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1.
Front Immunol ; 13: 822616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359986

RESUMO

The AID/APOBEC family which converts cytidine to uridine on RNA or DNA experienced dynamic expansion in primates in order to resist exogenous viruses and endogenous retrotransposons. Recently, expansion of AID/APOBEC-like homologs has also been observed in the extant jawless vertebrate lamprey. To reveal what causes such expansion and leads to the functional diversification of lamprey cytosine deaminases (CDAs), we reassessed the CDA genes in Lethenteron japonicum (Lj). We first confirmed the expansion of LjCDA1L1 (CDA1-like 1) genes and found the expression correlation of LjCDA2 and LjCDA1L2 with LjVLRs (variable lymphocyte receptors). Among up to 14 LjCDA1L1 proteins, LjCDA1L1_4a has an extremely high deamination activity on ssDNA and buDNA and, unexpectedly, on dsDNA. LjCDA1L1s can also restrict the infection of HSV-1 particles. Thus, the arms race between the host and pathogens along with the recruitment by VLR assembly may participate together to form a driving force in the expansion and diversification of the lamprey AID/APOBEC family.


Assuntos
Citidina Desaminase , Lampreias , Animais , Citidina , Citidina Desaminase/genética , DNA/metabolismo , Lampreias/genética , Lampreias/metabolismo , Vertebrados/metabolismo
2.
BMC Infect Dis ; 22(1): 17, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983415

RESUMO

BACKGROUND: Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. METHODS: This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. RESULTS: Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). CONCLUSIONS: DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Lamivudina/uso terapêutico , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , Tenofovir/uso terapêutico
3.
J Med Virol ; 93(2): 952-961, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32725915

RESUMO

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 PO2 < 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 PO2 < 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.


Assuntos
COVID-19/fisiopatologia , COVID-19/virologia , SARS-CoV-2/patogenicidade , Eliminação de Partículas Virais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Fezes/virologia , Feminino , Febre/virologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Razão de Chances , Sistema Respiratório/virologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Adulto Jovem
4.
Infect Dis Poverty ; 9(1): 163, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33261654

RESUMO

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.


Assuntos
COVID-19/patologia , COVID-19/virologia , Influenza Humana/patologia , Influenza Humana/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/mortalidade , Criança , Pré-Escolar , Comorbidade , Progressão da Doença , Feminino , Hospitalização , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Influenza Humana/diagnóstico , Influenza Humana/mortalidade , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/patogenicidade , Eliminação de Partículas Virais , Adulto Jovem
5.
Int J Med Sci ; 17(16): 2561-2569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029098

RESUMO

Background: During the outbreak period of COVID-19 pneumonia, cancer patients have been neglected and in greater danger. Furthermore, the differential diagnosis between COVID-19 pneumonia and radiation pneumonitis in cancer patients remains a challenge. This study determined their clinical presentations and radiological features in order to early diagnose and separate COVID-19 pneumonia from radiation pneumonitis patients promptly. Methods and Findings: From January 21, 2020 to February 18, 2020, 112 patients diagnosed with suspected COVID-19 were selected consecutively. A retrospective analysis including all patients' presenting was performed. Four patients from 112 suspected individals were selected, including 2 males and 2 females with a median age of 54 years (range 39-64 years). After repeated pharyngeal swab nucleic acid tests, 1 case was confirmed and 3 cases were excluded from COVID-19 pneumonia. Despite the comparable morphologic characteristics of lung CT imaging, the location, extent, and distribution of lung lesions between COVID-19 pneumonia and radiation pneumonitis differed significantly. Conclusions: Lung CT imaging combined with clinical and laboratory findings can facilitate early diagnosis and appropriate management of COVID-19 pneumonia with a history of malignancy and radiation therapy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Diagnóstico Diferencial , Neoplasias/radioterapia , Pneumonia Viral/diagnóstico por imagem , Pneumonite por Radiação/diagnóstico por imagem , Adulto , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias/virologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X
6.
J Infect ; 81(1): e1-e5, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32171872

RESUMO

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.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Administração Oral , Adulto , Antivirais/administração & dosagem , COVID-19 , Estudos de Coortes , Infecções por Coronavirus/diagnóstico por imagem , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Indóis/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Estudos Retrospectivos , Ritonavir/administração & dosagem , Tomografia Computadorizada por Raios X
7.
Hum Gene Ther ; 27(11): 880-891, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27136973

RESUMO

Liver fibrosis results in cirrhosis, liver cancer, and liver failure, which is a major cause of mortality worldwide. Gene therapy is a relatively new paradigm in medicine, with enormous therapeutic potential. The development of an efficient and safe delivery system is essential for clinical gene therapy. In the present study, we evaluated augmenter of liver regeneration/growth factor ERV1-like (ALR/GFER) gene therapeutic effect mediated by a novel minicircle vector (MC-hALR). The results in liver fibrotic rats that received MC-hALR through hydrodynamics-based transfection (HBT) for 8 weeks indicated that the minicircle DNA vector produced a more effective gene therapy effect than traditional plasmids (pcDNA3.1-hALR). Even when we reduced the treatment dose of MC-hALR to 30% (w/w) and the treatment frequency from weekly to biweekly, the in vitro and in vivo results still demonstrated that higher ALR gene expression significantly blocked increases in transforming growth factor-ß1 (TGF-ß1), platelet derived growth factor-BB (PDGF-BB), and α-smooth muscle aorta (α-SMA) levels; effectively suppressed the production of collagens, especially collagen I; and effectively alleviated liver injury and fibrosis in rats, thereby improving the survival rate of liver fibrotic rats. It is preliminarily concluded that the relative overexpression of MC-hALR inhibits the activation of hepatic stellate cells (HSCs), thereby alleviating liver fibrosis in rats.


Assuntos
DNA Circular/genética , Proteínas de Ligação a DNA/genética , Terapia Genética , Vetores Genéticos/administração & dosagem , Células Estreladas do Fígado/citologia , Cirrose Hepática/genética , Cirrose Hepática/terapia , Proteínas de Neoplasias/genética , Animais , Regeneração Hepática , Masculino , Ratos , Ratos Sprague-Dawley
8.
ScientificWorldJournal ; 2014: 103643, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24999489

RESUMO

BACKGROUND AND AIM: Adipose derived mesenchymal stem cells (ADMSCs) may be an attractive source for acute and chronic liver injury because they are abundant and easy to obtain. We aim to investigate the efficacy of ADMSCs transplantation in the acute liver failure (ALF) caused by carbon tetrachloride (CCl4) in mice. METHODS: ADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and their surface markers and differentiation potential were analyzed. ALF models were established by infusion of CCl4 and divided into two groups: control group; EGFP-ADMSCs transplantation group. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as survival rates, live function parameters, histological localization of EGFP-ADMSCs, and Immunofluorescence analysis. RESULTS: ADMSCs were positive for CD105, CD44 but negative for CD45, CD34 and had adipogenic, osteogenic differentiation potential. The survival rate of transplantation group significantly increased compared to PBS group. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin, cytokeratin-18. CONCLUSION: Direct transplantation of ADMSCs is an effective treatment for ALF. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers.


Assuntos
Tecido Adiposo/citologia , Tetracloreto de Carbono/toxicidade , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Adiposidade , Animais , Células Cultivadas , Receptores de Hialuronatos/metabolismo , Integrina beta4/metabolismo , Queratina-18/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
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