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1.
Ann Hepatol ; 29(4): 101475, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38331384

RESUMO

INTRODUCTION AND OBJECTIVES: Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria and release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) is a sensor that induces cell death. Here, we investigated whether ZBP1 participates in hepatocyte pyroptosis and explored the possible pathogenesis of ALI. MATERIALS AND METHODS: Hepatocyte pyrotosis was induced with lipopolysaccharide (LPS) and nigericin (Nig), and the expression of Zbp1 (ZBP1) was examined by western blot analysis and RT-qPCR. Further, we transfected AML-12 (LO2 and HepG2) cell lines with Zbp1 (ZBP1) siRNA. After ZBP1 was silenced, LDH release and flow cytometry were used to measure the cell death; Western blot analysis and RT-qPCR were used to detect the marker of NLRP3 inflammasome activation and pyroptosis. We also detected the expression of mitochondrial linear rupture marker phosphoglycerate mutase family member 5 (PGAM5) using western blot analysis and reactive oxygen species (ROS) using the DCFH-DA method. RESULTS: The expression of ZBP1 was up-regulated in LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited NLRP3 inflammasome activation and pyroptosis in LPS/Nig-induced hepatocytes. Moreover, ZBP1 silencing inhibited the expression of PGAM5 by reducing ROS production. CONCLUSIONS: ZBP1 promotes hepatocellular pyroptosis by modulating mitochondrial damage, which facilitates the extracellular release of ROS.

2.
BMC Gastroenterol ; 23(1): 387, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951866

RESUMO

BACKGROUND: The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15 - 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in better managing mothers with hepatitis B. We aim to assess the frequency of postpartum ALT flares and predictors for such events. METHOD: This study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infection (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted to prevent Mother-to-child transmission (MTCT) but discontinued at delivery if there is no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12-24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary objective is the proportion of patients with postpartum ALT flares. The secondary objectives are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. DISCUSSION: The current study focuses on the incidence of postpartum ALT flares in mothers with chronic hepatitis B including subgroup analysis based on HBeAg status. The data will have several clinical implications, such as providing evidence for an appropriate monitoring schedule in CHB mothers after delivery. Further analyses on predictors of such events may assist clinicians in identifying mothers who might develop severe postpartum ALT flares. The data generated from healthy mothers have the potential to identify the patterns of ALT changes during pregnancy and postpartum, so we can gain a better understanding of the normal range of ALT in this subpopulation. TRIAL REGISTRATION NUMBER AT THE CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2200061130.


Assuntos
Hepatite B Crônica , Lactente , Gravidez , Humanos , Feminino , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/tratamento farmacológico , Estudos Prospectivos , Alanina Transaminase , Antivirais/uso terapêutico , Antígenos E da Hepatite B , Estudos de Coortes , Incidência , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Período Pós-Parto , Vírus da Hepatite B/genética , DNA Viral
3.
Front Immunol ; 14: 1279264, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954583

RESUMO

Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body's immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions. Macrophage polarization can occur in two directions: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. Controlling the ratio and direction of M1 and M2 in ALF can help reduce liver injury. However, the liver damage caused by pyroptosis should not be underestimated, as it is a caspase-dependent form of cell death. Inhibiting pyroptosis has been shown to effectively reduce liver damage induced by ALF. Furthermore, macrophage polarization and pyroptosis share common binding sites, signaling pathways, and outcomes. In the review, we describe the role of macrophage polarization and pyroptosis in the pathogenesis of ALF. Additionally, we preliminarily explore the relationship between macrophage polarization and pyroptosis, as well as their effects on ALF.


Assuntos
Falência Hepática Aguda , Piroptose , Humanos , Hepatócitos/metabolismo , Falência Hepática Aguda/patologia , Células de Kupffer , Macrófagos
5.
J Int Med Res ; 51(10): 3000605231204430, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37890141

RESUMO

Scrub typhus (ST) is an acute focal infectious disease that is caused by Orientia tsutsugamushi. The Asia-Pacific region is an area of relatively high incidence. There is a high incidence in China, principally owing to the disease being endemic in the south of the country. The main source of ST infection is rats, which act as reservoirs of infection after being bitten by the chigger mite, and the human population is generally susceptible to the disease. ST can be controlled and treated successfully if antibiotics are administered in a timely manner. However, because it does not have a specific clinical manifestation, it is difficult to distinguish ST from other febrile diseases in clinical practice. Therefore, rapid diagnostic methods are still needed to help clinicians make a timely diagnosis. Here, we share three cases of patients with ST who experienced hemorrhage, but did not have typical skin lesions, such as eschar and ulcer, early in the course of their disease, and review the relevant literature regarding ST. We conclude that clinicians should pay attention to the risk of hemorrhage associated with this disease, and emphasize the importance of making an early diagnosis.


Assuntos
Orientia tsutsugamushi , Tifo por Ácaros , Doenças Vasculares , Humanos , Animais , Ratos , Tifo por Ácaros/complicações , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/tratamento farmacológico , Hemorragia/complicações , Ásia , Doenças Vasculares/complicações
6.
Front Med ; 17(5): 957-971, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37314648

RESUMO

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.


Assuntos
Transtornos da Motilidade Ciliar , Sêmen , Humanos , Masculino , Animais , Camundongos , Sêmen/metabolismo , Dineínas/genética , Dineínas/metabolismo , Cílios/genética , Cílios/metabolismo , Mutação , Transtornos da Motilidade Ciliar/genética
7.
Eur J Med Res ; 28(1): 76, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782344

RESUMO

BACKGROUND: Cerebral malaria (CM) is a manifestation of malaria caused by plasmodium infection. It has a high mortality rate and severe neurological sequelae, existing a significant research gap and requiring further study at the molecular level. METHODS: We downloaded the GSE117613 dataset from the Gene Expression Omnibus (GEO) database to determine the differentially expressed genes (DEGs) between the CM group and the control group. Weighted gene coexpression network analysis (WGCNA) was applied to select the module and hub genes most relevant to CM. The common genes of the key module and DEGs were selected to perform further analysis. The least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) were applied to screen and verify the diagnostic markers of CM. Eventually, the hub genes were validated in the external dataset. Gene set enrichment analysis (GSEA) was applied to investigate the possible roles of the hub genes. RESULTS: The GO and KEGG results showed that DEGs were enriched in some neutrophil-mediated pathways and associated with some lumen structures. Combining LASSO and the SVM-RFE algorithms, LEF1 and IRAK3 were identified as potential hub genes in CM. Through the GSEA enrichment results, we found that LEF1 and IRAK3 participated in maintaining the integrity of the blood-brain barrier (BBB), which contributed to improving the prognosis of CM. CONCLUSIONS: This study may help illustrate the pathophysiology of CM at the molecular level. LEF1 and IRAK3 can be used as diagnostic biomarkers, providing new insight into the diagnosis and prognosis prediction in pediatric CM.


Assuntos
Malária Cerebral , Criança , Humanos , Malária Cerebral/diagnóstico , Malária Cerebral/genética , África , Algoritmos , Aprendizado de Máquina , Biomarcadores
8.
Front Cardiovasc Med ; 9: 839166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35449877

RESUMO

Background: Drug exposure during gestation or in prematurely born children represents a significant risk to congenital heart disease (CHD). Amantadine is an antiviral agent also effective in the treatment of Parkinson's disease. However, while its potential side effects associated with tetralogy of fallot (ToF) and birth defects were implicated, its underlying etiologic mechanisms of action remain unknown. Here, we report teratogenic effects of amantadine drug during early cardiogenesis through developing a novel zebrafish (Danio rerio) knock-in (KI) animal model and explore the underlying mechanisms. Methods: Homologous recombination (HR) pathway triggered by CRISPR/Cas9 system was utilized to generate an enhanced green fluorescent protein (EGFP) KI zebrafish animal model. Dynamic fluorescence imaging coupled with a whole-mount in-situ hybridization (WISH) assay was employed to compare the spatial and temporal expression patterns of the EGFP reporter in the KI animal model with the KI-targeted endogenous gene. Heart morphology and EGFP expression dynamics in the KI animal models were monitored to assess cardiac side effects of different doses of amantadine hydrochloride. Expression of key genes required for myocardium differentiation and left-right (LR) asymmetry was analyzed using WISH and quantitative reverse transcription-PCR (RT-PCR). Results: A novel EGFP KI line targeted at the ventricular myosin heavy chain (vmhc) gene locus was successfully generated, in which EGFP reporter could faithfully recapitulate the endogenous expression dynamics of the ventricle chamber-specific expression of the vmhc gene. Amantadine drug treatment-induced ectopic expression of vmhc gene in the atrium and caused cardiac-looping or LR asymmetry defects to dose-dependently during early cardiogenesis, concomitant with dramatically reduced expression levels of key genes required for myocardium differentiation and LR asymmetry. Conclusion: We generated a novel zebrafish KI animal model in which EGFP reports the ventricle chamber-specific expression of vmhc gene dynamics that is useful to effectively assess drug safety on the cardiac morphology in vivo. Specifically, this study identified teratogenic effects of amantadine drug during early cardiogenesis dose dependent, which could be likely conveyed by inhibiting expression of key genes required for cardiac myocardium differentiation and LR asymmetry.

9.
Jpn J Infect Dis ; 75(2): 183-191, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-34053954

RESUMO

Xpert Xpress Flu/RSV is a fast and automated real-time nucleic acid amplification tool for detecting influenza virus and respiratory syncytial virus (RSV). The aim of this study was to verify the accuracy of Xpert Xpress Flu/RSV for detecting influenza virus and RSV. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched up to October 2020. The quality of the original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 guidelines. Meta-DiSc 1.4 software was used to analyze the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve. Deek's funnel plot asymmetry test was used to evaluate the publication bias using the Stata 12.0 software. Ten studies with 25 fourfold tables were included in the analysis. The sensitivity of Xpert Xpress Flu/RSV for detecting influenza A, influenza B, and RSV were 0.97, 0.98, and 0.96, respectively, and the specificities were 0.97, 1.00, and 1.00, respectively. Compared with other common clinical real-time reverse transcription-polymerase chain reaction (RT-PCR), Xpert Xpress Flu/RSV is a valuable tool for diagnosing influenza virus and RSV with high sensitivity and specificity.


Assuntos
Vírus da Influenza A , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Técnicas de Diagnóstico Molecular , Nasofaringe , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/genética , Sensibilidade e Especificidade
10.
Turk J Gastroenterol ; 32(10): 896-906, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34787095

RESUMO

BACKGROUND: To date, studies have shown inconsistent results of treatment with bone marrow-derived stem cells (BMDSC) for patients with liver cirrhosis. This study aims to compare the efficacy and safety of BMDSC and standard therapy for liver cirrhosis. METHODS: Articles from PubMed, Embase, and the Cochrane library were searched from inception to April 2018. The index included Model for End-stage Liver Disease (MELD), alanine aminotransferase (ALT), albumin, total bilirubin (TBIL), prothrombin time (PT), Child-Pugh score, and all-cause mortality. RESULTS: A total of 9 studies with a total of 424 patients with liver cirrhosis were included in final meta-analysis. BMDSC therapy was associated with lower MELD within 3 months (P = .010), while it had no significant impact on MELD after 6 months (P = .074). There were no differences between BMDSC and standard therapy for ALT within 3 months (P = .336) and after 6 months (P = .379). BMDSC did not affect albumin level within 3 months (P = .196) and after 6 months (P = .840). BMDSC reduced the TBIL level within 3 months (P = .037) and was not associated with the TBIL level after 6 months (P = .914). There were no differences between BMDSC and standard therapy for PT within 3 months (P = .167) and after 6 months (P = .484). The Child-Pugh scores within 3 months (P = .342) and after 6 months (P = .133) were not associated with BMDSC treatment for liver cirrhosis patients. Finally, the BMDSC was not associated with the risk of all-cause mortality, as compared with standard therapy (P = .622). CONCLUSIONS: BMDSC treatment for patients with liver cirrhosis could improve short-term MELD and TBIL, but not the risk of mortality, as compared with standard therapy.


Assuntos
Células da Medula Óssea , Cirrose Hepática , Transplante de Células-Tronco , Humanos , Cirrose Hepática/terapia
11.
Virol J ; 18(1): 121, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108015

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.


Assuntos
COVID-19/complicações , Hepatopatias/etiologia , SARS-CoV-2 , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Humanos , Incidência , Hepatopatias/diagnóstico , Hepatopatias/terapia , Masculino , Medicina Tradicional Chinesa/efeitos adversos
12.
Biomed Res Int ; 2020: 2892734, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102576

RESUMO

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely spread across the world. Asymptomatic or inconspicuous CT/NG infections are difficult to diagnose and treat. Traditional methods have the disadvantages of low detection rate, inaccurate results, and long detection time. However, Xpert CT/NG makes up for the aforementioned shortcomings and has research value and popularization significance. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched, and studies were screened using Xpert CT/NG for diagnosing CT/NG. QUADAS-2 was used to evaluate the quality of the eligible studies. Then, two groups of researchers independently extracted data from these studies. Meta-analyses of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were conducted using Meta-DiSc 1.4. Finally, Deek's funnel plots were made using Stata 12.0 to evaluate publication bias. RESULTS: 14 studies were identified, and 46 fourfold tables were extracted in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing CT were 0.94 (95% confidence interval (CI): 0.93-0.95), 0.99 (95% CI: 0.99-1.00), 97.17 (95% CI: 56.76-166.32), 0.07 (95% CI: 0.04-0.12), 1857.25 (95% CI: 943.78-3654.86), and 0.9960, respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing NG were 0.95 (95% CI: 0.93-0.96), 1.00 (95% CI: 1.00-1.00), 278.15 (95% CI: 152.41-507.63), 0.08 (95% CI: 0.06-0.12), 4290.70 (95% CI: 2161.78-8516.16), and 0.9980, respectively. CONCLUSIONS: Xpert CT/NG had high diagnostic sensitivity and specificity for CT and NG. However, more evidence is required to confirm that Xpert CT/NG might serve as the primary method for detecting CT and NG and even the gold standard for diagnosis in the future.


Assuntos
Infecções por Chlamydia/diagnóstico , Gonorreia/diagnóstico , Área Sob a Curva , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Gonorreia/microbiologia , Humanos , Neisseria gonorrhoeae/patogenicidade , Razão de Chances , Curva ROC , Sensibilidade e Especificidade
13.
Artigo em Inglês | MEDLINE | ID: mdl-32876296

RESUMO

The consequences of COVID-19 infecting pregnant women and the potential risks of vertical transmission have become a major issue. Since little is currently known about COVID-19 in pregnancy, the understanding of COVID-19 in this particular group will be updated in time, and a comprehensive review will be useful to evaluate the impact of COVID-19 in pregnancy. Based on recently published literature and official documents, this review provides an introduction to the pathogenesis, pathology, and clinical features of COVID-19 and has focused on the current researches on clinical features, pregnancy outcomes and placental histopathological analysis from pregnant women infected with SARS-CoV-2 in comparison with SARS-CoV and MERS-CoV. These viruses trigger a cytokine storm in the body, produce a series of immune responses, and cause changes in peripheral leukocytes and immune system cells leading to pregnancy complications that may be associated with viral infections. The expression of ACE2 receptors in the vascular endothelium may explain the histological changes of placentas from pregnant women infected by SARS-CoV-2. Pregnant women with COVID-19 pneumonia show similar clinical characteristics compared with non-pregnant counterparts. Although there is no unequivocal evidence to support the fetal infection by intrauterine vertical transmission of SARS, MERS and SARS-CoV-2 so far, more and more articles began to report maternal deaths due to COVID-19. In particular, from February 26, 2020 (date of the first COVID-19 case reported in Brazil) until June 18, 2020, Brazil reported 124 maternal deaths. Therefore, pregnant women and neonates require special attention regarding the prevention, diagnosis and management of COVID-19.


Assuntos
Betacoronavirus , Pneumonia Viral , Complicações Infecciosas na Gravidez/virologia , Brasil , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Recém-Nascido , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Gravidez , SARS-CoV-2
14.
BMC Infect Dis ; 20(1): 560, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736603

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

15.
BMC Infect Dis ; 20(1): 525, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689953

RESUMO

BACKGROUND: Neisseria meningitidis is a major cause of bacterial meningitis, and these infections are associated with a high mortality rate. Rapid and reliable diagnosis of bacterial meningitis is critical in clinical practice. However, this disease often occurs in economically depressed areas, so an inexpensive, easy to use, and accurate technology is needed. We performed a pooled-analysis to assess the potential of the recently developed loop-mediated isothermal amplification (LAMP) assay for detection of meningococcus. METHODS: Pubmed, Embase, and Web of Science were searched to identify original studies that used the LAMP assay to detect meningococcus. After pooling of data, the sensitivity and specificity were calculated, a summary receiver operating characteristic (SROC) curve was determined, and the area under the SROC curve was computed to determine diagnostic accuracy. Publication bias was assessed using Deek's funnel plot. RESULTS: We examined 14 studies within 6 publications. The LAMP assay had high sensitivity (94%) and specificity (100%) in the detection of meningococcus in all studies. The area under the SROC curve (0.980) indicated high overall accuracy of the LAMP assay. There was no evidence of publication bias. DISCUSSION: The LAMP assay has accuracy comparable to bacterial culture and PCR for detection of meningococcus, but is less expensive and easier to use. We suggest the adoption of the LAMP assay to detect meningococcus, especially in economically depressed areas.


Assuntos
Meningite Meningocócica/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neisseria meningitidis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Confiabilidade dos Dados , Humanos , Meningite Meningocócica/microbiologia , Técnicas de Diagnóstico Molecular/economia , Técnicas de Amplificação de Ácido Nucleico/economia , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Curva ROC , Sensibilidade e Especificidade
16.
BMC Microbiol ; 20(1): 179, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576134

RESUMO

BACKGROUND: Streptococcus agalactiae (GBS) is the causative pathogen of puerperal sepsis in pregnant women and pneumonia, sepsis and meningitis in infants. Infection of GBS is responsible for the increased morbidity in pregnant women and the elderly, and bring challenges to clinical diagnosis and treatment. However, culture-based approaches to detect S.agalactiae is time-consuming with limited sensitivity. Besides, real-time quantitative PCR demands expensive instruments with tedious steps. Thus, we aim to establish a new detection method for more accurate and rapid detection of S.agalactiae. RESULTS: The ddPCR primer targeted the CpsE gene showed better amplified efficiency in the reaction. The limit of detection for GBS DNA with ddPCR was able to reach 5 pg/µL. Moreover, no positive amplified signals could be detected in the reactions which served 11 non-GBS strains DNA as templates. Furthermore, the coefficient of variation of this method was 4.5%, indicating excellent repeatability of ddPCR assay. CONCLUSIONS: In our study, ddPCR was performed as a rapid detection of S.agalactiae with high sensitivity and specificity. This technique can promote the accuracy of the diagnosis of GBS infection and provide a scientific basis for clinical treatment.


Assuntos
Proteínas de Bactérias/genética , Reação em Cadeia da Polimerase/métodos , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Primers do DNA/genética , Diagnóstico Precoce , Humanos , Limite de Detecção , Streptococcus agalactiae/genética
17.
J Enzyme Inhib Med Chem ; 35(1): 1224-1232, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32420773

RESUMO

Novel antibacterial agents are urgently needed to address the infections caused by multi-drug resistant bacteria. Urinary tract infections are common infectious diseases in clinical. Most of these infections are caused by drug-resistant uropathogenic Escherichia coli. PPK1 is an essential kinase for bacterial motility, biofilm formation, quorum sensing, and virulence factors in the expression of uropathogenic E. coli. In the present study, two small molecules potentially targeting PPK1 were discovered through virtual screening and biological assays. The in vitro and in vivo results suggested that the interaction of these compounds with PPK1 can disrupt biofilm formation of uropathogenic E. coli and reduce invasive ability and resistance to oxidative stress of this strain. Moreover, the compounds exhibit good antibacterial bacterial activity in the mice with urinary tract infection. Taken together, our findings could provide a new chemotype for the development of antibacterials targeting PPK1.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas , Proteínas Quinases/metabolismo , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/efeitos dos fármacos , Antibacterianos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Humanos , Infecções Urinárias/microbiologia
18.
J Clin Lab Anal ; 34(7): e23281, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32157743

RESUMO

BACKGROUND: Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop-mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically. METHODS: Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS-2 tool independently. I2 statistic and chi-square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection. RESULTS: A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies. CONCLUSION: Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection.


Assuntos
Hepatite B/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Hepatite B/sangue , Humanos , Controle de Qualidade , Sensibilidade e Especificidade
19.
Biosci Rep ; 39(10)2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31537628

RESUMO

BACKGROUND: Candida is a fungus that causes various types of candidemia, which is the fourth major infectious disease of the blood system. MALDI-TOF-MS is a simple and rapid detection instrument. The aim of the present study was to verify the accuracy of MALDI-TOF-MS in detecting Candida. METHOD: A pooled analysis of articles on MALDI-TOF-MS for diagnosis of candidemia was performed. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Stata 12.0 software was used to merge the correct identification rates of Candida and Candida subspecies and obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity was found in the subgroup analysis of the included articles. Hence, we explored the factors causing the heterogeneity and its impact on the overall situation. Sensitivity analysis was used to examine the effect of Candida level on total response. Egger's test was used to evaluate the publication bias of the included articles. RESULTS: A total of 16 articles in Pubmed, 79 articles in Embase, 1 article in Cochrane Library, 30 articles in Web of Science and 3 from other sources were identified, of which 10 articles were included based on the inclusion and exclusion criteria. The overall identification accuracy was 100%. CONCLUSION: The accuracy of MALDI-TOF-MS for the identification of Candida was 100%. Further research is necessary to determine whether MALDI-TOF-MS can be used as a clinical diagnostic standard for the identification of Candida.


Assuntos
Candida/metabolismo , Candidíase/diagnóstico , Candidíase/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/classificação , Candida/classificação , Humanos
20.
Biochem Biophys Res Commun ; 499(2): 120-127, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29481800

RESUMO

The present study was to investigate clinical significance, biological functions and underlying mechanisms of BTB Domain and CNC Homolog 1(BACH1) deregulation in human colorectal cancer (CRC). The result showed that BACH1 upregulation was significantly associated with enhanced tumor invasion (P = 0.014) and gender (P = 0.028) of CRC patients. Kaplan-Meier method results showed that the overall survival of CRC patients with high BACH1 mRNA expression was markedly shorter than those with low expression (P = 0.015), and multivariate analyzes results showed that BACH1 was an independent prognostic predictor for CRC patients (P = 0.049). In vitro studies revealed that BACH1 efficiently promoted invasion and migration of CRC cell line. In vitro studies proved that the HCT116 cell stably expressing BACH1 formed significantly larger tumor nodules and remarkably accelerated tumor xenografts growth. In addition, Immunohistochemical scores of CD31 and Vimentin were significantly higher than those of the control group. Finally, correlation analysis indicated that BACH1 expression was positively correlated with C-X-C Motif Chemokine Receptor 4(CXCR4) in tumor tissues and cell lines. Together, BACH1 serves as an oncogene to promote CRC progression and an independent prognostic factor for survival and metastasis. BACH1 may inhibit the progression of CRC through BACH1/CXCR4 pathway.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Receptores CXCR4/metabolismo , Transdução de Sinais , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CXCR4/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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