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The HIV latent reservoir is the main obstacle to the eradication of AIDS. Recent studies have shown that the RNA m6A is involved in the regulation of HIV-1 replication. However, no relevant study has reported the relationship between RNA m6A and HIV latent reservoir. For this purpose, peripheral blood mononuclear cell (PBMC) was collected from 36 HIV-infected patients at 1, 24, and 48 weeks after treatment initiation. The number of CD4+ and CD8+ T cells was detected by flow cytometry. Amount of HIV DNA in the PBMC samples one week after treatment initiation was detected by Q-PCR. The expression levels of 23 RNA-m6A-related genes were detected by Q-PCR and Pearson's correlation analysis was performed. Results showed that there was a negative correlation between HIV DNA concentration and the number of CD4+ T cells (r=-0.32, p=0.05; r=-0.32, p=0.06) and a positive correlation with the number of CD8+ T cells (r=0.48, p=0.003; r=0.37, p=0.03). Furthermore, a negative correlation was observed between HIV DNA concentration and the CD4+/CD8+ T cell ratio (r=-0.53, p=0.001; r=-0.51, p=0.001). RNAm6A related genes which correlated with HIV DNA concentration includedALKBH5 (r=-0.45, p=-0.006), METTL3 (r=0.73, p=2.76e-7), METTL16 (r=0.71, p=1.21e2.76e-06), YTHDF1 (r=0.47, p=0.004). Moreover, they have different degrees of correlation with numbers ofCD4+ and CD8+ T cell subsets, and the CD4+/CD8+T cell ratio. In addition, the expression of RBM15 was not correlated with HIV DNA concentration but was significantly negatively correlated with the number of CD4+T cells (r=-0.40, p=0.02). In conclusion, the expression of ALKBH5, METTL3, and METTL16 is correlated with the HIV DNA level, the levels of CD4+ and CD8+ T cell counts, and the CD4+/CD8+ T cell ratio. RBM15 is independent of HIV DNA level and negatively correlated with the number of CD4+T cells.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Humanos , Leucócitos Mononucleares , Infecções por HIV/genética , RNA , Linfócitos T CD8-Positivos , Linfócitos T CD4-Positivos , HIV-1/genética , MetiltransferasesRESUMO
Infectious diseases are a type of disease caused by pathogenic microorganisms. Although the discovery of antibiotics changed the treatment of infectious diseases and reduced the mortality of bacterial infections, resistant bacterial strains have emerged. Anti-infective therapy based on aetiological evidence is the gold standard for clinical treatment, but the time lag and low positive culture rate of traditional methods of pathogen diagnosis leads to relative difficulty in obtaining the evidence of pathogens. Compared with traditional methods of pathogenic diagnosis, next-generation and third-generation sequencing technologies have many advantages in the detection of pathogenic microorganisms. In this review, we mainly introduce recent progress in research on pathogenic diagnostic technology and the applications of sequencing technology in the diagnosis of pathogenic microorganisms. This review provides new insights into the application of sequencing technology in the clinical diagnosis of microorganisms.
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Bactérias/genética , Infecções Bacterianas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , HumanosRESUMO
BACKGROUND: The enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 is the motivation behind this investigation to study gene phenotypes and resistance-associated genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. RESULTS: The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that blaKPC-2 is responsible for phenotypic resistance in six CRKP strains that K. pneumoniae sequence type (ST11) is informed. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum ß-lactamase (ESBL)-producing genes. fosA gene is detected amongst all the CRKP strains. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae. CONCLUSIONS: ST11 is the main CRKP type, and blaKPC-2 is the dominant carbapenemase gene harbored by clinical CRKP isolates from current investigations. The SNP markers detected would be helpful for characterizing CRKP strain from general K. pneumoniae. The data provides insights into effective strategy developments for controlling CRKP and nosocomial infection reductions.
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Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Estudo de Associação Genômica Ampla , Genômica , Humanos , Anotação de Sequência Molecular , Filogenia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Effective antiretroviral therapy extends the survival of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome, but these patients remain at higher risk for heart diseases compared with the general population. Previous studies have suggested that HIV-1 glycoprotein 120 (gp120) may be associated with heart disease. However, the underlying mechanisms by which HIV-1 gp120-mediated myocardial injury occurs remain unknown. OBJECTIVE: The current study aimed to uncover the mechanism of C-C chemokine receptor 5 (CCR5) coreceptor (R5) HIV-1 gp120-induced myocardial injury. METHODS: Morphology analysis, determination of the percentage of cell apoptosis, as well as lactate dehydrogenase (LDH) and creatine kinase (CK) assays were used to analyze whether R5 HIV-1 gp120 induced myocardial cell injury. We analyzed the phosphorylation of p38 mitogen-activated protein kinase (MAPK) with the CCR5 antagonist D-Ala-peptide T-amide (DAPTA) and NMDA receptor antagonist MK801, detected LDH and CK assays with p38 MAPK antagonist SB203580 (SB), and detected the percentage of cell apoptosis and death with DAPTA to investigate the mechanism of R5 HIV-1 gp120-induced myocardial cell injury. RESULTS: R5 HIV-1 gp120 damaged myocardial cells and induced p38 MAPK phosphorylation. SB blocked R5 HIV-1 gp120-induced myocardial cell injury. DAPTA blocked R5 HIV-1 gp120-mediated p38 MAPK phosphorylation, while MK801 did not. DAPTA inhibited R5 HIV-1 gp120-induced myocardial cell injury. CONCLUSION: Our data indicate that R5 HIV-1 gp120 activated p38 MAPK to trigger myocardial cell injury by the CCR5 coreceptor.
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Proteína gp120 do Envelope de HIV/genética , Miócitos Cardíacos/patologia , Receptores CCR5/genética , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Células Cultivadas , Feminino , HIV-1 , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Receptores CCR5/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
During March and April 2016, 11 yellow fever cases were identified in China. We report epidemic and viral information for 10 of these patients, 6 of whom had been vaccinated before travel. Phylogenetic analyses suggest these viruses nested within the diversity of strains endemic to Angola, where an outbreak began in 2015.
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Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/prevenção & controle , Surtos de Doenças , Vacinação , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Vírus da Febre Amarela , Angola/epidemiologia , China/epidemiologia , Doenças Transmissíveis Importadas/imunologia , Surtos de Doenças/prevenção & controle , Humanos , Filogenia , Vigilância em Saúde Pública , Vacinas Virais/imunologia , Febre Amarela/imunologia , Febre Amarela/virologia , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/imunologiaRESUMO
BACKGROUND: Talaromyces marneffei (TM) is an emerging pathogenic fungus that can cause a fatal systemic mycosis in patients infected with human immunodeficiency virus (HIV). Although global awareness regarding HIV/TM coinfection is increasing little is known about the mechanism that mediates the rapid progression to HIV/AIDS disease in coinfected individuals. The aim of this study was to analyze the serum proteome of HIV/TM coinfected patients and to identify the associated protein biomarkers for TM in patients with HIV/AIDS. METHODS: We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in the serum samples from HIV/TM-coinfected patients. RESULTS: Of a total data set that included 1099 identified proteins, approximately 86% of the identified proteins were quantified. Among them, 123 proteins were at least 1.5-fold up-or downregulated in the serum between HIV/TM-coinfected and HIV-mono-infected patients. Furthermore, our results indicate that two selected proteins (IL1RL1 and THBS1) are potential biomarkers for distinguishing HIV/TM-coinfected patients. CONCLUSIONS: This is the first report to provide a global proteomic profile of serum samples from HIV/TM-coinfected patients. Our data provide insights into the proteins that are involved as host response factors during infection. These data shed new light on the molecular mechanisms that are dysregulated and contribute to the pathogenesis of HIV/TM coinfection. IL1RL1 and THBS1 are promising diagnostic markers for HIV/TM-coinfected patients although further large-scale studies are needed. Thus, quantitative proteomic analysis revealed molecular differences between the HIV/TM-coinfected and HIV-mono-infected individuals, and might provide fundamental information for further detailed investigations.
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BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS: We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Transcriptoma/genética , HIV , Infecções por HIV/genética , Leucócitos Mononucleares/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Replicação Viral , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
Purpose: This study aimed to investigate the epidemiology and etiological spectrums of BSI in Fujian over the past 6 years in the post antiretroviral treatment (ART) era. Methods: A retrospective, observational study was conducted to include positive BSI inpatients with HIV between September 2015 and August 2021 in Mengchao Hepatobiliary Hospital of Fujian Medical University, the largest designated HIV/AIDS care hospital in Fujian, China. Demographic data and laboratory data including gender, age, blood cell counts, biochemistry results, CD4 and CD8 cell counts, HIV-RNA loads, pathogen isolates, procalcitonin (PCT) levels and c-reactive protein (CRP) levels were collected. Continuous variables were expressed as median (range) and Kruskal-Wallis or Mann-Whitney test was used to analyze the differences between groups. Categorical data were expressed as numbers (percentage) and the differences between groups were analyzed by Pearson's chi-squared test. Results: In total, 3681 HIV inpatients with blood culture data were included and 683 strains identified from 646 inpatients were further analyzed. The median age of patients was 38 years and male accounted for 86.84%. The pooled prevalence of BSI was 18.55% (12.01%-22.36% during the six-year period). The overall isolated rate of Talaromyces marneffei (TM) in blood culture was 12.42% (8.3%-15.00% during the study period). TM was the persistent dominant BSI pathogen from 2015 to 2021 (accounting for 63.04% to 71.43%), followed by Cryptococcus neoformans (responsible for 10.00% to 20.83%). Compared to patients with other organisms BSI, those with TM BSI were younger and had lower CD4 counts, WBC counts, HB and CRP level, but higher HIVRNA loads. Conclusion: BSI is still a major problem in the post ART era in hospitalized patients with HIV/AIDS in Fujian, China. TM is the predominant pathogen. This underlines the importance of an early diagnosis of opportunistic pathogen to avoid BSI in HIV-infected populations with a low immune status.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has becoming globally public health threat. Recently studies were focus on SARS-CoV-2 RNA to design vaccine and drugs. It was demonstrated that virus RNA could play as sponge to host noncoding RNAs to regulate cellular processes. Bioinformatic research predicted a series of motif on SARS-CoV-2 genome where are targets of human miRNAs. In this study, we used dual-luciferase reporter assays to validate the interaction between 3'UTR of SARS-CoV-2 S (S-3'UTR) gene and bioinformatic predicted targeting miRNAs. The growth of 293T cells and HUVECs with overexpressed S-3'UTR was determined, while miRNAs and IL6, TNF-α levels were checked in this condition. Then, miR-296 and miR-602 mimic were introduced into 293T cells and HUVECs with overexpressed S-3'UTR, respectively, to reveal the underlying regulation mechanism. In results, we screened 19 miRNAs targeting the S-3'UTR, including miR-296 and miR-602. In 293T cell, S-3'UTR could inhibit 293T cell growth through down-regulation of miR-296. By reducing miR-602, S-3'UTR could induce HUVECs cell proliferation, alter the cell cycle, reduce apoptosis, and enhanced IL6 and TNF-αlevel. In conclusion, SARS-CoV-2 RNA could play as sponge of host miRNA to disturb cell growth and cytokine signaling. It suggests an important clue for designing COVID-19 drug and vaccine.
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COVID-19 , MicroRNAs , Regiões 3' não Traduzidas , COVID-19/genética , Proliferação de Células , Citocinas/genética , Humanos , Interleucina-6/genética , Luciferases/genética , MicroRNAs/metabolismo , RNA Viral , SARS-CoV-2 , Fator de Necrose Tumoral alfa/genéticaRESUMO
miR-34a targeting on Smad4 plays important role in TGF-ß1 pathway which is a dominant factor for balancing collagen production and degradation in hepatic stellate cells. TGF-ß1/Smad4 regulated collagen deposition is a hallmark of hepatic fibrosis. The potential regulation on miR-34a by LncRNAs in hepatic stellate cells (HSCs) is still reserved to be revealed. In current study, it was hypothesized that a miR-34a interactor, lncRNA CCAT2 may regulate TGF-ß1 pathway in liver fibrotic remodeling. The interaction between CCAT2 and miR-34a-5p was checked by dual luciferase assay. the effects of CCAT2 and miR-34a-5p on cell proliferation and apoptosis were verified by MTT assay, colony formation assay, and flow cytometry assay. Dual luciferase activity showed CCAT2 are targets of miR-34a-5p. Sh-CCAT2 transfection prohibit HSCs proliferation and induce HSCs apoptosis, also inhibited ECM protein synthesis in HSCs. Decreased miR-34a-5p enhanced HSCs proliferation, blocked HSCs apoptosis and promoted ECM protein production. miR-34a-5p inhibitor undo protective regulation of sh-CCAT2 in liver fibrosis. Furthermore, clinical investigation showed that CCAT2 and Smad4 expression level were significantly induced, while miR-34a-5p was significantly decreased in HBV related liver fibrosis serum. In conclusion, activated HSCs via TGF-ß1/Smad4 signaling pathway was successfully alleviated by CCAT2 inhibition through miR-34a-5p elevation.
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Células Estreladas do Fígado , MicroRNAs , RNA Longo não Codificante , Proteína Smad4 , Fator de Crescimento Transformador beta1 , Humanos , Proliferação de Células/genética , Colágeno , Cirrose Hepática/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Proteína Smad4/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(Pï¼0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (Pï¼0.05); the level of LVP+dP/dtmax was decreased (Pï¼0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (Pï¼0.05 or Pï¼0.01), while the level of glucose was increased (Pï¼0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.
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Antirretrovirais , Cardiotoxicidade , Miócitos Cardíacos , Animais , Antirretrovirais/efeitos adversos , Peso Corporal , Colágeno , Feminino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/ultraestrutura , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Traditional pathogenic diagnosis presents defects such as a low positivity rate, inability to identify uncultured microorganisms, and time-consuming nature. Clinical metagenomics next-generation sequencing can be used to detect any pathogen, compensating for the shortcomings of traditional pathogenic diagnosis. We report third-generation long-read sequencing results and second-generation short-read sequencing results for ascitic fluid from a patient with liver ascites and compared the two types of sequencing results with the results of traditional clinical microbial culture. The distribution of pathogenic microbial species revealed by the two types of sequencing results was quite different, and the third-generation sequencing results were consistent with the results of traditional microbial culture, which can effectively guide subsequent treatment. Short reads, the lack of amplification, and enrichment to amplify signals from trace pathogens, and host background noise may be the reasons for the high error in the second-generation short-read sequencing results. Therefore, we propose that long-read-based rRNA analysis technology is superior to the short-read shotgun-based metagenomics method in the identification of pathogenic bacteria.
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Ascite/genética , Infecções Bacterianas/genética , RNA Ribossômico/genética , Bactérias/patogenicidade , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenômica/métodos , Análise de Sequência de DNA/métodosRESUMO
Biomarkers are critical for rapid diagnosis of tuberculosis (TB) and could benefit patients with AIDS where diagnosis of TB co-infection is challenging. Meta-analysis is an approach to combine the results of the studies with standard statistical method by weighting each study with different sample size. This study aimed to use meta-analysis to integrate transcriptome datasets from different studies and screen for TB biomarkers in patients who were HIV-positive. Five datasets were subjected to meta-analysis on whole-blood transcriptomes from 640 patients infected with HIV. A total of 293 differentially expressed genes (DEGs) were identified as significant (P<0.0001) using the random effective model to integrate the statistical results from each study. DEGs were enriched in biological processes related to TB, such as "Type I interferon signaling" and "stimulatory C-type lectin receptor signaling". Eighteen DEGs had at least a two-fold change in expression between patients infected with HIV who were TB-positive and those who were TB-negative. GBP4, SERPING1, ATF3 and CDKBN3 were selected as a biomarker panel to perform multivariable logistic regression analysis on TB status and relative gene expression levels. The biomarker panel showed excellent accuracy (AUC>0.90 for HIV+TB) in clinical trial and suggests that meta-analysis is an efficient method to integrate transcriptome datasets from different studies.
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Coinfecção , Infecções por HIV , Tuberculose , Biomarcadores , Infecções por HIV/complicações , Humanos , Transcriptoma , Tuberculose/complicações , Tuberculose/diagnósticoRESUMO
BACKGROUND: With the widespread use of integrase strand transfer inhibitors (INSTIs) in the clinical setting, transmission of INSTIs-resistance mutations may increase. Data regarding transmitted drug resistance mutations (TDRM) to INSTIs in Chinese HIV patients are limited. The aim of this study was to summarize the INSTIs TDRM, including the frequency of protease inhibitors (PIs) and reverse transcriptase (RT) inhibitors (RTIs) mutations in treatment-naïve patients in Southeast China. METHODS: HIV-1 positive patients were retrospectively selected between April 2018 and October 2020 from the Mengchao Hepatobiliary Hospital of Fujian Medical University, the largest designated HIV/AIDS care hospital in Southeast China. Individuals who were antiretroviral therapy-naïve and received antiretroviral drug resistance testing at baseline were included. Clinical data including demographic data, CD4 counts, HIV-RNA loads, and drug resistance mutations were collected. RESULTS: A total of 147 patients were enrolled. INSTIs TDRM was rare, with only one primary integrase mutation E138K observed in one sample and one secondary mutation E157Q detected in another sample. The overall prevalence of INSTIs TDRM was 1.36%. A substantial proportion of patients harbored common INSTIs-associated polymorphic variants. Two samples harbored the T215S, M184V and K70E mutations related to nucleoside RTIs (NRTIs). Twelve patients carried nonnucleoside RTIs (NNRTIs)-resistance mutations. Two individuals harbored PIs-resistance mutations: Q58E in one patient and M46I, I54V, V82A, L10F, and Q58E mutations in another patient. The total TDRM rate for RTIs and PIs was 10.20% (15/147), but only 0.68% (1/147) was according to the WHO recommendations on TDRM. CONCLUSION: The rate of INSTIs TDRM was low among therapy-naïve HIV patients in Southeast China. INSTIs as a first-line regimen are suitable for untreated HIV-1 patients in Southeast China. But special attention must be still paid to INSTIs TDRM in clinical practice.
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Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Relação Dose-Resposta a Droga , Feminino , Infecções por HIV/metabolismo , Inibidores de Integrase de HIV/química , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Relação Estrutura-Atividade , Adulto JovemRESUMO
In coronavirus disease 2019 (COVID-19) patients, interleukin (IL)-6 is one of the leading factors causing death through cytokine release syndrome. Hence, identification of IL-6 downstream from clinical patients' transcriptome is very valid for analyses of its mechanism. However, clinical study is conditional and time consuming to collect optional size of samples, as patients have the clinical heterogeneity. A possible solution is to deeply mine the relative existing data. Several transcriptome-based studies on other diseases or treatments have revealed different genes to be regulated by IL-6. Through our meta-analysis of these transcriptome datasets, 352 genes were suggested to be regulated by IL-6 in different biological conditions, some of which were related to virus infection and cardiovascular disease. Among them, 232 genes were not identified by current transcriptome studies from clinical research. ICAM1 and PFKFB3 were the most significantly upregulated genes in our meta-analysis and could be employed as biomarkers in patients with severe COVID-19. In general, a meta-analysis of transcriptome datasets could be an alternative way to analyze the immune response and complications of patients suffering from severe COVID-19 and other emergency diseases.
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OBJECTIVES: Determine if different DC-SIGNR genotypes/alleles correlated with HIV susceptibility in the context of the HIV mode of infection, CD4+ T cell counts and blood HIV RNA loads. METHODS: One hundred forty-five HIV infected individuals and 187 uninfected healthy controls were recruited to observe whether DC-SIGNR genotypes/alleles were correlated with HIV susceptibility, CD4+ T cell numbers and HIV-RNA levels. RESULTS: The frequencies of DC-SIGNR genotypes/alleles in HIV-infected patients were similar to those seen in the uninfected population. However, the 9-repeat DCSIGNR allele was more frequently found in patients infected via sexual transmission compared to patients infected via blood transmission/intravenous drug use (p = 0.005). HIV RNA levels in patients with the 9- or 7-repeat DC SIGNR allele were significantly higher than the levels observed in patients with the 5-repeat DC SIGNR allele (p = 0.004, p = 0.004, respectively) and the HIV RNA levels in patients with the 9/7 genotype or with the 7/7 genotype were significantly higher than patients with the 7/5 genotype (p = 0.003, p = 0.029, respectively). There were no significant differences between CD4+ T cells in patients with different DC-SIGNR genotypes/alleles. CONCLUSIONS: No DC-SIGNR genotypes/alleles were associated with reduced HIV susceptibility, however, DC-SIGNR genotypes/alleles with higher repeat numbers were associated with higher HIV-RNA blood levels, that is, the 9-repeat DC-SIGNR allele was significantly associated with increased HIV-RNA levels and HIV sexual transmission.
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Moléculas de Adesão Celular/genética , HIV/genética , HIV/imunologia , Lectinas Tipo C/genética , RNA Viral/análise , Receptores de Superfície Celular/genética , Sequências Repetitivas de Ácido Nucleico/genética , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , Moléculas de Adesão Celular/metabolismo , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV , Humanos , Lactente , Lectinas Tipo C/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Isoformas de Proteínas/genética , Receptores de Superfície Celular/metabolismo , Doenças Virais Sexualmente Transmissíveis , Carga Viral , Virulência/genéticaRESUMO
A kind of "intelligent" antibacterial dressing-A-HA/HA-ADH/SS hydrogel was in situ formed quickly via dynamic covalent bonds cross-linking between aldehyde hyaluronic acid (A-HA), adipic acid dihydrazide graft hyaluronic acid (HA-ADH) and sisomicin sulfate (SS). FT-IR, SEM and rheological results displayed that the hydrogels were successfully prepared. The hydrogels had good optical transmittance, injectability, self-healing ability, cytocompatibility, antioxidant activity and hemostatic performance which were beneficial to observe the wound healing condition and provide a good healing environment for wounds. In addition, the hydrogels showed a pH- and HAase- dependent degradability, which allowed them to release more SS at infected wound and then exert on-demand and sustained antibacterial effect against S. aureus and E. coli. The results of wound healing and histological examination revealed that these hydrogels have a good therapeutic effect in the full-thickness mouse skin defect wound. Thus, the hydrogels are expected to be used as potential wound dressings to improve wound healing.
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Antibacterianos , Escherichia coli/crescimento & desenvolvimento , Hidrogéis , Sisomicina , Staphylococcus aureus/crescimento & desenvolvimento , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Linhagem Celular , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos BALB C , Sisomicina/química , Sisomicina/farmacocinética , Sisomicina/farmacologiaRESUMO
Tolllike receptor 2 (TLR2), is an important pattern recognition receptor which serves a role in chronic inflammation of the liver. However, the role of TLR2 in the progression of human hepatocellular carcinoma (HCC) remains unknown. The aim of the present study was to examine the effects of the activation of the TLR2 signaling pathway on biological functions, such as proliferation and apoptosis. TLR2 expression in HCC tissues was assayed by quantitative polymerase chain reaction, flow cytometry and western blotting. B76/Huh7 cells were transfected with overexpression plasmids, and cell proliferation was detected using a Cell Counting Kit8 assay and the secreted cytokines in the supernatant of transfected cells were measured by ELISA. The findings revealed that TLR2 expression was increased in the peritumoral groups compared with innertumoral groups. Activation of the TLR2 signaling pathway through overexpression of pathway molecules inhibited the growth of B76/Huh7 cells and the secretion of interleukin6 and tumor necrosis factorα were reduced. Inhibition of the TLR2 signaling pathway resulted in a significant increase in the downstream signaling cascade, thus potentially increasing hepatocarcinogenesis and tumor progression. Activation of the TLR2 signaling pathway may be a potential target for therapeutic intervention in patients with HCC and downstream secreted cytokines are required for the functional biological effect. Therefore, modulation of the TLR2 signaling pathway may provide important insight into designing effective therapeutic regimens for treating patients with HCC.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células , Neoplasias Hepáticas/patologia , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 2 Toll-Like/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas In Vitro , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Prognóstico , Transdução de Sinais , Receptor 2 Toll-Like/genética , Células Tumorais CultivadasRESUMO
Dengue fever (DF) could develop into dengue haemorrhagic fever (DHF) with increased mortality rate. Since the clinical characteristics and pathogen are same in DF and DHF. It's important to identify different molecular biomarkers to predict DHF patients from DF. We conducted a clinical plasma proteomics study using quantification (TMT)-based quantitative proteomics methodology to found the differential expressed protein in DF patients before they developed into DHF. In total 441 proteins were identified up or down regulated. There proteins are enriched in diverse biological processes such as proteasome pathway, Alanine, aspartate, and glutamate metabolism and arginine biosynthesis. Several proteins such as PLAT, LAMB2, and F9 were upregulated in only DF patients which developed into DHF cases, not in DF, compared with healthy-control. In another way, FGL1, MFAP4, GLUL, and VCAM1 were upregulated in both DHF and DF cases compare with healthy-control. RT-PCR and ELISA were used to validate these upregulated gene expression and protein level in 54 individuals. Results displayed the same pattern as proteomics analysis. All including PLAT, LAMB2, F9, VCAM1, FGL1, MFAP4, and GLUL could be considered as potential markers of predicting DHF since the levels of these proteins vary between DF and DHF. These new founding identified potential molecular biomarkers for future development in precision prediction of DHF in DF patients.
RESUMO
OBJECTIVES: Pseudomonas aeruginosa is a common Gram-negative bacterium causing various serious infections, such as lower respiratory tract infection and urinary tract infection in catheterised patients. Here we report the draft genome sequence of a carbapenem-resistant P. aeruginosa (CRPA) isolate. METHODS: The genome of the CRPA isolate was sequenced using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. RESULTS: The resulting assembly was highly contiguous, containing a total of 6624003bp with a GC content of 66.21%. Annotation identified 6389 protein-coding genes. Mutations in the oprD and mexR genes conferred resistance to carbapenems in the CRPA isolate. CONCLUSION: The draft genome sequence of this CRPA isolate could provide a solid basis for further research on the resistance mechanisms and the development of drug therapy for drug resistance genes.