by Western blot.The data were compared using t test.Results The well-resolved,reproducible 2-DE patterns of HepG2-Px and HepG2-P_0 total proteins were established.A total of 32 differential proteins were identified in HepG2-Px cell,including 25 up-regulated proteins,such as heat shock protein(HSP)90AB1,Bcl-2 associated athanogene(BAG)-2,nucleophosmin(B23),chloride intracellular channel(CLIC)-1,matrix metalloproteinase(MMP)-3,melanoma antigen(MAGE)-12,and 7 down-regulated proteins,such as Wnt-5a.The differential expression levels of some proteins between the two cell lines were confirmed by Western blot analysis.Conclusions Most of the identified proteins are involved in many processes,such as transcription,signal transduction,cell proliferation,cell cycle regulator,apoptosis,DNA repair,metabolisms and immunity.These differential proteins may play a role in tumor genesis and HC development.The data are valuable for further study on the role of HBx in human hepatocellular carcinoma.
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<p><b>BACKGROUND</b>To study the effect and safety of tissue specific gene therapy of suicide gene for lung adenocarcinoma.</p><p><b>METHODS</b>Retroviral vector of G1CEACDNa contained a carcinoembryonic antigen (CEA) promoter regulated cytosine deaminase expression cassete (CEA/CD). By means of infection of virus, tissue specific expressing vectors and non-specific expressing vectors were transfected into A549 cell, which was CEA-producing lung adenocarcinoma cell line and then xenografted in nude mice, and the anti-tumor effect was evaluated. Then the retrovirus was injected directly into the tumor mass on nude mice, and the sensitivity of the xenograft to G1CEACDNa/5-fluorocytosine (5-FC) and the side effects were observed.</p><p><b>RESULTS</b>(1) After transfected and untransfected A549 cells were implanted into nude mice, there was no difference in tumor formation among all the groups. (2) After 5-FC administration, the tumor transfected with tissue-specific gene displayed a higher sensitivity to the drug than those treated with non-specific in vitro gene-therapy. (3) The tumor-bearing nude mice were randomized in a blind manner based on comparable size to receive the supernatant of recombinant retrovirus G1CEACDNa followed by 5-FC, and significant growth suppression could be observed. (4) Comparing to the group with injection of 5-fluorouracil (5-FU) alone, tissue-specific suicide gene therapy showed lower suppression to bone marrow.</p><p><b>CONCLUSIONS</b>The results suggest that tissue-specific suicide gene therapy may play an important role in individual treatment of lung cancer.</p>
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Presently, there are 3 problems in the study of human embryonic pluripotent stem cells: short of materials, complicacy of culture system and spontaneous differentiation. Both basic research and clinical application of human embryonic pluripotent stem cells were hindered by these 3 basic problems. New embryonic pluripotent stem cells should be established by combining nucleus transfer and plasma reprograming, and their possible mechanisms and key factors need further study. The culture system should be simplified and cell differentiation must be inhibited when pluripotent stem cell is cultured. When pluripotent stem cells are induced to differentiation, combination of several methods should be used to induce and select specific cell lineages, and the morphology and function of the target cell must be evaluated.
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The germ cell lineage in the mouse is established during gastrulation;sex determination is achieved after germ cell migrating to the site of the future gonads. Germ cells proliferate indefinitely when cultured in vitro . Human embryonic germ(EG) cells have been recently established;these immortalized EG cells are chromosomally stable and pluripotent, raising the hope that their differentiation can be directed to specific cell types, which may be of value in the clinical treatment of degenerative diseases.
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The Oct4,a POU transcription factor belongs to class Ⅴ of POU proteins, is expressed in mouse totipotent embryonic stem and germ cells. Oct4 plays a critical role in maintaining pluripotency of stem cell when it differentiates into a trophectoderm lineage at early stage of mouse embryo. Oct4 expression appears to be regulated by a positional effect as well as specific regulating elements of Oct4 such as proximal enhancer (PE) and distal enhancer (DE). Oct4 has both repression and activation effects in regulating transcription,and the activation has 3 models: distance dependent transactivation, conformational transactivation and Oct4 dimers dependent transactivation.
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Aim To screen out the antigenic sequences from HCV core protein random peptide libraries displayed on phage and to explore a new way to screen the viral antigens. Methods The anti-HCV core antibody-positive serum was used to screen antigenic peptides from the HCV core protein random peptide libraries displayed on phage for 4 rounds. Detection of numbers of positive clones, positive rate of insertion of HCV random DNA and positive rate of hybridization with HCV core probes were used to evaluate the screening effects. The DNA sequences of 7 selected clones with positive hybridization were determined and analysed. Results Six out of 7 sequences are HCV core protein sequences, in which 5 were perfectly displayed,and one was possibly displayed. These sequences included several major HCV core antigenic epitopes. The remaining one was E.coli nrfa gene. Conclusion The phage display technique can be applied to study the viral antigenic peptides with the advantages of simple, accuracy and rapidity.
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Objective:To clone and express the full length cDNA of human CD38. Methods:The full length cDNA of the human CD38 antigen was amplified from total RNA of Daudi cell by RT-PCR, and it was inserted into pGEM-T. The validity on the sequences was confirmed by automatic DNA sequencing. Inserting the valid CD38 gene into pcDNA3.1(+) plasmid to obtain recombinant mammalian expression vector pcDNA3.1(+)/CD38Z; Using lipofectin gene transfer technique system, recombinant expression vector containing CD38 gene was transfected into COS7 cells. The expression of CD38 molecules on the surface of COS7 cells was detected by FACS and immunohistochemical technique. Results:DNA sequencing showed that the cloned full length cDNA sequence was identical with reported. The result of FACS and immunohistochemical technique indicated that CD38 molecules were expressed on the surface of COS7 cells. Conclusion:The full length cDNA of human CD38 is obtained, recombinant mammalian expression vector pcDNA3.1(+)/CD38Z is successfully constructed, and the CD38 molecules is expressed on the surface of COS7 cells,this may facilitate studies on the biochemistry and function of CD38 antigen.
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Objective To investigate pathogene city, replication and expression of hepatitis G virus (HGV) in rhesus monkey infected with HGV RNA genome or HGV RNA positive sera. Methods A full length cDNA clone of HGV was constructed. Rhesus monkey BY1 was inoculated intrahepatically with genomic RNA from this HGV clone resulted in viral replication. HGV RNA positive sera from BY1 were intravenously inoculated into rhesus monkeys BM1, and sera from BM1 were intravenously inoculated into BB1 in series. Sera were collected weekly or bi weekly and liver biopsies were performed regularly. RT PCR, in situ hybridization and immunological, serological, histological assays were carried out to study the infectivity and pathogenecity of HGV. Results The serological and pathological results indicated that all of the 3 rhesus monkeys developed HGV viremia and had slightly elevated alanine transaminase levels (up to 418 IU/ L) during the period of experiment. HGV RNA became positive at the 3 rd , 8 th and 3 rd week post inoculation in the animals BY1, BM1 and BB1 respectively, and existed up to 21 weeks. The histology, immunohistochemnistry, and in situ hybridization in the liver tissues of the inoculated animals also showed that there was a mild hepatitis with HGV E2 expression in cytoplasm of hepatocytes. RT PCR and quantitative PCR showed that HGV could replicate in liver.Conclusions The genomic RNA from HGV full length cDNA is infective to the rhesus monkeys resulting in mild hepatitis. Infection and the transmission of the HGV in the rhesus monkey provide an appropriate animal model for the study of HGV.
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Objective To review the current situation and developments of researches into important pathogenic microorganisms domestically and abroad,and to suggest the orientation of research work and development in pathogenic microbiology in PLA.Methods The achievements and advances of research work achieved domestically and abroad in the past five years regarding important viruses(such as hepatitis viruses,human immunodeficiency virus,influenza virus,encephalitis viruses and hantaanvirus)and bacteria (such as Mycobacterium tuberculosis,Streptococcus suis serotype 2,Yersinia pestis,Bacillus anthracis and Helicobacterp ylori)were retrieved and reviewed using intelligence research methods.Results Infectious diseases caused by pathogenic microorganisms were the most severe hazards to health and life of human beings.Especially in the past thirty years,newly emerging infectious diseases and recurrence of previonsly controlled infectious diseases had received wide attention.Infectious diseases control had been greatly improved owing to the increasing discoveries in the knowledge about pathogenic microorganisms.Conclusions During the period of "Twelfth Five-Years Plan" ,a big team of science and technology personnel with strong innovative ability in the domain of medical microbiology should be brought up in PLA;and a number of advanced and consummate research bases and technology platforms should be built up;to apply for and realize a batch of major research projects,strive to make a number of scientific achievements with innovation and important application prospects,improve the transformation efficiency of scientific and technological achievements and contribution of scientific and technological progress,and strive to achieve important progresses and breakthrough in mainstream research.
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Objective: To study the prevalence and pathogenesis of TT virus (TTV) in hemodialysis patients. Methods: Serum TTV DNA was tested in 69 hemodialysis patients from our hospital by nested-PCR using primers from a conservative region of TTV genenome, genetic analysis and detection of hepatitis C virus antibody (anti-HCV) and the levels of alanine aminotransferase (ALT) were also carried out simultaneously. Results: The overall prevalence of TTV viremia was 27.5%. The PCR-amplified gene fragment from one patient was sequenced, and its gene sequence homologies with GH1,TA278, TTVCHN1 and TTVCHN2 ranged from 89% to 100%, its deduced amino acid sequence ranged from 87% to 100%. There was no significant difference of TTV prevalence between anti-HCV positive and negative patients. No significant elevation of ALT was found in all patients. Conclusion: High prevalence of TTV infection is found among hemodialysis patients, and TTV infection has no significant association with HCV infection or elevation of ALT.
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Hepatitis C virus cell entry is mediated by multiple factors,including various receptors and cellular factors that trigger virus uptake by the hepatocyte.Occludin is a newly identified essential co-receptor for HCV entry together with CD81,SR-B1 and CLDN1.CLDN1 and occludin highlight the importance of studying the effects of tight junction and cell polarization on HCV entry.Study on cell polarization and tight junction can help to discover new targets for HCV therapy,and therefore interfere the cell entry and cell-cell spread of HCV.This review summarizes the current knowledge of hepatocyte polarization,tight junction and its major integral proteins CLDN1 and occludin,polarized cell culture system and its relation with HCV entry.
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Aim Vascular endothelial cell growth inhibitor(VEGI) is a recently discovered novel member of the TNF superfamily,which is expressed predominantly in endothelial cells.As an endothelial cell-specific negative regulator of angiogenesis,the relationship between structure and function of VEGI is not understood at present.Methods In order to explore the functional key amino acids of VEGI,four mutants of VEGI(E45→R,G47→A,Y111→F,Y111→T) were construced by site-directed mutagenesis,and recombinant proteins were generated from E.coli.Four mutant proteins behaved similar to the wild type VEGI in various physico-chemical assays.The proliferation of HUVEC and chick choriallantic membrane assay were performed to study the activity of four mutants.Results The mutant E45→R significantly decreased the biological activity,and the mutant G47→A caused a slight drop on activity,but the mutants Y111→F,Y111→T almost completely abolished biological activity.Conclusion It suggests that Y111 is an important residue in biological activity,which may play a direct role in receptor recognition.Moreover,the tyrosine ring and hydroxy group of the amino acid are important determinant of biological activity.Additionally,E45 also plays an important role in biological activity of VEGI.
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The severe acute respiratory syndrome (SARS) has been spreading in nearly 30 countries and regions worldwide recently. In response to its outbreak, many laboratories worldwide collaborated to identify the causative agent of SARS. A new type of coronavirus(named SARS CoV)has been isolated consequently, and the complete genomic sequences of the SARS CoV have been published. It is very important, at this stage, to deeply investigate the functional genome of SARS CoV with modern molecular techniques. As a new gene silencing method at RNA level, the recently established RNA interference will be a useful approach for the studies of SARS CoV genome.
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Hepatitis C virus (HCV) is a major causative agent for sporadic and post-transfusion hepatitis, which frequently progresses into chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. In order to clarify the genomic variations and the structural characteristics of Chinese HCV isolate, we extracted HCV genomic RNA from plasma specimens of Chinese hepatitis C (HC) patients, reverse-transcribed to HCV cDNA with random primers and constructed successfully an HCV cDNA R gt11 library of Chinese type. Two positive clones (Q349 and Q653) were selected by immunoscreening from the library and subcloned into plasmid vector pUC18. Sequence analyses indicated that Q349 was derived from core region (positions 554-902) of HCV genome while Q653 was from NS3 region (positions 4175-4827) corresponding with the prototype HCV nucleotide sequence. The homologies of Q349 and Q653 with the equivalent sequences of HCV prototype were 86.8% and 80.2% at the nucleotide level, and 97.3% and 93.1% at the amino acid level, respectively. It was found that Chinese HCV clones had higher homologies with Japanese HCV isolates, and should belong to HCV group II. Specificity test proved that the encoded peptides of the 2 Chinese HCV cDNA clones reacted specifically with sera from HC patients and had no reaction with sera from healthy individuals. More importantly, clone Q653 showed higher positive reaction rates with Chinese HC sera (95.8%) than those with Japanese ones (85.7%), which strongly suggests that the sequences from Chinese HCV genome (especially from NS regions) would be more suitable for primer designing or peptide synthesis for the use in the detection of HCV infection among Chinese people.