Publications by authors named "Xiaolin Ji"

22 Publications

  • Page 1 of 1

SPP1 overexpression is associated with poor outcomes in ALK fusion lung cancer patients without receiving targeted therapy.

Sci Rep 2021 Jul 7;11(1):14031. Epub 2021 Jul 7.

Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Haidian District, Beijing, 100191, People's Republic of China.

The screening of non-small cell lung cancer (NSCLC) tumors for anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is important because of the dramatically favorable therapy response to ALK inhibitor. However, the exact mechanism of poor survival in ALK fusion lung cancer patients without receiving targeted therapy is unclear. In this study, total of 521 tumor specimens from Chinese patients with lung cancer were screened for ALK fusion by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH). As results, there were no cases of coexisting EGFR and ALK mutations identified. Fourteen cases (2.7%) harbored ALK fusion, including eight solid adenocarcinomas with signet ring cell features, four acinar adenocarcinomas with cribriform pattern containing mucin, one adenosquamous carcinoma and one micropapillary adenocarcinoma with mucin. Six (42.9%) of fourteen patients with ALK-positive lung cancer had stage IV disease, and five ALK-positive patients treated with platinum-based chemotherapy had poor outcome (all patients were dead and the mean survival time was 12 months), compared to 72 months for patients with ALK inhibitor therapy. Furthermore, Five ALK-positive cases were analyzed by whole exome sequencing (WES) and via direct transcript counting using a digital probe-base (NanoString) to explore the driver genes. Deregulation of PI3K/AKT signaling pathway in ALK-positive lung cancer was demonstrated by WES analysis, and significantly increased mRNA of ALK, ROS1, MET, SPP1 and PI3K signaling pathway was identified by NanoString assay. The concordance between NanoString, IHC and FISH methodologies for detecting ALK fusion was 100%. Significant overexpression of SPP1 protein in ALK-positive lung cancer was confirmed by IHC compared to paired adjacent normal tissues and ALK-negative cancers. Thus we concluded that SPP1 overexpression is associated with poor outcomes for patients with ALK fusion lung cancer without receiving targeted therapy and PI3K/AKT/SPP1 pathway may become the promising targets in patients with aggressive lung cancer.
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http://dx.doi.org/10.1038/s41598-021-93484-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263595PMC
July 2021

Suprascapular nerve block is a clinically attractive alternative to interscalene nerve block during arthroscopic shoulder surgery: a meta-analysis of randomized controlled trials.

J Orthop Surg Res 2021 Jun 11;16(1):376. Epub 2021 Jun 11.

Department of Orthopedic, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Dongxiaokou Town, Changping District, Beijing, 102218, China.

Background: The interscalene brachial plexus block (ISB) is a commonly used nerve block technique for postoperative analgesia in patients undergoing shoulder arthroscopy surgery; however, it is associated with potentially serious complications. The use of suprascapular nerve block (SSNB) has been described as an alternative strategy with fewer reported side effects for shoulder arthroscopy. This review aimed to compare the impact of SSNB and ISB during shoulder arthroscopy surgery.

Methods: A meta-analysis was conducted to identify relevant randomized controlled trials involving SSNB and ISB during shoulder arthroscopy surgery. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through March 2021.

Results: We identified 1255 patients assessed in 17 randomized controlled trials. Compared with the ISB group, the SSNB group had higher VAS at rest in PACU (P = 0.003), 1 h after operation (P = 0.005), similar pain score 2 h (P = 0.39), 3-4 h (P = 0.32), 6-8 h after operation (P = 0.05), then lower VAS 12 h after operation (P = 0.00006), and again similar VAS 1 day (P = 0.62) and 2 days after operation (P = 0.70). As for the VAS with movement, the SSNB group had higher pain score in PACU (P = 0.03), similar VAS 4-6 h after operation (P = 0.25), then lower pain score 8-12 h after operation (P = 0.01) and again similar VAS 1 day after operation (P = 0.3) compared with the ISB group. No significant difference was found for oral morphine equivalents use at 24 h (P = 0.35), duration of PACU stay (P = 0.65), the rate of patient satisfaction (P = 0.14) as well as the rate of vomiting (P = 0.56), and local tenderness (P = 0.87). However, the SSNB group had lower rate of block-related complications such as Horner syndrome (P < 0.0001), numb (P = 0.002), dyspnea (P = 0.04), and hoarseness (P = 0.04).

Conclusion: Our high-level evidence established SSNB as an effective and safe analgesic technique and a clinically attractive alternative to interscalene block with the SSNB'S advantage of similar pain control, morphine use, and less nerve block-related complications during arthroscopic shoulder surgery, especially for severe chronic obstructive pulmonary disease, obstructive sleep apnea, and morbid obesity. Given our meta-analysis's relevant possible biases, we required more adequately powered and better-designed RCT studies with long-term follow-up to reach a firmer conclusion.
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http://dx.doi.org/10.1186/s13018-021-02515-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194158PMC
June 2021

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

J Hepatol 2021 08 24;75(2):439-441. Epub 2021 Apr 24.

CHESS-COVID-19 Group, The Third People's Hospital of Zhenjiang City, Zhenjiang, China.

Background & Aims: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD.

Methods: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination.

Results: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m (IQR 23.8-28.1 kg/m). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained.

Conclusions: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD.

Lay Summary: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.
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http://dx.doi.org/10.1016/j.jhep.2021.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185617PMC
August 2021

Preoperative Functional Platelet Number Is Inversely Associated With 30-Day Mortality After Cardiac Surgery: A Retrospective Cohort Study.

Semin Cardiothorac Vasc Anesth 2020 Dec 23;24(4):313-320. Epub 2020 Jul 23.

University of Louisville, Louisville, KY, USA.

. We hypothesize that preoperative functional platelet number (platelet count multiplied by platelet aggregation percentage) are associated with 30-day mortality after cardiac surgery. . We linked our preoperative testing database with the STS (Society of Thoracic Surgeon) database to form a study cohort of 1390 patients who had cardiac surgeries between January 2008 and December 2013. Preoperative tests of platelet count and platelet aggregation were routinely performed on all cardiac surgical patients within 24 hours before entering the operating room. Multiple logistic regression models were used to determine whether functional platelet number are associated with 30-day mortality, modified composite major adverse cardiocerebral events, postoperative renal failure or requirement for new renal replacement therapy, and reoperation for bleeding. Log-linear models were used to examine whether functional platelet numbers are associated with hospital length of stay and intensive care unit length of stay. . Functional platelet number had an inverse association with 30-day mortality, and each 50 × 10/L increase in functional platelet number resulted in decreased 30-day mortality (odds ratio of 0.767 with 95% confidence interval = 0.591-0.996). For secondary outcomes, functional platelet number was neither associated with major adverse cardiocerebral event nor length of stay. However, we found that each 50 × 10/L increase in functional platelet number was associated with decreased reoperations for bleeding (odds ratio of 0.778 with 95% confidence interval = 0.636-0.951). . The preoperative functional platelet number had significant associations with 30-day mortality after cardiac surgery. Functional platelet number could be used to guide timing of cardiac surgery, especially as more and more patients are receiving antiplatelet medications nowadays.
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http://dx.doi.org/10.1177/1089253220943023DOI Listing
December 2020

Premature Stop Codon at Residue 101 within HIV-1 Rev Does Not Influence Viral Replication of Clade BC but Severely Reduces Viral Fitness of Clade B.

Virol Sin 2020 Apr 11;35(2):181-190. Epub 2019 Dec 11.

State Key Laboratory of Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.

HIV-1 Rev is an accessory protein that plays a key role in nuclear exportation, stabilization, and translation of the viral mRNAs. Rev of HIV-1 clade BC often shows a truncation of 16 AAs due to a premature stop codon at residue 101. This stop codon presents the highest frequency in clade BC and the lowest frequency in clade B. In order to discover the potential biological effect of this truncation on Rev activity and virus replication of clade BC, we constructed Rev expression vectors of clade BC with or without 16 AAs within C-terminal separately, and replaced the stop codon by Q in a CRF07_BC infectious clone. We found that 16 AAs truncation had no effect on expression and activity of Rev in clade BC. Also, the mutation from the stop codon to Q had no effect on virus replication of clade BC. Next, to investigate the effect of this truncation on Rev activity and replication capacity of clade B, Rev expression vectors of clade B carrying or lacking 16 AAs in C-terminal were constructed respectively, and residue Q at position 101 within Rev was substituted by the stop codon in a clade B infectious clone. It was found that 16 AAs truncation significantly down-regulated Rev expression and impaired clade B Rev activity. Furthermore, a Q-to-stop codon substitution within Rev significantly reduced viral replication fitness of clade B. These results indicate that the premature stop codon at residue 101 within Rev exerts diverse impact on viral replication among different HIV-1 clades.
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http://dx.doi.org/10.1007/s12250-019-00179-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198662PMC
April 2020

CTL-mediated immunotherapy can suppress SHIV rebound in ART-free macaques.

Nat Commun 2019 05 21;10(1):2257. Epub 2019 May 21.

Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

A major barrier to human immunodeficiency virus (HIV) cure is the existence of viral reservoirs that lead to viral rebound following discontinuation of antiretroviral therapy (ART). We postulate that enhancing cytotoxic T lymphocytes (CTL) targeting conserved envelope (Env) regions can eliminate HIV infected cells in latency. Here, we evaluate the use of adoptively transferred HIV vaccine-induced subtype C Env-specific CTLs in a macaque subtype B simian-human immunodeficiency virus (SHIV) model to determine whether plasma viremia can be controlled after ART interruption. We demonstrate that adoptive cellular therapy (ACT) using autologous Env-specific T cells augmented by therapeutic vaccination can suppress ART-free viral rebound in the SHIV model. Furthermore, phenotypic and functional characterization of adoptively transferred cells in ACT-responsive and nonresponsive animals support a critical role for cross-reactive central memory T cells in viremia control. Our study offers an approach to potentiate immunological suppression of HIV in the absence of antiviral drugs.
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http://dx.doi.org/10.1038/s41467-019-09725-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529452PMC
May 2019

[Research advance in chondrogenic differentiation of adipose-derived stem cells].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Feb;44(2):201-208

Department of Pathophysiology, Central South University, Changsha 410078, China.

Articular cartilage lesions due to injury or other pathology are often difficult to heal, and the outcomes of the clinical treatment widely used today are far from satisfaction. Adipose-derived stem cells (ADSCs) are multipotent stem cells from adipose tissue. Tissue engineering based on the ability of ADSCs to differentiate into chondrocytes provides a new idea for the repair and regeneration of articular cartilage defects. The method for inducing the differentiation of ADSCs into chondrocytes in vitro who have been quite well established, which mainly include the use of growth factors and scaffolds to mimic the in vivo microenvironment, thereby promoting the differentiation of ADSCs into chondrocytes.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.022.013DOI Listing
February 2019

Early Env-specific CTLs effectively suppress viral replication in SHIV controller macaques.

Cell Immunol 2018 09 5;331:30-37. Epub 2018 May 5.

Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Haidian District, Beijing 100191, China; State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China. Electronic address:

Early immunological events in acute HIV infection are thought to fundamentally influence long-term disease outcomes. Though the contribution of Gag-specific CD8 T cell responses to early viral control is well established, little is known about the role of Env-specific CD8 T cell responses in controlling viral replication during acute infection. In a macaque simian-human immunodeficiency virus (SHIV) model, some macaques who were able to control SHIV replication after ART interruption showed expansion of Env-specific CD8 T cell responses during acute infection, compared to macaques who progressed to viral rebound. To better understand the function of early Env-specific CD8 T cells, we isolated, expanded and examined their ability to act as effectors in vitro. We observed that Env-specific CD8 T cell clones have the capacity to directly recognize and kill SHIV-infected CD4 T cells, but failed to reduce viral replication in SHIV-infected macrophages. Our data suggest that early Env-specific CD8 T cell responses during acute SHIV infection contribute substantially to the control of viral replication. The T-cell clones composing of Env-specific effector cells demonstrates in vitro phenotypic and functional characteristics with the potentials to provide longlasting clinical benefit of in vivo HIV study.
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http://dx.doi.org/10.1016/j.cellimm.2018.05.001DOI Listing
September 2018

Identification of suh gene and evidence for involvement of notch signaling pathway on gonadal differentiation of Yellow River carp (Cyprinus carpio).

Fish Physiol Biochem 2018 Feb 21;44(1):375-386. Epub 2017 Nov 21.

College of Life Science, Henan Normal University, 46# East of Construction Road, Xinxiang, Henan, 453007, People's Republic of China.

The suh gene is crucial in Notch pathway and regulates mammalian gonad development. In this study, the sequences of suh1 and suh2 genes in Yellow River carp (Cyprinus carpio) were verified. The partial 5'-flanking regions of suh1 and suh2 were analyzed and several potential transcription factor-binding sites were identified. Phylogenetic, gene structure, and chromosome synteny analyses revealed that carp suh1 and suh2 were orthologs and homologous to vertebrate suh. Investigation of the expression profiles of suh1 and suh2 with qPCR showed that these genes were abundant in the brain and gonad of carp, with suh1 exhibiting sexual dimorphism expression pattern in gonad. To study the relationship between gonad differentiation and Notch signaling, primordial gonads were exposed to DAPT, an inhibitor of Notch signaling, in vitro and in vivo. The results revealed a significant downregulation of suh1 and other Notch genes in vitro. In addition, expression of male-biased genes, such as amh, dmrt1, etc., was downregulated, whereas that of female-biased genes, such as foxl2, gdf9, etc., was upregulated. When the primordial gonads were subjected to long-term DAPT exposure, an increased proportion of ovary and delay in testis development were observed. These results suggest that suh gene may have a conservative function between teleosts and mammals. Furthermore, Notch signaling was found to be involved in gonad differentiation in Yellow River carp, and DAPT was noted to inhibit and enhance the expression of male- and female-biased genes, respectively, and induce the increase in number of females.
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http://dx.doi.org/10.1007/s10695-017-0441-5DOI Listing
February 2018

Transcriptome analysis of three critical periods of ovarian development in Yellow River carp (Cyprinus carpio).

Theriogenology 2018 Jan 9;105:15-26. Epub 2017 Sep 9.

College of Life Science, Henan Normal University, Xinxiang, Henan 453007, People's Republic of China. Electronic address:

Ovary development is a complex process involving numerous genes; the molecular mechanism underlying the ovary development of carp is still unknown. Here we used Illumina HiSeq™ 2500 to explore the transcriptome of undifferentiated gland (PG), juvenile ovary (OJ) and adult ovary (OA) of Yellow River carp (Cyprinus carpio). A total of 58,749 unigenes were obtained, comprising 45,707 known genes and 13,042 new genes. We identified differentially-expressed genes (DEGs) during development and characterized the functional properties of DEGs by comparison with the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes databases. qRT-PCR was used to analyze the expression of 22 DEGs and the results corresponded with those of RNA-Seq. Among DEGs between PG and OJ, some upstream regulators of gonad development were upregulated in PG, such as cyp19a and sox9, while some oocyte-specific genes were upregulated in OJ, such as nobox, bmp15 and zp2. Among DEGs between OJ and OA, many oocyte physiological function-related genes were upregulated in OA, such as fem-1 and foxl2. GO analysis showed a higher number of DEGs from PG-OJ analysis were assigned to reproduction terms. Furthermore, our investigation has also revealed DEGs identified from PG-OJ analysis were enriched in several important functional pathways, such as Fanconi anemia and the notch signal pathway. These data suggested a dynamic shift in gene expression during ovary development, and DEGs between PG and OJ provided crucial candidate gene data for the study of ovarian differentiation. Additionally, a total of 1,776,769 single nucleotide polymorphisms and 157,279 INDEs were revealed from transcriptome data. This result will contribute to knowledge of ovary differentiation of Yellow River carp.
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http://dx.doi.org/10.1016/j.theriogenology.2017.08.027DOI Listing
January 2018

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction.

Oncotarget 2017 Aug 3;8(34):55901-55914. Epub 2017 Jun 3.

Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. Using microarray analyses, we comprehensively compared long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) expression profiles in hippocampal tissues from a mouse model of POCD and control mice. A total of 175 lncRNAs, 117 mRNAs, and 26 miRNAs were differentially expressed between POCD and control mice. Gene ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of dysregulated genes. Correlated coding-noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) expression networks were constructed using bioinformatics methods. lncRNA NONMMUT000708 correlated positively with expression of the inflammation-related gene . lncRNAs NONMMUT043249 and NONMMUT028705 mediated gene expression by binding the transcription factor cAMP response element-binding protein (CREB). The constructed ceRNA network suggested lncRNA NONMMUT055714 binds competitively with miR-7684-5p, increasing expression of its target gene, . Finally, eight dysregulated lncRNAs, four miRNAs, and ten mRNAs were confirmed quantitative real-time polymerase chain reaction (PCR) in 10 POCD-healthy mouse paired samples. These results suggest that lncRNAs and miRNAs are involved in POCD pathogenesis and progression. Our ceRNA network will improve understanding of lncRNA-mediated ceRNA regulatory mechanisms operating during the pathogenesis of POCD.
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http://dx.doi.org/10.18632/oncotarget.18362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593532PMC
August 2017

Prone positioning for intramedullary nailing of subtrochanteric fractrures, the techniques of intraoperative fluoroscopy and reduction: A technique note.

Injury 2017 Oct 18;48(10):2354-2359. Epub 2017 Aug 18.

Orthopaedic Department of Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China. Electronic address:

The treatment of subtrochanteric fractures is a challenge for orthopaedic trauma surgeons. Three positions have been described previously: supine on a fracture table, supine on a flat radiolucent table, and the lateral decubitus position on a flat radiolucent table. Each one has its advantages and limitations. In this article we describe a prone position for intramedullary nailing of subtrochanteric femoral fractures. This position has the advantages including: 1) an easy approach to reduce and maintain the reduction of fracture by adjusting only the leg plate on injured side, 2) perfect intraoperation fluoroscopic imaging on both anteroposterior view and lateral view, and 3) an easy approach to establish an appropriate entry point even in obese patients.
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http://dx.doi.org/10.1016/j.injury.2017.08.025DOI Listing
October 2017

Drug resistance-related mutations T369V/I in the connection subdomain of HIV-1 reverse transcriptase severely impair viral fitness.

Virus Res 2017 04 6;233:8-16. Epub 2017 Mar 6.

State Key Laboratory of Infectious Diseases Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of infectious Diseases, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China; Division of Research of Virology and Immunology, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Changping District, Beijing 102206, China. Electronic address:

Fitness is a key parameter in the measurement of transmission capacity of individual drug-resistant HIV. Drug-resistance related mutations (DRMs) T369V/I and A371V in the connection subdomain (CN) of reverse transcriptase (RT) occur at higher frequencies in the individuals experiencing antiretroviral therapy failure. Here, we evaluated the effects of T369V/I and A371V on viral fitness, in the presence or in the absence of thymidine analogue resistance-associated mutations (TAMs) and assessed the effect of potential RT structure-related mechanism on change in viral fitness. Mutations T369V/I, A371V, alone or in combination with TAMs were introduced into a modified HIV-1 infectious clone AT1 by site-directed mutagenesis. Then, experiments on mutant and wild-type virus AT2 were performed separately using a growth-competition assay, and then the relative fitness was calculated. Structural analysis of RT was conducted using Pymol software. Results showed that T369V/I severely impaired the relative virus fitness, and A371V compensated for the viral fitness reduction caused by TAMs. Structural modeling of RT suggests that T369V/I substitutions disrupt powerful hydrogen bonds formed by T369 and V365 in p51 and p66. This study indicates that the secondary DRMs within CN might efficiently damage viral fitness, and provides valuable information for clinical surveillance and prevention of HIV-1 strains carrying these DRMs.
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http://dx.doi.org/10.1016/j.virusres.2017.03.002DOI Listing
April 2017

Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor.

Immunity 2016 Apr 5;44(4):939-50. Epub 2016 Apr 5.

State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China; Health Science Center, Peking University, Haidian District, Beijing 100191, China; School of Medicine, Nankai University, Nankai District, Tianjin 300071, China. Electronic address:

VRC01-class antibodies neutralize diverse HIV-1 strains by targeting the conserved CD4-binding site. Despite extensive investigations, crucial events in the early stage of VRC01 development remain elusive. We demonstrated how VRC01-class antibodies emerged in a Chinese donor by antigen-specific single B cell sorting, structural and functional studies, and longitudinal antibody and virus repertoire analyses. A monoclonal antibody DRVIA7 with modest neutralizing breadth was isolated that displayed a subset of VRC01 signatures. X-ray and EM structures revealed a VRC01-like angle of approach, but less favorable interactions between the DRVIA7 light-chain CDR1 and the N terminus with N276 and V5 glycans of gp120. Although the DRVIA7 lineage was unable to acquire broad neutralization, longitudinal analysis revealed a repertoire-encoded VRC01 light-chain CDR3 signature and VRC01-like neutralizing heavy-chain precursors that rapidly matured within 2 years. Thus, light chain accommodation of the glycan shield should be taken into account in vaccine design targeting this conserved site of vulnerability.
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http://dx.doi.org/10.1016/j.immuni.2016.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862659PMC
April 2016

Interleukin-21 administration leads to enhanced antigen-specific T cell responses and natural killer cells in HIV-1 vaccinated mice.

Cell Immunol 2016 05 1;303:55-65. Epub 2016 Apr 1.

State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Changping District, Beijing 102206, China. Electronic address:

Interleukin-21 (IL-21), which belongs to IL-2 γ chain receptor cytokine family, is as an important regulator of immune responses. In this study, we developed a novel strategy for immunizing mice with a DNA/vaccinia/protein vaccine in the presence or absence of mouse IL-21 (mIL-21) to evaluate whether mIL-21 could enhance immune responses. Our results demonstrated that co-immunization with mIL-21 did not increase significantly the capacity of vaccine induced antibodies to bind to HIV-1 GP140. An effect of mIL-21 in adjusting the efficacy of HIV-1 vaccine through enhancing Th1 type immune response was however observed. The frequencies of HIV-1-specific cytokine-producing CD4+ T and CD4+ TEM cells, especially multifunctional T cell responses, were significantly increased by co-administrating with mIL-21. A significant increase was also observed in the frequency of NK cells in mIL-21 adjuvant groups. Taken together, combination of mIL-21 with HIV-1 vaccines led to distinct enhancement of NK cells and T cell immune responses associated with immune protection.
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http://dx.doi.org/10.1016/j.cellimm.2016.03.006DOI Listing
May 2016

Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes.

FEBS Lett 2015 Dec 22;589(24 Pt B):3938-44. Epub 2015 Nov 22.

Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China. Electronic address:

It has been reported that cystatin c (Cys C) closely correlates with metabolic disorders such as obesity and diabetes. However, it is still unknown whether Cys C plays a role for these disorders. Our results showed that the insulin signal transduction was largely impaired by Cys C in hepatocytes. In myotubes, however, the insulin signal transduction was not affected. Following experiments revealed that Cys C could induce endoplasmic reticulum stress (ER stress) in hepatocytes, whereas Cys C had no such an effect in myotubes. The alleviation of ER stress by 4-Phenyl butyric acid (4-PBA) restored the impaired insulin signal transduction in Cys C-treated hepatocytes. These results provided direct evidence that, by inducing ER stress, Cys C impairs insulin signal transduction in hepatocytes.
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http://dx.doi.org/10.1016/j.febslet.2015.11.029DOI Listing
December 2015

A recombinant avian leukosis virus subgroup j for directly monitoring viral infection and the selection of neutralizing antibodies.

PLoS One 2014 18;9(12):e115422. Epub 2014 Dec 18.

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China.

Avian leukosis virus subgroup J (ALV-J) has induced serious clinical outbreaks and has become a serious infectious disease of chickens in China. We describe here the creation of a recombinant ALV-J tagged with the enhanced green fluorescent protein (named rHPRS-103EGFP). We successfully utilize the rHPRS-103EGFP to visualize viral infection and for development of a simplified serum-neutralization test.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115422PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270768PMC
December 2015

Expression of neddylation-related proteins in melanoma cell lines and the effect of neddylation on melanoma proliferation.

Oncol Lett 2014 May 7;7(5):1645-1650. Epub 2014 Mar 7.

Department of Surgical Urology, Affiliated Xingtai People's Hospital of Hebei Medical University, Xingtai, Hebei 054001, P.R. China.

Neddylation promotes the process of ubiquitination, which plays a critical role in the degradation of numerous proteins, including cell cycle and apoptosis regulators. In our previous study, an increase in neddylation was identified in melanoma cell lines. In the present study, the upregulation of neddylation was detected in melanoma tissues which confirmed the results of our previous study on melanoma cell lines. To explore the mechanism by which the process of neddylation was increased, the enzymes that regulate the process were investigated. These neddylation-related regulatory enzymes are potential targets for melanoma therapy. Downregulation of UBA3, a subunit of the E1 enzyme, by RNA interference caused cell cycle arrest at G0G1 in the M14 cell line. In addition, cyclin D expression declined, whereas p27, p21 and bax expression increased. These findings suggest that interfering with the neddylation pathway may decrease the proliferation of melanoma through the modulation of cell cycle regulators and apoptosis promoters.
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http://dx.doi.org/10.3892/ol.2014.1953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997721PMC
May 2014

A 19-nucleotide insertion in the leader sequence of avian leukosis virus subgroup J contributes to its replication in vitro but is not related to its pathogenicity in vivo.

PLoS One 2014 20;9(1):e84797. Epub 2014 Jan 20.

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.

Subgroup J avian leukosis virus (ALV-J) was first isolated from meat-type chickens that had developed myeloid leukosis and since 2008, ALV-J infections in chickens have become widespread in China. A comparison of the sequence of ALV-J epidemic isolates with HPRS-103, the ALV-J prototype virus, revealed several distinct features, one of which is a 19-nucleotide (nt) insertion in the leader sequence. To determine the role of the 19-nt insertion in ALV-J pathogenicity, a pair of viruses were constructed and rescued. The first virus was an ALV-J Chinese isolate (designated rSD1009) containing the 19-nt insertion in its leader sequence. The second virus was a clone, in which the leader sequence had a deleted 19-nt sequence (designated rSD1009△19). Compared with rSD1009△19, rSD1009 displayed a moderate growth advantage in vitro. However, no differences were demonstrated in either viral replication or oncogenicity between the two rescued viruses in chickens. These results indicated that the 19-nt insertion contributed to ALV-J replication in vitro but was not related to its pathogenicity in vivo.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084797PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896346PMC
December 2014

Overexpression of microRNA gga-miR-1650 decreases the replication of avian leukosis virus subgroup J in infected cells.

J Gen Virol 2013 Oct 1;94(Pt 10):2287-2296. Epub 2013 Aug 1.

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.

MicroRNAs (miRNAs) are a class of small regulatory non-coding RNAs that modulate gene expression at the post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have demonstrated that a number of cellular miRNAs play a role during viral infection. In this study, a luciferase-reporter system carrying the 5' untranslated region (5' UTR) and 3' UTR of avian leukosis virus subgroup J (ALV-J) was used to determine whether cellular miRNAs are involved in ALV-J infection. The miRNA gga-miR-1650 was screened for its potential interaction with the 5' UTR of ALV-J and the ability to suppress luciferase-reporter activity. A mutational analysis of predicted gga-miR-1650-binding sites showed that the 5' and 3' ends of gga-miR-1650 contributed to the interaction between gga-miR-1650 and its target located at the 5' UTR. Overexpression of miRNA gga-miR-1650 was shown to downregulate the expression of the Gag protein and influence the replication of ALV-J through binding to the 5' UTR. Overall, this report provides the basis for the development of new strategies for anti-ALV-J intervention.
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http://dx.doi.org/10.1099/vir.0.054007-0DOI Listing
October 2013

Development of a new duplex real-time polymerase chain reaction assay for detection of dicer in G. gallus.

J Microbiol Biotechnol 2013 May;23(5):630-6

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

Recently, there has been a growing body of evidence showing that cellular microRNAs (miRNAs) are involved in virus-host interactions. Numerous studies have focused on analyses of the expression profiles of cellular miRNAs, but the expression patterns of Dicer, which is responsible for the generation of miRNAs, have only rarely been explored in Gallus gallus. We developed a duplex realtime reverse transcriptase polymerase chain reaction (RTPCR) assay for the relative quantification of the mRNAs of Dicer and beta-actin in G. gallus. To apply this method, the expression of Dicer in avian cells after infection with avian leukosis virus subgroup J (ALV-J) was detected using our established duplex real-time RT-PCR. The duplex realtime RT-PCR assay is sufficiently sensitive, specific, accurate, reproducible, and cost-effective for the detection of Dicer in G. gallus. Furthermore, this study, for the first time, demonstrated that ALV-J can induce differential expression of Dicer mRNA in the ALV-J-infected cells.
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http://dx.doi.org/10.4014/jmb.1211.11083DOI Listing
May 2013

Differential expression of microRNAs in avian leukosis virus subgroup J-induced tumors.

Vet Microbiol 2013 Feb 26;162(1):232-8. Epub 2012 Oct 26.

Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

Avian leukosis virus subgroup J (ALV-J) has become pandemic and induced serious clinical outbreaks in chickens in China. In particular, ALV-J induced various clinical tumors in infected chickens, which caused enormous economic losses to poultry. In this study, an infectious clone from an epidemic ALV-J Chinese isolate designated HLJ09SH01 was constructed and rescued. The rescued virus (named rHLJ09SH01) was inoculated into specific-pathogen-free (SPF) layer chickens, and infected chickens were observed for 238 days to explore the oncogenicity of rHLJ09SH01. As a result, 57.9% of rHLJ09SH01-infected chickens produced tumors. Accumulating evidence shows that microRNAs (miRNAs) have a close relationship with tumorigenesis. To gain more insight into the tumorigenesis of ALV-J, a miRNA microarray was performed as part of an investigation of changes in host miRNA expression in a liver tumor from ALV-J infected chickens. The results showed that four miRNAs were significantly differentially expressed; these data were verified using real-time PCR. Bioinformatics analysis showed the differentially expressed miRNAs to be involved in some tumorigenesis-related signaling pathways, such as the MAPK signaling pathway and the Wnt signaling pathway, which may represent a possible signaling pathway that was involved in the ALV-J-induced tumorigenesis.
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http://dx.doi.org/10.1016/j.vetmic.2012.10.023DOI Listing
February 2013
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