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1.
J Med Virol ; 95(1): e28163, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36127294

RESUMO

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.


Assuntos
Infecções Irruptivas , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Imunoglobulina G , Anticorpos Antivirais , Anticorpos Neutralizantes
2.
Virol J ; 20(1): 106, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37248496

RESUMO

BACKGROUND: The pathogenicity and virulence of the Omicron strain have weakened significantly pathogenesis of Omicron variants. Accumulating data indicated accessory proteins play crucial roles in host immune evasion and virus pathogenesis of SARS-CoV-2. Therefore, the impact of simultaneous deletion of accessory protein ORF7a, ORF7b and ORF8 on the clinical characteristics and specific immunity in Omicron breakthrough infected patients (BIPs) need to be verified. METHODS: Herein, plasma cytokines were identified using a commercial Multi-cytokine detection kit. Enzyme-linked immunosorbent assay and pseudovirus neutralization assays were utilized to determine the titers of SARS-CoV-2 specific binding antibodies and neutralizing antibodies, respectively. In addition, an enzyme-linked immunospot assay was used to quantify SARS-CoV-2 specific T cells and memory B cells. RESULTS: A local COVID-19 outbreak was caused by the Omicron BA.2 variant, which featured a deletion of 871 base pairs (∆871 BA.2), resulting in the removal of ORF7a, ORF7b, and ORF8. We found that hospitalized patients with ∆871 BA.2 had significantly shorter hospital stays than those with wild-type (WT) BA.2. Plasma cytokine levels in both ∆871 BA.2 and WT BA.2 patients were within the normal range of reference, and there was no notable difference in the titers of SARS-CoV-2 ancestor or Omicron-specific binding IgG antibodies, neutralizing antibody titers, effector T cells, and memory B cells frequencies between ∆871 BA.2 and WT BA.2 infected adult patients. However, antibody titers in ∆871 BA.2 infected adolescents were higher than in adults. CONCLUSIONS: The simultaneous deletion of ORF7a, ORF7b, and ORF8 facilitates the rapid clearance of the BA.2 variant, without impacting cytokine levels or affecting SARS-CoV-2 specific humoral and cellular immunity in Omicron-infected individuals.


Assuntos
COVID-19 , Adolescente , Adulto , Humanos , SARS-CoV-2/genética , Anticorpos Neutralizantes , Anticorpos Antivirais , Citocinas , ELISPOT
3.
BMC Anesthesiol ; 23(1): 364, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37936070

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of cardiac surgery that poses significant risks for both the development of chronic kidney diseases and mortality. Our previous study illustrated that heightened expression levels of faecal and plasma indole metabolites before the operation were associated with ischemic AKI. In this study, we aimed to validate the supposition that plasma indole-3-aldehyde (I3A) could serve as a predictive biomarker for AKI in patients undergoing cardiac surgery. METHODS: This statistical reanalysis utilized AKI metabolomic data from patients scheduled for cardiac surgery between April 2022 and July 2022 in two tertiary hospitals. Faecal and blood samples were prospectively collected before surgery within 24 h, and variables related to the preoperative, intraoperative, and postoperative periods were recorded. AKI diagnosis was based on the Kidney Disease Improving Global Outcomes criteria. RESULTS: In this study, 55 patients who underwent cardiac surgery were analyzed, and 27 of them (49.1%) developed postoperative AKI. Before surgery, these patients had significantly higher levels of faecal indole metabolites, including skatole, trans-3-indoleacrylic acid, and 5-methoxyindoleacetic acid. The plasma I3A, clinical model that considered perioperative and intraoperative variables, and their combination had area under the receiver operating characteristic curve (ROC) values of 0.79 (95% CI 0.67-0.91), 0.78 (95% CI 0.66-0.90), and 0.84 (95% CI 0.74-0.94) for predicting AKI, respectively. Furthermore, by utilizing net reclassification improvement and integrated discrimination improvement, plasma I3A showed significant improvements in risk reclassification compared to the clinical model alone. CONCLUSIONS: The dysregulation of gut microbiota metabolism in patients scheduled for cardiac surgery can result in an increase in indoles from tryptophan metabolism, which may be associated with postoperative acute kidney injury (AKI). This suggests that indoles may serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Estudos Prospectivos , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Biomarcadores , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Indóis
4.
Cancer Cell Int ; 20(1): 555, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33292228

RESUMO

BACKGROUND: To establish and validate a multi-parametric prognostic model based on clinical features and serological markers to estimate the overall survival (OS) in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. METHODS: The prognostic model was established by using Lasso regression analysis in the training cohort. The incremental predictive value of the model compared to traditional TNM staging and clinical treatment for individualized survival was evaluated by the concordance index (C-index), time-dependent ROC (tdROC) curve, and decision curve analysis (DCA). A prognostic model risk score based nomogram for OS was built by combining TNM staging and clinical treatment. Patients were divided into high-risk and low-risk subgroups according to the model risk score. The difference in survival between subgroups was analyzed using Kaplan-Meier survival analysis, and correlations between the prognostic model, TNM staging, and clinical treatment were analysed. RESULTS: The C-index of the model for OS is 0.769 in the training cohorts and 0.676 in the validation cohorts, respectively, which is higher than that of TNM staging and clinical treatment. The tdROC curve and DCA show the model have good predictive accuracy and discriminatory power compare to the TNM staging and clinical treatment. The prognostic model risk score based nomogram show some net clinical benefit. According to the model risk score, patients are divided into low-risk and high-risk subgroups. The difference in OS rates is significant in the subgroups. Furthermore, the model show a positive correlation with TNM staging and clinical treatment. CONCLUSIONS: The prognostic model showed good performance compared to traditional TNM staging and clinical treatment for estimating the OS in NSCLC (HBV+) patients.

5.
Clin Med Insights Case Rep ; 16: 11795476231183318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363276

RESUMO

Coronary perforation (CP) is a rare complication of percutaneous coronary intervention (PCI) and can lead to pericardial tamponade. Prolonged balloon inflation is a reasonable treatment for CP, but there is no standard recommendation on the preferable choice between the balloon site for prolonged balloon inflation (ie, proximal and in situ of the perforation). We present a rare case of successful prolonged balloon inflation at the proximal site of the CP after the failure of balloon inflation at the site of perforation. The patient developed CP during balloon inflation post-stent, rapidly progressing to cardiac tamponade. In situ prolonged balloon inflation (3 times) failed to close the CP, but proximal inflation could manage the CP. The take-home message from this case is that balloon expansion at the proximal site could be better than in situ of perforation in patients with CP after PCI.

6.
Life Sci ; 332: 122078, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37734435

RESUMO

AIMS: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive and lethal malignancies with an extremely poor prognosis. It is necessary to explore the molecular mechanisms of ESCC invasion. MAIN METHODS: We utilized high-throughput mass spectrometry to analyze the proteomes and phosphorylation profiles of two ESCC cell lines with differing invasion capacities (HK vs TE10). Differentially expressed proteins and phosphorites were identified, followed by comprehensive bioinformatics analyses encompassing function and pathway enrichment, protein-protein interaction (PPI) network analysis, hub gene identification, co-expression analysis, kinase-substrate prediction, and drug-target network analysis. CCK-8 assay, transwell examination, wound-healing assay, and western blot was used to validate the effects of fostamatinib on ESCC cells proliferation, invasion, migration, and LYN expression. KEY FINDINGS: The Q4 cluster of differentially phosphorylated proteins was primarily associated with functions and pathways relevant to tumor metastasis. Phosphorylated hub proteins including ARHGAP35, CTNNA1, and SHC1 were identified through the analysis of PPI network, and their respective regulated kinases were predicted. Among the predicted kinases, LYN was validated to be associated with lymph node metastasis (N0 vs. N1-3) and prognosis in ESCC patients at mRNA levels using TGGA data and protein levels in ESCC tissues (p < 0.05). Validation experiments confirmed the inhibitory effects of fostamatinib on ESCC cells proliferation, migration, invasion, and LYN expression. SIGNIFICANCE: Our multi-omics analysis offers deeper perspectives on ESCC invasiveness and unveils new phosphorylated hub proteins with their regulatory kinase. This study also suggests that fostamatinib may be a potential agent for treating ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteômica , Movimento Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genética
7.
Virol Sin ; 38(2): 233-243, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36603767

RESUMO

Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.


Assuntos
Infecções Irruptivas , COVID-19 , Humanos , SARS-CoV-2 , Anticorpos , Anticorpos Antivirais , Anticorpos Neutralizantes
8.
Sci Rep ; 13(1): 7263, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142713

RESUMO

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.


Assuntos
COVID-19 , Transplante de Rim , Feminino , Humanos , Masculino , Tacrolimo , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Imunidade Celular , Bilirrubina , Imunidade Humoral , Transplantados , Vacinação , Anticorpos Antivirais
9.
Front Immunol ; 13: 1042784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36700230

RESUMO

Background: A third mRNA vaccine booster is recommended to improve immunity against SARS-CoV-2 in kidney transplant recipients (KTRs). However, the immunity against SARS-CoV-2 Ancestral strain and Delta and Omicron variants elicited by the third dose of inactivated booster vaccine in KTRs remains unknown. Methods: The blood parameters related to blood cells count, hepatic function, kidney function, heart injury and immunity were explored clinically from laboratory examinations. SARS-CoV-2 specific antibody IgG titer was detected using an enzyme-linked immunosorbent assay. Cellular immunity was analyzed using interferon-γ enzyme-linked immunospot assay. Results: The results showed that there were no severe adverse effects and apparent changes of clinical laboratory biomarkers in KTRs and healthy volunteers (HVs) after homologous inactivated vaccine booster. A third dose of inactivated vaccine booster significantly increased anti-Ancestral-spike-trimer-IgG and anti-Ancestral-receptor binding domain (RBD)-IgG titers in KTRs and HVs compared with the second vaccination. However, the anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG titers were significantly lower than anti-Ancestral-RBD-IgG titer in KTRs and HVs after the third dose. Notably, only 25.6% (10/39) and 10.3% (4/39) of KTRs had seropositivity for anti-Delta-RBD-IgG and anti-Omicron-RBD-IgG after booster, which were significantly lower than HVs (anti-Delta-RBD-IgG: 100%, anti-Omicron-RBD-IgG: 77.8%). Ancestral strain nucleocapsid protein and spike specific T cell frequency after booster was not significantly increased in KTRs compared with the second dose, significantly lower than that in HVs. Moreover, 33.3% (12/36), 14.3% (3/21) and 14.3% (3/21) of KTRs were positive for the Ancestral strain and Delta and Omicron spike-specific T cells, which were significantly lower than HVs (Ancestral: 80.8%, Delta: 53.8%, and Omicron: 57.7%). Conclusions: A third dose of inactivated booster vaccine may significantly increase humoral immunity against the Ancestral strain in KTRs, while humoral and cellular immunity against the Delta and Omicron variants were still poor in KTRs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Rim , Humanos , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/prevenção & controle , ELISPOT , Imunoglobulina G , SARS-CoV-2 , Imunização Secundária , Vacinas contra COVID-19/imunologia
10.
Oncol Res ; 29(6): 401-409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37304650

RESUMO

It has been certified that GABPB1-AS1 is aberrantly expressed and plays as a vital role in some kinds of cancers. However, its expression pattern and functions in non-small cell lung cancer (NSCLC) are still largely unknown. This study aims to assess GABPB1-AS1 expression and biological roles in NSCLC. The expression of GABPB1-AS1 was detected in NSCLC specimens and adjacent normal specimens. CCK8 and Transwell assays were performed to evaluate the effects of GABPB1-AS1 on NSCLC cell proliferation, migration and invasion. Bioinformatics tools and luciferase reporter assays were applied to predict and verify GABPB1-AS1's direct targets. The results revealed that GABPB1-AS1 is sharply reduced in NSCLC specimens and cell lines. CCK8 assays indicated that overexpression of GABPB1-AS1 dramatically reduced NSCLC cell growth, and Transwell assays proved that NSCLC cell migration and invasion were distinctly inhibited by GABPB1-AS1. Exploration of the mechanism uncovered that miRNA-566 (miR-566)/F-box protein 47 (FBXO47) is directly targeted by GABPB1-AS1 in NSCLC. The study demonstrated that GABPB1-AS1 inhibited NSCLC cell proliferation, migration and invasion by targeting miR-566/FBXO47.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Proteínas F-Box , Neoplasias Pulmonares , MicroRNAs , Humanos , MicroRNAs/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Linhagem Celular , Fator de Transcrição de Proteínas de Ligação GA , Fatores de Transcrição
11.
Biosci Rep ; 41(3)2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33635316

RESUMO

BACKGROUND: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood. METHODS: In the present study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison. RESULTS: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters (ChE). Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways. CONCLUSIONS: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to undergo consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.


Assuntos
COVID-19/sangue , Dislipidemias/epidemiologia , Lipídeos/sangue , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lipidômica , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Plasma , Sobreviventes , Adulto Jovem
12.
Cancer Med ; 10(11): 3511-3523, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33973727

RESUMO

This study aims to develop and validate a novel prognostic model to estimate overall survival (OS) in nasopharyngeal carcinoma (NPC) patients based on clinical features and blood biomarkers. We assessed the model's incremental value to the TNM staging system, clinical treatment, and Epstein-Barr virus (EBV) DNA copy number for individual OS estimation. We retrospectively analyzed 519 consecutive patients with NPC. A prognostic model was generated using the Lasso regression model in the training cohort. Then we compared the predictive accuracy of the novel prognostic model with TNM staging, clinical treatment, and EBV DNA copy number using concordance index (C-index), time-dependent ROC (tdROC), and decision curve analysis (DCA). Subsequently, we built a nomogram for OS incorporating the prognostic model, TNM staging, and clinical treatment. Finally, we stratified patients into high-risk and low-risk groups according to the model risk score, and we analyzed the survival time of these two groups using Kaplan-Meier survival plots. All results were validated in the independent validation cohort. Using the Lasso regression, we established a prognostic model consisting of 13 variables with respect to patient prognosis. The C-index, tdROC, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort than did TNM staging, clinical treatment, and EBV DNA copy number. Nomogram consisting of the prognostic model, TNM staging, clinical treatment, and EBV DNA copy number showed some superior net benefit. Based on the model risk score, we split the patients into two subgroups: low-risk (risk score ≤ -1.423) and high-risk (risk score > -1.423). There were significant differences in OS between the two subgroups of patients. Similar results were observed in the validation cohort. The proposed novel prognostic model based on clinical features and serological markers may represent a promising tool for estimating OS in NPC patients.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Nomogramas , Biomarcadores Tumorais/sangue , Estudos de Coortes , Variações do Número de Cópias de DNA , DNA Viral/genética , Técnicas de Apoio para a Decisão , Feminino , Herpesvirus Humano 4/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Estadiamento de Neoplasias , Prognóstico , Análise de Regressão , Estudos Retrospectivos
13.
Front Immunol ; 12: 664619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305895

RESUMO

Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18-25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.


Assuntos
COVID-19/imunologia , COVID-19/virologia , RNA Viral/isolamento & purificação , Imunidade Adaptativa , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Soroconversão , Glicoproteína da Espícula de Coronavírus/imunologia
14.
Cancer Manag Res ; 12: 3091-3097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440207

RESUMO

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is an aggressive human malignancy. Long non-coding RNAs (lncRNAs) are critical regulators in many malignant tumors, including ccRCC. The aim of this study is to investigate the expression, functions and molecular mechanisms of lncRNA TTN-AS1 in ccRCC. METHODS: A total of 145 paired cancer and normal tissues were collected from patients with ccRCC. The expression levels of TTN-AS1 and miR-195 in the tissues or cells were measured by RT-qPCR analysis. The expression levels of cyclin D1 protein were measured by Western blot analysis. Cell proliferation and cell cycle distribution were detected by MTT assay and flow cytometer analysis, respectively. The binding relationship between miR-195 and TTN-AS1 or cyclin D1 mRNA was validated by dual-luciferase reporter assay. RESULTS: Our results revealed that TTN-AS1 expression levels in human ccRCC tissues and cell lines were markedly increased. High expression of TTN-AS1 was closely associated with adverse clinicopathological characteristics of ccRCC patients. Gain- and loss-of-function experiments showed that TTN-AS1 overexpression promoted the proliferation and cell cycle transition of ccRCC cells, while the malignant traits were obviously suppressed after TTN-AS1 knockdown. Mechanistically, miR-195 was found to bind with and to be negatively regulated by TTN-AS1 in ccRCC cells. Further, we showed that cyclin D1 is a direct target of miR-195 in ccRCC, and rescue assays verified that restoration of miR-195 expression partially blocked the oncogenic effects of TTN-AS1 in ccRCC cells. CONCLUSION: Our study provides a novel mechanism of TTN-AS1/miR-195/cyclin D1 regulatory axis in ccRCC, which may become a breakthrough for ccRCC therapy in the future.

15.
Clin Transl Med ; 9(1): 2, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907639

RESUMO

BACKGROUND: Serum amyloid A (SAA) has been associated with the development and prognosis of cancer. The purpose of this study was to evaluate the predictive value of integration of pretreatment SAA-EBV DNA (S-D) grade and comparison with the TNM staging system in patients with nasopharyngeal carcinoma (NPC). The S-D grade was calculated based on the cut-off values of serum SAA and EBV DNA copy numbers which were determined by receiver operating characteristic (ROC) curves. We evaluated the prognostic value of pretreatment SAA, EBV DNA and S-D grade on overall survival (OS) of NPC patients. We also evaluated the predictive power of S-D grade with TNM staging system using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 304 NPC patients were enrolled in this study. Multivariate analysis showed that TNM stage (P = 0.007), SAA (P = 0.013), and EBV DNA (P = 0.033) were independent prognostic factors in NPC. The S-D grade was divided into S-D grade 1, S-D grade 2, and S-D grade 3, which had more predictive accuracy for OS than TNM staging according to all 4 indices. CONCLUSIONS: We found that the S-D grade could be used as a new tool to predict the OS in NPC patients.

16.
Biosens Bioelectron ; 166: 112455, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739797

RESUMO

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) worldwide pandemic. This unprecedented situation has garnered worldwide attention. An effective strategy for controlling the COVID-19 pandemic is to develop highly accurate methods for the rapid identification and isolation of SARS-CoV-2 infected patients. Many companies and institutes are therefore striving to develop effective methods for the rapid detection of SARS-CoV-2 ribonucleic acid (RNA), antibodies, antigens, and the virus. In this review, we summarize the structure of the SARS-CoV-2 virus, its genome and gene expression characteristics, and the current progression of SARS-CoV-2 RNA, antibodies, antigens, and virus detection. Further, we discuss the reasons for the observed false-negative and false-positive RNA and antibody detection results in practical clinical applications. Finally, we provide a review of the biosensors which hold promising potential for point-of-care detection of COVID-19 patients. This review thereby provides general guidelines for both scientists in the biosensing research community and for those in the biosensor industry to develop a highly sensitive and accurate point-of-care COVID-19 detection system, which would be of enormous benefit for controlling the current COVID-19 pandemic.


Assuntos
Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Anticorpos Antivirais/isolamento & purificação , Antígenos Virais/isolamento & purificação , Betacoronavirus/genética , Betacoronavirus/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/tendências , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/instrumentação , Técnicas de Laboratório Clínico/tendências , Infecções por Coronavirus/epidemiologia , Desenho de Equipamento , Genoma Viral , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Pneumonia Viral/epidemiologia , Testes Imediatos , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Vírion/isolamento & purificação
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