Publications by authors named "Jinyu Xia"

22 Publications

  • Page 1 of 1

Tuberculosis Diagnosis by Metagenomic Next-generation Sequencing on Bronchoalveolar Lavage Fluid: a cross-sectional analysis.

Int J Infect Dis 2020 Dec 24;104:50-57. Epub 2020 Dec 24.

Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China. Electronic address:

Background: Metagenomic next-generation sequencing (mNGS) is an effective diagnostic method for infectious diseases, however, its clinical utility for tuberculosis (TB) diagnosis remains to be demonstrated.

Methods: A total of 322 bronchoalveolar lavage fluid (BALF) samples were collected from 311 suspected and confirmed pulmonary TB patients and tested by mNGS, acid-fast bacillus (AFB) smear by microscopy, Xpert® MTB/RIF (Xpert), mycobacterium culture and bacterial/fungal culture. Diagnostic performance of mNGS was compared with conventional methods for detection of Mycobacterium tuberculosis complex (MTBC) and other pathogens in BALF. Underlying factors associated with positive detection in pulmonary TB patients were investigated.

Results: mNGS, Xpert and culture presented a high proportion of complete matching for MTBC detection (244/322, 75.8%). In pulmonary TB patients pre-treatment the sensitivity of MTBC detection by mNGS, Xpert, culture and smear was 59.9% (85/142), 69.0% (98/142), 59.9% (85/142) and 24.6% (35/142), respectively, and 79.6% overall; MTBC was detected by mNGS in 33.2% (5/34) Xpert and culture negative samples. Positive MTBC detection by mNGS was affected by Vitamin D, erythrocyte sedimentation rate, TB initial treatment/retreatment, and cavity in chest imaging (χ = 37.42, P < 0.001), but not by prior anti-TB therapy within 3 months. mNGS was able to detect new potential pathogens in 8.7% (28/322) of samples.

Conclusions: Combining mNGS with conventional detection methods could increase the detection rate for MTBC. Additionally, mNGS could identify pathogens in a non-targeted approach for better diagnosis of coinfection.
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http://dx.doi.org/10.1016/j.ijid.2020.12.063DOI Listing
December 2020

Rapid Fulminant Progression and Mortality Secondary to Septicemia with Hepatitis B Virus Infection Following the Ingestion of Snakehead Fish in Mainland China: A Case Report.

Foodborne Pathog Dis 2020 Dec 25;17(12):743-749. Epub 2020 Sep 25.

Department of Infectious Diseases, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China.

is an important ubiquitous Gram-negative and freshwater bacterium detected in different reservoirs. It can cause invasive diseases in humans. Herein, we report the first case in Mainland China of a fulminant death of a 29-year-old man as a result of a new, unexpected association between septicemic and hepatitis B viral infection (HBV). Herein, the patient died from multiple organ failure 5 d postadmission after the ingestion of Snakehead Fish meal. The isolated bacterium was initially misidentified as using VITEK-2, while whole-genome sequencing (WGS) revealed that the isolate is . WGS revealed the occurrence of three antimicrobial genes of resistance: , , and ; besides, major virulence factors were detected. , multilocus sequence typing (MLST) showed that our 17FW001 belonged to a novel sequence type (ST557). A comparative genomic analysis of our isolate with nine selected species was done, which elucidated the pathogenicity of our . In conclusion, we reported for the first time the association between and HBV in Mainland China. We revealed that septicemic could result in severe adverse clinical outcomes that end up with unexpected fulminant death especially when it is accompanied with HBV and sheds light on the virulence of and the high rate of its misdiagnosis that requires to urgently consider screening of all cases of for HBV in the future. Besides, caution should be taken while dealing with snakeheads which act as a vector for .
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http://dx.doi.org/10.1089/fpd.2019.2780DOI Listing
December 2020

Association between Nonalcoholic Fatty Liver Disease and Bone Mineral Density in HIV-Infected Patients Receiving Long-term TDF-Based Antiretroviral Therapy.

Curr HIV Res 2021 ;19(1):40-46

Department of Infectious Diseases, the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.

Background: Tenofovir (TDF) has a detrimental effect on bone mineral density (BMD), while nonalcoholic fatty liver disease (NAFLD) is associated with a lower BMD.

Objective: To help understand the mutual effects of NAFLD and TDF on BMD, this study was designed to explore the potential association between NAFLD and BMD in HIV-infected patients receiving long-term TDF-based antiretroviral therapy (ART).

Methods: A total of 89 HIV-infected patients who received TDF-based ART for more than three years were enrolled in this cross-sectional study. We measured BMD using an ultrasonic bone density apparatus, and liver ultrasonography was performed to determine the severity of the fatty liver. The association of NAFLD with BMD was examined using multiple logistic regression analyses.

Results: Patients with NAFLD showed a worse BMD status than those without NAFLD. The incidence rates of osteopenia (42.86% versus 25.93%) and osteoporosis (17.14% versus 3.70%) were significantly higher in HIV-infected patients with NAFLD than in those without NAFLD. After multivariate adjustment, the odds ratio (OR) for patients with NAFLD exhibiting a worse BMD status compared with those without NAFLD was 4.49 (95% confidence interval [CI] 1.42, 14.15).

Conclusion: Based on our results, NAFLD was significantly associated with a worse BMD status, including osteopenia and osteoporosis, in HIV patients after receiving long-term TDF-based ART. Furthermore, we may want to avoid using TDF for ART in HIV-infected patients with NAFLD.
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http://dx.doi.org/10.2174/1570162X18999200917120449DOI Listing
January 2021

Risk factors for the COVID-19 severity and its correlation with viral shedding: A retrospective cohort study.

J Med Virol 2021 02 16;93(2):952-961. Epub 2020 Sep 16.

Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.

Coronavirus disease 2019 (COVID-19) have become a pandemic in the world. This study is aim to explore risk factors for COVID-19 severity in the early stage and the correlation between the viral shedding and COVID-19 severity. We included inpatient with laboratory confirmed COVID-19 who had been discharged by 9 March 2020. The medical record data and dynamic change of biochemical indicators in-hospital were compared between common and severe patients. Eighty patients were included in this study. Multivariable regression demonstrated increasing odds of severity associated with the duration of fever (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10-1.82, per day increase; P = .007), C-reactive protein (CRP) (OR, 1.26; 95% CI, 1.04-1.52; P = .02), and PO  < 80 mm Hg (28.07, 95% CI, 1.50-524.12; P = .026) on admission. We found severe acute respiratory syndrome coronavirus 2 viral RNA could be long-term presence in respiratory tract and fecal sample, up to 43 and 46 days, respectively. However, the duration of viral shedding have no correlation with the COVID-19 severity. The duration of fever, elevated CRP and PO  < 80 mm Hg on admission were associated with the COVID-19 severity in the early stage and there is no correlation between the viral shedding and COVID-19 severity.
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http://dx.doi.org/10.1002/jmv.26367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821149PMC
February 2021

Efficacy of chloroquine versus lopinavir/ritonavir in mild/general COVID-19 infection: a prospective, open-label, multicenter, randomized controlled clinical study.

Trials 2020 Jul 8;21(1):622. Epub 2020 Jul 8.

Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Background: The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment has yet been confirmed. The adage "old drug, new trick" in this context may suggest the important therapeutic potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals. Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir.

Methods/design: This is a prospective, open-label, randomized controlled, multicenter clinical study. The study consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-sided tests with a statistical significance level of 5%.

Discussion: This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity and is safe, it could be tested as a future COVID-19 treatment.

Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR2000029741 . Registered on 11 February 2020.
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http://dx.doi.org/10.1186/s13063-020-04478-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341476PMC
July 2020

Clinical Time Features and Chest Imaging of 85 Patients With COVID-19 in Zhuhai, China.

Front Med (Lausanne) 2020 8;7:209. Epub 2020 May 8.

Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

An outbreak of SARS-CoV-2 infections began in Wuhan, China, and quickly spread to the entire country. We sought to delineate the time features of clinical symptoms, virological conversion, and chest radiological abnormalities in individuals infected with this virus in Zhuhai, China. In this retrospective study, we assessed 85 confirmed cases of COVID-19 in the Fifth Hospital of Sun Yat-sen University, Zhuhai, from the 17th of January to the 11th of February 2020. Outcomes were followed up until the 24th of February 2020. The median age of the 85 patients with COVID-19 was 43 years (range, 1-80); 56.5% (48/85) were female. The median time from the last known contact to the first SARS-CoV-2 positive test result was 8 days (0-18). The time to throat swab negativity for SARS-CoV-2 ranged from 5 to 36 days after illness onset. Patients with abnormal chest imaging findings on admission were older than those with normal imaging findings (median age, 50 [3-80] vs. 37 [1-69], = 0.031). Among patients with lung changes on admission, the risk of lesions was 13.8 times greater in the left lower lobe than in the right middle lobe. Most lung lesions appeared within 2 weeks of onset (median 4-5 days). The overall rates of lesions in the right upper/middle/lower lobe and left upper/lower lobe were 47.1, 30.6, 62.4% as well as 49.4 and 63.5%, respectively. The incubation period of SARS-CoV-2 may be longer than 14 days; thus, medical surveillance after contact is required for longer than this. The predominant sites of lung lesions are both lower lungs, whereas the lowest risk region is the right middle lobe.
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http://dx.doi.org/10.3389/fmed.2020.00209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225607PMC
May 2020

Treating COVID-19 with Chloroquine.

J Mol Cell Biol 2020 05;12(4):322-325

Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

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http://dx.doi.org/10.1093/jmcb/mjaa014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232130PMC
May 2020

Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study.

J Infect 2020 07 11;81(1):e1-e5. Epub 2020 Mar 11.

Department of Infectious Diseases, the Fifth Affiliated Hospital, Sun Yat-sen University, 52 East Meihua Road, Zhuhai 519000, Guangdong Province, China. Electronic address:

Background: Corona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only.

Methods: In this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5-21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7).

Results: We analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients' nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p < 0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p < 0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p < 0·05).

Conclusion: In patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.
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http://dx.doi.org/10.1016/j.jinf.2020.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156152PMC
July 2020

IL-21 Expands HIV-1-Specific CD8 T Memory Stem Cells to Suppress HIV-1 Replication In Vitro.

J Immunol Res 2019 30;2019:1801560. Epub 2019 Apr 30.

Department of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.

Due to the existence of viral reservoirs, the rebound of human immunodeficiency virus type 1 (HIV-1) viremia can occur within weeks after discontinuing combined antiretroviral therapy. Immunotherapy could potentially be applied to eradicate reactivated HIV-1 in latently infected CD4 T lymphocytes. Although the existence of HIV-1-specific CD8 T memory stem cells (Ts) is well established, there are currently no reports regarding methods using CD8 Ts to treat HIV-1 infection. In this study, we quantified peripheral blood antigen-specific CD8 Ts and then expanded HIV-1-specific Ts that targeted optimal antigen epitopes (SL9, IL9, and TL9) in the presence of interleukin- (IL-) 21 or IL-15. The suppressive capacity of the expanded CD8 Ts on HIV-1 production was measured by assessing cell-associated viral RNA and performing viral outgrowth assays. We found that the number of unmutated TL9-specific CD8 Ts positively correlated with the abundance of CD4 T cells and that the expression of IFN- was higher in TL9-specific CD8 Ts than that in non-TL9-specific CD8 Ts. Moreover, the antiviral capacities of IL-21-stimulated CD8 Ts exceeded those of conventional CD8 memory T cells and IL-15-stimulated CD8 Ts. Thus, we demonstrated that IL-21 could efficiently expand HIV-1-specific CD8 Ts to suppress HIV-1 replication. Our study provides new insight into the function of IL-21 in the suppression of HIV-1 replication.
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http://dx.doi.org/10.1155/2019/1801560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515191PMC
December 2019

Development of an Infectious Cell Culture System for Hepatitis C Virus Genotype 6a Clinical Isolate Using a Novel Strategy and Its Sensitivity to Direct-Acting Antivirals.

Front Microbiol 2018 4;9:2950. Epub 2018 Dec 4.

Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Hepatitis C virus (HCV) is classified into seven major genotypes, and genotype 6 is commonly prevalent in Asia, thus reverse genetic system representing genotype 6 isolates in prevalence is required. Here, we developed an infectious clone for a Chinese HCV 6a isolate (CH6a) using a novel strategy. We determined CH6a consensus sequence from patient serum and assembled a CH6a full-length (CH6aFL) cDNA using overlapped PCR product-derived clones that shared the highest homology with the consensus. CH6aFL was non-infectious in hepatoma Huh7.5 cells. Next, we constructed recombinants containing Core-NS5A or 5'UTR-NS5A from CH6a and the remaining sequences from JFH1 (genotype 2a), and both were engineered with 7 mutations identified previously. However, they replicated inefficiently without virus spread in Huh7.5 cells. Addition of adaptive mutations from CH6a Core-NS2 recombinant, with JFH1 5'UTR and NS3-3'UTR, enhanced the viability of Core-NS5A recombinant and acquired replication-enhancing mutations. Combination of 22 mutations in CH6a recombinant with JFH1 5'UTR and 3'UTR (CH6aORF) enabled virus replication and recovered additional four mutations. Adding these four mutations, we generated two efficient recombinants containing 26 mutations (26m), CH6aORF_26m and CH6aFL_26m (designated "CH6acc"), releasing HCV of 10-10 focus-forming units (FFU)/ml in Huh7.5.1-VISI-mCherry and Huh7.5 cells. Seven newly identified mutations were important for HCV replication, assembly, and release. The CH6aORF_26m virus was inhibited in a dose- and genotype-dependent manner by direct-acting-antivirals targeting NS3/4A, NS5A, and NS5B. The CH6acc enriches the toolbox of HCV culture systems, and the strategy and mutations applied here will facilitate the culture development of other HCV isolates and related viruses.
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http://dx.doi.org/10.3389/fmicb.2018.02950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288186PMC
December 2018

Adaptive mutation F772S-enhanced p7-NS4A cooperation facilitates the assembly and release of hepatitis C virus and is associated with lipid droplet enlargement.

Emerg Microbes Infect 2018 Aug 8;7(1):143. Epub 2018 Aug 8.

Institute of Human Virology and Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 501180, China.

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis and liver cancer worldwide. Adaptive mutations play important roles in the development of the HCV replicon and its infectious clones. We and others have previously identified the p7 mutation F772S and the co-presence of NS4A mutations in infectious HCV full-length clones and chimeric recombinants. However, the underlying mechanism of F772S function remains incompletely understood. Here, we investigated the functional role of F772S using an efficient JFH1-based reporter virus with Core-NS2 from genotype 2a strain J6, and we designated J6-p7/JFH1-4A according to the strain origin of the p7 and NS4A sequences. We found that replacing JFH1-4A with J6-4A (wild-type or mutated NS4A) or genotype 2b J8-4A severely attenuated the viability of J6-p7/JFH1-4A. However, passage-recovered viruses that contained J6-p7 all acquired F772S. Introduction of F772S efficiently rescued the viral spread and infectivity titers of J6-p7/J6-4A, which reached the levels of the original J6-p7/JFH1-4A and led to a concomitant increase in RNA replication, assembly and release of viruses with J6-specific p7 and NS4A. These data suggest that an isolate-specific cooperation existed between p7 and NS4A. NS4A exchange- or substitution-mediated viral attenuation was attributed to the RNA sequence, and no p7-NS4A protein interaction was detected. Moreover, we found that F772S-enhanced p7-NS4A cooperation was associated with the enlargement of intracellular lipid droplets. This study therefore provides new insights into the mechanisms of adaptive mutations and facilitates studies on the HCV life cycle and virus-host interaction.
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http://dx.doi.org/10.1038/s41426-018-0140-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081454PMC
August 2018

Identification of nucleotides in the 5'UTR and amino acids substitutions that are essential for the infectivity of 5'UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1).

Virology 2018 05 15;518:253-263. Epub 2018 Mar 15.

Program in Pathobiology, Fifth Affiliated Hospital and Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China. Electronic address:

Genotype 1b strain Con1 represents an important reference in the study of hepatitis C virus (HCV). Here, we aimed to develop an advanced infectious Con1 recombinant. We found that previously identified mutations A1226G/F1464L/A1672S/Q1773H permitted culture adaption of Con1 Core-NS5A (C-5A) recombinant containing 5'UTR and NS5B-3'UTR from JFH1 (genotype 2a), thus acquired additional mutations L725H/F886L/D2415G. C-5A containing all seven mutations (C-5A_7m) replicated efficiently in Huh7.5 and Huh7.5.1 cells and had an increased infectivity in SEC14L2-expressing Huh7.5.1 cells. Incorporation of Con1 NS5B was deleterious to C-5A_7m, however Con1 5'UTR was permissive but attenuated the virus. Nucleotides G1, A4, and G35 primarily accounted for the viral attenuation without affecting RNA translation. C-5A_7m was inhibited dose-dependently by simeprevir and daclatasvir, and substitutions at A4, A29, A34, and G35 conferred resistance to miR-122 antagonism. The novel Con1 5'UTR-NS5A recombinant, adaptive mutations, and critical nucleotides described here will facilitate future studies of HCV culture systems and virus-host interaction.
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http://dx.doi.org/10.1016/j.virol.2018.03.001DOI Listing
May 2018

Moloney leukemia virus 10 (MOV10) inhibits the degradation of APOBEC3G through interference with the Vif-mediated ubiquitin-proteasome pathway.

Retrovirology 2017 Dec 19;14(1):56. Epub 2017 Dec 19.

Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Background: MOV10 protein has ATP-dependent 5'-3' RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin-proteasome system (UPS).

Results: We demonstrate that MOV10 counteracts Vif-mediated degradation of A3G by inhibiting the assembly of the Vif-CBF-β-Cullin 5-ElonginB-ElonginC complex. Through interference with UPS, MOV10 enhances the level of A3G in HIV-1-infected cells and virions, and synergistically inhibits the replication and infectivity of HIV-1. In addition, the DEAG-box of MOV10 is required for inhibition of Vif-mediated A3G degradation as the DEAG-box mutant significantly loses this ability.

Conclusions: Our results demonstrate a novel mechanism involved in the anti-HIV-1 function of MOV10. Given that both MOV10 and A3G belong to the interferon antiviral system, their synergistic inhibition of HIV-1 suggests that these proteins may play complicated roles in antiviral functions.
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http://dx.doi.org/10.1186/s12977-017-0382-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735797PMC
December 2017

Negative HBcAg in immunohistochemistry assay of liver biopsy is a predictive factor for the treatment of patients with nucleos(t)ide analogue therapy.

J Cell Mol Med 2018 03 29;22(3):1675-1683. Epub 2017 Nov 29.

Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University (SYSU), Zhuhai, Guangdong, China.

The hepatitis B core antigen (HBcAg) is an important target for antiviral response in chronic hepatitis B (CHB) patients. However, the correlation between HBcAg in the hepatocyte nucleus and nucleos(t)ide analogue (NA) therapeutic response is unclear. We sought to evaluate the role of HBcAg by analysing liver biopsies for viral response in NA-naïve hepatitis B e antigen (HBeAg) positive (+) CHB patients via immunohistochemistry (IHC). A total of 48 HBcAg-negative (-) patients and 48 HBcAg (+) patients with matching baseline characteristics were retrospectively analysed for up to 288 weeks. Virological response (VR) rates of patients in the HBcAg (-) group were significantly higher at week 48 and 96 than the HBcAg (+) group (77.1% versus 45.8% at week 48, respectively, P = 0.002 and 95.3% versus 83.3% at week 96, respectively, P = 0.045). The serological negative conversion rate of HBeAg was significantly higher in the HBcAg (-) than in the HBcAg (+) group from week 96 to 288 (35.4 % versus 14.6% at week 96, respectively, P = 0.018; 60.4% versus 14.6%, respectively, P < 0.001 at week 144; 72.9% versus 35.4%, respectively, P < 0.001 at week 288). The cumulative frequencies of VR and lack of HBeAg were higher in the HBcAg (-) group (both P < 0.05). Binary logistic regression analysis showed that HBcAg (-) was the predictor for the lack of HBeAg (OR 4.482, 95% CI: 1.58-12.68). In summary, the absence of HBcAg in the hepatocyte nucleus could be an independent predictor for HBeAg seroconversion rates during NA-naïve treatment in HBeAg (+) CHB patients.
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http://dx.doi.org/10.1111/jcmm.13444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824392PMC
March 2018

Comparing Efficacy of Lamivudine, Adefovir Dipivoxil, Telbivudine, and Entecavir in Treating Nucleoside Analogues Naïve for HBeAg-Negative Hepatitis B with Medium Hepatitis B Virus (HBV) DNA Levels.

Med Sci Monit 2017 Nov 2;23:5230-5236. Epub 2017 Nov 2.

Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China (mainland).

BACKGROUND The antiviral effect of HBV in different nucleos (t) ide analogues is still not well known. This study was conducted to compare the effectiveness of lamivudine (LMV), adefovir dipivoxil (ADV), telbivudine (LdT), and entecavir (ETV) monotherapy in chronic HBeAg-negative hepatitis B patients with medium load of HBV DNA. MATERIAL AND METHODS The effective data of 207 patients treated by LMV (n=43), ADV (n=57), LdT (n=54) or ETV (n=53) were collected and analyzed during 144-week follow-up by retrospective analysis. RESULTS Serum HBV DNA levels were significantly lower in the ETV group 1.91±0.45 log10 IU/ml) than in the LdT group (2.09±0.62 log10 IU/ml), ADV group (2.26±0.73 log10 IU/ml), and LMV group (2.08±0.75 log10 IU/ml) at 12 weeks (P=0.0464). HBV DNA levels were maintained at lower levels in the ETV group compared to other 3 groups during follow-up (48 weeks, P<0.001; 96 weeks, P<0.001). Multivariate Cox regression analysis showed that LMV (P=0.001), ADV, (P<0.001), and LdT (P<0.001) were all negative predictors of HBV DNA-negative time, but ETV was not. Viral breakthrough occurred in 34.8% (15/43) of patients in the LMV group; 5.26% (3/57) in the ADV group, 7.4.0% (4/54) in the LdT group, and 0% (0/53) in the ETV group at the end of follow-up. No significant differences were found in mean ALT levels (all P>0.05) or in cumulative normalization rates (P=0.473). CONCLUSIONS ETV was more potent and faster for viral response and lower viral breakthrough in medium load of HBV DNA when compared to LMV, ADV, or LdT monotherapy in HBeAg-negative CHB.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680675PMC
http://dx.doi.org/10.12659/msm.903382DOI Listing
November 2017

miR-106a Is Downregulated in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B and Associated with Enhanced Levels of Interleukin-8.

Mediators Inflamm 2015 22;2015:629862. Epub 2015 Jul 22.

Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong 519000, China.

Aims: This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a.

Materials And Methods: miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3'UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively.

Results: The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects.

Conclusions: This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.
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http://dx.doi.org/10.1155/2015/629862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525765PMC
May 2016

Chemokine-like factor 1-derived C-terminal peptides induce the proliferation of dermal microvascular endothelial cells in psoriasis.

PLoS One 2015 27;10(4):e0125073. Epub 2015 Apr 27.

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

Psoriasis is an inflammatory disease characterized by the abnormal proliferation of skin cells, including dermal microvascular endothelial cells. Recently, chemokine-like factor 1 (CKLF1) was found to participate in the local inflammation and cell proliferation. To explore its role in the pathogenesis of psoriasis, the expression of both CKLF1 and its receptor (CCR4) was determined in the psoriatic lesions. Also, the effect of the C-terminal peptides (C19 and C27) of CKLF1 on the proliferation of human umbilical vein endothelial cells was studied in vitro. By immunohistochemistry and immunofluorescence, the expression of both CKLF1 and CCR4 was determined in the psoriatic lesions. The effect of C-terminal peptides on human umbilical vein endothelial cells (HUVECs) was studied in vitro by the evaluation of cell proliferation and apoptosis. The in vivo assessment was performed accordingly through the subcutaneous injection peptides on BALB/c mice. The results showed that, by immunohistochemistry, both CKLF1 and CCR4 were increasingly expressed in psoriatic lesions as compared to normal skins. Moreover, the primary umbilical vein endothelial cells exhibited higher proliferation ratio under the C19 or C27 stimulation, which was even enhanced by the addition of psoriatic sera or TNF-α. Furthermore, the enhancement of peptide simulation was accompanied with the activation of ERK1/2-MAPKs pathway. In addition, such effect of C19 and C27 was mirrored by the hyperproliferation of cutaneous microvessels in BALB/c mice that were subcutaneously injected with the two peptides. Therefore, we concluded that CKLF1 plays a role in the pathogenesis of psoriasis by promoting the proliferation of microvascular endothelial cells that possibly correlates with ERK1/2-MAPKs activation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0125073PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410955PMC
April 2016

[Retrospective analysis of the efficacy and safety of anti-hepatitis B virus drugs taken during pregnancy in women from the Guangdong Province].

Zhonghua Gan Zang Bing Za Zhi 2014 Jul;22(7):490-2

Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China.

Objective: To investigate the efficacy of anti-hepatitis B virus (HBV) drugs for preventing vertical transmission of HBV and the safety of these drugs when given as treatment during pregnancy (to women) or insemination (to men).

Methods: Cases of women and men who had taken anti-HBV drug therapy during pregnancy or insemination, respectively, were retrospectively selected for study from among 18 hospitals and 33 specialists in the Guangdong Province. Demographic, HBV infection and treatment data was collected for puerperal men or women and their newborns from the medical records.

Results: A total of 122 cases with detailed follow-up data were included in the study and including 74 women who were administered lamivudine (LAM) more than telbivudine (LdT) more than adefovir (ADV)more than entecavir (ETV) (hierarchy ranking by number of cases) and 48 men who were administered LAM more than ADV more than LdT more than ETV.None of the 122 newborns related to these cases showed HBV infection at 7 months of follow-up.None of the 74 puerperal women showed complications related to reproduction.There was one ease of a newborn being underweight at birth (2.1 kg), for which the mother had taken LdT during pregnancy. There was also one case of a newborn with a harelip and one case of a newborn with an inguinal hernia, for which both of the fathers had taken ADV during the time of insemination.

Conclusion: This retrospective investigation carried out in Guangdong Province indicated that not only are anti-HBV drugs efficacious for blocking vertical transmission of HBV but also are safe for both mothers and infants when taken by fathers or mothers during the reproduction phases of insemination and pregnancy.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2014.07.003DOI Listing
July 2014

Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy.

Cell Metab 2008 Nov;8(5):411-24

Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

Mammalian target of rapamycin (mTOR) is a central controller of cell growth. mTOR assembles into two distinct multiprotein complexes called mTOR complex 1 (mTORC1) and mTORC2. Here we show that the mTORC1 component raptor is critical for muscle function and prolonged survival. In contrast, muscles lacking the mTORC2 component rictor are indistinguishable from wild-type controls. Raptor-deficient muscles become progressively dystrophic, are impaired in their oxidative capacity, and contain increased glycogen stores, but they express structural components indicative of oxidative muscle fibers. Biochemical analysis indicates that these changes are probably due to loss of activation of direct downstream targets of mTORC1, downregulation of genes involved in mitochondrial biogenesis, including PGC1alpha, and hyperactivation of PKB/Akt. Finally, we show that activation of PKB/Akt does not require mTORC2. Together, these results demonstrate that muscle mTORC1 has an unexpected role in the regulation of the metabolic properties and that its function is essential for life.
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http://dx.doi.org/10.1016/j.cmet.2008.10.002DOI Listing
November 2008

Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45.

Proc Natl Acad Sci U S A 2007 Dec 5;104(50):20108-13. Epub 2007 Dec 5.

Departments of Anaesthesia and Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.

Skeletal muscle constitutes approximately 40% of the human body mass, and alterations in muscle mass and strength may result in physical disability. Therefore, the elucidation of the factors responsible for muscle force development is of paramount importance. Excitation-contraction coupling (ECC) is a process during which the skeletal muscle surface membrane is depolarized, causing a transient release of calcium from the sarcoplasmic reticulum that activates the contractile proteins. The ECC machinery is complex, and the functional role of many of its protein components remains elusive. This study demonstrates that deletion of the gene encoding the sarcoplasmic reticulum protein JP45 results in decreased muscle strength in young mice. Specifically, this loss of muscle strength in JP45 knockout mice is caused by decreased functional expression of the voltage-dependent Ca(2+) channel Ca(v)1.1, which is the molecule that couples membrane depolarization and calcium release from the sarcoplasmic reticulum. These results point to JP45 as one of the molecules involved in the development or maintenance of skeletal muscle strength.
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http://dx.doi.org/10.1073/pnas.0707389104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2148430PMC
December 2007

SRP-27 is a novel component of the supramolecular signalling complex involved in skeletal muscle excitation-contraction coupling.

Biochem J 2008 Apr;411(2):343-9

Department of Experimental and Diagnostic Medicine, General Pathology section, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.

SRP-27 (sarcoplasmic reticulum protein of 27 kDa) is a newly identified integral membrane protein constituent of the skeletal muscle SR (sarcoplasmic reticulum). We identified its primary structure from cDNA clones isolated from a mouse skeletal muscle cDNA library. ESTs (expressed sequence tags) of SRP-27 were found mainly in cDNA libraries from excitable tissues of mouse. Western blot analysis confirmed the expression of SRP-27 in skeletal muscle and, to a lower extent, in heart and brain. Mild trypsin proteolysis combined with primary-structure prediction analysis suggested that SRP-27 has four transmembrane-spanning alpha helices and its C-terminal domain faces the cytoplasmic side of the endo(sarco)plasmic reticulum. The expression of SRP-27 is higher in fast twitch skeletal muscles compared to slow twitch muscles and peaks during the first month of post-natal development. High-resolution immunohistochemistry and Western blot analysis of subcellular fractions indicated that SRP-27 is distributed in both longitudinal tubules and terminal cisternae of the SR, as well as in the perinuclear membrane systems and the nuclear envelope of myotubes and adult fibres. SRP-27 co-sediments with the RyR (ryanodine receptor) macromolecular complex in high-salt sucrose-gradient centrifugation, and is pulled-down by anti-RyR as well as by maurocalcin, a well characterized RyR modulator. Our results indicate that SRP-27 is part of a SR supramolecular complex, suggesting the involvement of SRP-27 in the structural organization or function of the molecular machinery underlying excitation-contraction coupling.
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http://dx.doi.org/10.1042/BJ20070906DOI Listing
April 2008