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1.
Urol J ; 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733232

ABSTRACT

BACKGROUND: Our study aims to address two pivotal questions: "What are the recent advancements in understanding the etiology of urological tumors through Mendelian Randomization?" and "How can Mendelian Randomization be more effectively applied in clinical settings to enhance patient health outcomes in the future?" METHODS: In our systematic review conducted in April 2023, we utilized databases like PubMed and Web of Science to explore the influence of Mendelian Randomization in urological oncological diseases. We focused on studies published from January 2018, employing keywords related to urological tumors and Mendelian Randomization, supplemented with MeSH terms and manual reference checks. Our inclusion criteria targeted original research studies, while we excluded reports and non-relevant articles.  Data extraction followed a PICO-based approach, and bias risk was independently evaluated, with discrepancies resolved through discussion. This systematic approach adhered to PRISMA guidelines for accuracy and thoroughness in reporting. RESULTS: From the initial 457 publications, we narrowed down to 43 full-text articles after screening and quality assessments.A deeper understanding of Mendelian Randomization can help us explore risk factors with a clear causal relationship to urological tumors.This insight may pave the way for future research in early diagnosis, treatment, and management of associated diseases. CONCLUSION: Our review underscores the value of MR in urogenital tumor research, highlighting its efficacy in establishing causality and its potential to clarify disease mechanisms. Despite challenges like large sample sizes and variant identification, MR offers new perspectives for understanding and managing these tumors, suggesting a trend towards more inclusive and diverse research approaches.

2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014555

ABSTRACT

GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.

3.
Chinese Medical Journal ; (24): 97-104, 2024.
Article in English | WPRIM (Western Pacific) | ID: wpr-1007737

ABSTRACT

BACKGROUND@#The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.@*METHODS@#This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.@*RESULTS@#The optimal cut-off values of L3-SMI were 39.50 cm 2 /m 2 for male patients and 33.06 cm 2 /m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P  = 0.012).@*CONCLUSIONS@#This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.


Subject(s)
Adult , Female , Humans , Male , Leadership , Liver Cirrhosis , Malnutrition/diagnosis , Nutritional Status , Retrospective Studies , Sarcopenia/diagnosis
4.
Genomics ; 115(3): 110634, 2023 05.
Article in English | MEDLINE | ID: mdl-37121446

ABSTRACT

CRKL (CRK Like Proto-Oncogene) belongs to the Crk family and is a 39-kDa adapter protein that encodes SH2 and SH3 (src homologs) domains. To identify its oncogenic role in malignant melanoma, we investigated the association between CRKL and mutation, prognosis, tumor mutation burden, immune cell infiltration of melanoma, and explored the associations between CRKL and immunotherapy response. Our results showed that abnormal CRKL expression is associated with poor prognosis in melanoma and is significantly correlated with immune-activated pathways and processes, immune cell infiltrations, and expression of immunoregulators. Importantly, we found that CRKL expression is a predictive biomarker for anti-PD1 therapy response in melanoma patients. Furthermore, inhibiting CRKL expression in melanoma cell lines suppressed their proliferation and metastasis, as well as activated the pyroptosis-related pathway. Our study provides potential mechanisms of melanoma pathogenesis, which may suggest new avenues for targeted therapy in this disease.


Subject(s)
Melanoma , Nuclear Proteins , Humans , Biomarkers , Immunotherapy , Nuclear Proteins/genetics , Prognosis , Proto-Oncogene Proteins c-crk/metabolism
5.
Article in English | WPRIM (Western Pacific) | ID: wpr-1007892

ABSTRACT

OBJECTIVE@#This study aimed to develop an artificial neural network (ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease (NAFLD) in American adults.@*METHODS@#Data from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) 2007-2014 were analyzed. Eligible subjects ( n = 6,613) were randomly divided into a training set ( n 1 = 4,609) and a validation set ( n 2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.@*RESULTS@#Our study found that the odds ratios ( ORs) and 95% confidence intervals ( CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake (i.e., provitamin A carotenoids, such as β-carotene) ( OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.@*CONCLUSION@#The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.


Subject(s)
Adult , Humans , Vitamin A , Non-alcoholic Fatty Liver Disease/epidemiology , Nutrition Surveys , Diet , Neural Networks, Computer
6.
Neuroscience Bulletin ; (6): 273-291, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-971555

ABSTRACT

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.


Subject(s)
Humans , Tumor Necrosis Factor-alpha , DNA-Binding Proteins/metabolism , Ubiquitin-Specific Peptidase 7 , Cisplatin , Temozolomide , Transcription Factors , Glioma , Cell Proliferation , Melanoma , Cell Line, Tumor , Apoptosis , Nuclear Proteins/genetics
7.
Saudi J Biol Sci ; 29(2): 751-757, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35197741

ABSTRACT

With the progressive focus on renewable energy via biofuels production from lignocellulosic biomass, cellulases are the key enzymes that play a fundamental role in this regard. This study aims to unravel the characteristics of Thermotoga maritima MSB8 (Tma) (a hyperthermophile from hot springs) thermostable glycoside hydrolase enzyme. Here, a glycoside hydrolase gene of Thermotoga maritima (Tma) was heterologously expressed and characterized. The gene was placed in the pQE-30 expression vector under the T5 promotor, and the construct pQE-30-Gh was then successfully integrated into Escherichia coli BL21 (DH5α) genome by transformation. Sequence of the glycoside hydrolase contained an open reading frame of 2.124 kbp, encoded a polypeptide of 721 amino acid residues. The molecular weight of the recombinant protein estimated was 79 kDa. The glycoside hydrolase was purified by Ni+2-NTA affinity chromatography and its enzymatic activity was investigated. The recombinant enzyme is highly stable within an extreme pH range (2.0-7.0) and highly thermostable at 80 °C for 72 h indicating its viability in hyperthermic environment and acidic nature. Moreover, the Ca2+ and Mn2+ introduction stimulated the residual activity of recombinant enzyme. Conclusively, the thermostable glycoside hydrolase possesses potential to be exploited for industrial applications at hyperthermic environment.

8.
Preprint in English | medRxiv | ID: ppmedrxiv-22271138

ABSTRACT

Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants. Here we use systems immunology, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences) from 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19 and 40 age- and sex-matched healthy controls with no history of COVID-19 to comparatively assess the post-infection immune status (mean: 151 days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination. Identification of both sex-specific and -independent temporally stable changes, including signatures of T-cell activation and repression of innate defense/immune receptor genes (e.g., Toll-like receptors) in monocytes, suggest that mild COVID-19 can establish new post-recovery immunological set-points. COVID-19-recovered males had higher innate, influenza-specific plasmablast, and antibody responses after vaccination compared to healthy males and COVID-19-recovered females, partly attributable to elevated pre-vaccination frequencies of a GPR56 expressing CD8+ T-cell subset in male recoverees that are "poised" to produce higher levels of IFN{gamma} upon inflammatory stimulation. Intriguingly, by day 1 post-vaccination in COVID-19-recovered subjects, the expression of the repressed genes in monocytes increased and moved towards the pre-vaccination baseline of healthy controls, suggesting that the acute inflammation induced by vaccination could partly reset the immune states established by mild COVID-19. Our study reveals sex-dimorphic immune imprints and in vivo functional impacts of mild COVID-19 in humans, suggesting that prior COVID-19, and possibly respiratory viral infections in general, could change future responses to vaccination and in turn, vaccines could help reset the immune system after COVID-19, both in an antigen-agnostic manner.

9.
Chinese Pharmacological Bulletin ; (12): 645-649, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014201

ABSTRACT

Excitotoxicity mainly refers to the toxic effect of the excitatory neurotransmitter glutamate.Long-term activation of glutamate receptors will cause a series of neurotoxicity, eventually leading to the loss of neuronal function and cell death.Triggering excitotoxicity may involve changes in glutamate and calcium metabolism, dysfunction of glutamate transporter, N-methyl-D-aspartate receptor(NMDAR)and mitochondria, and production of ROS.Therefore, we here review the occurrence of these mechanisms and introduce the pathological mechanism of glutamate excitotoxicity in Alzheimer's disease(AD), Parkinson's disease(PD), depression and epilepsy.Finally, this review briefly describes the regulatory effects of broad-spectrum glutamic satellite modulators, marine compounds and Chinese herbal medicines on the glutamatergic system.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-923443

ABSTRACT

@#Objective    To investigate the independent risk factors associated with postoperative acute respiratory distress syndrome in patients undergoing type A aortic dissection surgery. Methods    The clinical data of 147 patients who underwent acute type A aortic dissection surgery in the First Affiliated Hospital of Anhui Medical University from 2015 to 2019 were retrospectively analyzed. There were 110 males at age of 51.9±10.1 years and 37 females at age of 54.3±11.1 years. According to whether the patients developed ARDS after surgery, all of the patients were divided into a ARDS group or a non-ARDS group. Logistic regress analysis was utilized to establish the predictive mode to identify the independent risk factors related to ARDS. Results    Of the patients, 25 developed postoperative ARDS. Among them, 5 patients were mild ARDS, 13 patients were moderate, and 7 patients were severe ARDS. Multivariate logistic regression analysis showed that deep hypothermic circulatory arrest time [odds ratio (OR)=1.067, 95% confidence interval (CI) 1.014-1.124, P=0.013], cardiopulmonary bypass time (OR=1.012, 95%CI 1.001-1.022, P=0.027) and perioperative plasma input (OR=1.001, 95%CI 1.000-1.002, P=0.011) were independently associated with ARDS in patients undergoing acute A aortic dissection surgery. Receiver operating characteristic (ROC) curve analysis demonstrated a good discrimination ability of the logistic regression model, with an area under the curve of 0.835 (95%CI 0.740-0.929, P=0.000). Conclusion    Duration of deep hypothermic circulatory arrest, cardiopulmonary bypass time and perioperative plasma are independent risk factors for postoperative ARDS in patients undergoing type A aortic dissection surgery.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-934386

ABSTRACT

The pre-S/S gene of hepatitis B virus (HBV) can encode for the production of large, medium and small surface protein. Different protein expression levels and their composition ratios have certain influences on the diagnosis, treatment and outcome of HBV infection. It is of great significance to clarify the functions of large, medium and small surface protein as serum markers and to explore their value in the diagnosis and treatment of HBV infection. In this paper, the expression status, detection methods and clinical significance of the three HBV proteins were reviewed.

12.
Preprint in English | medRxiv | ID: ppmedrxiv-21263853

ABSTRACT

Pediatric COVID-19 (pCOVID-19) is rarely severe, however a minority of SARS-CoV-2-infected children may develop MIS-C, a multisystem inflammatory syndrome with significant morbidity. In this longitudinal multi-institutional study, we used multi-omics to identify novel time- and treatment-related immunopathological signatures in children with COVID-19 (n=105) and MIS-C (n=76). pCOVID-19 was characterized by enhanced type I IFN responses, and MIS-C by type II IFN- and NF-{kappa}B dependent responses, matrisome activation, and increased levels of Spike protein. Reduced levels of IL-33 in pCOVID-19, and of CCL22 in MIS-C suggested suppression of Th2 responses. Expansion of TRBV11-2 T-cell clonotypes in MIS-C was associated with inflammation and signatures of T-cell activation, and was reversed by glucocorticoids. The association of MIS-C with the combination of HLA A*02, B*35, C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load. Use of IVIG was identified as a confounding factor in the interpretation of autoantibody levels.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-912611

ABSTRACT

Objective:Based on the analysis of case report and case series studies involving COVID-19 pregnant women in China, we aimed to discuss the updated management requirements for publication of scientific papers at hospitals in the new circumstances and context.Methods:The case report and case series studies published by domestic scholars in the early stage of COVID-19 outbreak were retrieved. Bibliometrics were used to analyze the research time, research content and research objects of the included literatures.Results:Nearly 200 cases (55%) of the 360 cases of COVID-19 pregnant women could not be clearly excluded from the possibility of repeated reporting. However, all these cases were not disclosed in the paper for possible repeated report.Conclusions:Potential repeated report problem may cause trouble for later meta-analysis, which also may have negative impact for the development of clinical guidelines. The departments of scientific research management at hospital should pay more attention to the management of patient′s data in scientific papers, so that it can better serve the accurate assessment of disease characteristics and epidemic situation, as well as the scientific formulation of clinical guidelines and control strategies.

14.
Chinese Pharmacological Bulletin ; (12): 724-730, 2021.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014425

ABSTRACT

Aim To explore compound Chaijin Jieyu tablets on expression of GABA receptor in brain regions of depressive insomnia rats. Methods Seventy-two male SD rats were randomly divided into control, model, positive drug (venlafaxine hydrochloridel3. 5 mg · kg

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-885920

ABSTRACT

Objective:To examine the infection of the enterovirus and human herpes virus in children with suspected encephalitis.Methods:A total number of 365 suspected encephalitis cases were included in this study from August 2017 to December 2019 in Hunan Children′s Hospital. The clinical samples, the cerebrospinal fluid (CSF), serum, sputum, stool and urine were collected and preserved at-80 ℃condition. The enterovirus (EV) and human herpesvirus (HHV) were examined by a one-step nested reverse transcription PCR(RT-PCR) and a real-time fluorescent quantitative PCR (qPCR), respectively. The positive rate of the two viruses in clinical specimens of children with suspected encephalitis was examined. Among all cases, 132 cases were diagnosed with EV encephalitis or HHV encephalitis.Results:the EV encephalitis were identified in 20.5% (75/365) children with suspected viral encephalitis; whereas HHV encephalitis infection was identified as 15.6% (57/365). Among the 75 cases of EV encephalitis, echo 6 was the main sub-type of these diseases 52.0% (39/75) and others were EV71 (30.7%, 23/75), echo11 (6.7%, 5/75), Coxsackie virus A group 6(CA6, 4.0%, 3/75), echo30 (1.3%, 1/75), echo9 (1.3%, 1/75), echo4 (1.3%, 1/75),Coxsackie virus B group 1(CB1, 1.3%, 1/75))and poliovirus(1.3%, 1/75).Human herpes virus type 6 (HHV6) was the most common pathogen in 57 cases of HHV encephalitis, accounting for 35.1% (20/57).The other pathogens were Cytomegalovirus (CMV, 31.6%, 18/57), Epstein-Barr virus (8.8%, 7/57), Herpes simplex virus 1 (HSV1, 10.5%, 6/57), HSV2 (8.8%, 5/57), and Varicella zoster virus (VZV, 1.8%, 1/57) .The virus in CSF detected significantly earlier than that in serum after onset. Virus could be detected in CSF 2-7 days after onset,but 7-26 days in serum. Conclusions:This study uses nested PCR and qPCR to detect pathogens in clinical specimens of children. This not only expands our understanding of the clinical examination and diagnosis of viral encephalitis in children, but also promotes the method of this study to benefit more children.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-881214

ABSTRACT

@#Objective    To compare the short-term outcomes of surgical repair for atrial septal defect (ASD) with a robotic (da Vinci Si) approach versus a conventional open procedure. Methods    Clinical data of 140 patients undergoing ASD closure in the First Affiliated Hospital of Anhui Medical University from January 2016 to May 2020 were retrospectively analyzed. The patients were divided into a robotic group and a sternotomy group according to different surgical methods. In the robotic group, there were 67 patients including 20 males and 47 females at a median age of 40.0 (25.0) years, and in the sternotomy group there were 73 patients including 23 males and 50 females at a median age of 41.0 (29.0) years. Multivariate linear regressions were used to produce risk-adjusted analysis of pertinent clinical characteristics. Kaplan-Meier analysis was performed to compare the speed of sternotomy versus robotic group returning to exercise or daily life. Results    Robotic-assisted surgery was associated with significantly shorter 24 h postoperative drainage volume [220.0 (210.0) mL vs. 345.0 (265.0) mL, P<0.001], mechanical ventilation [6.0 (11.0) h vs. 8.0 (11.0) h, P=0.024], intensive care unit length of stay (LOS) [19.0 (19.0) h vs. 22.0 (25.0) h, P=0.005], postoperative hospital LOS [9.0 (5.0) d vs. 10.0(6.0) d, P=0.003], and a lower rate of perioperative blood transfusion (28.36% vs. 84.93%, P<0.001). After controlling for patient comorbidity in the multiple regression model, there remained a trend toward decreased 24 h postoperative drainage volume (β=–115.30, 95%CI–170.78 to –59.82, P<0.001), mechanical ventilation (β=–4.96, 95%CI –8.33 to –1.59, P=0.004) and postoperative hospital LOS (β=–2.31, 95%CI –3.98 to –0.63, P=0.007) in the robotic group. Kaplan-Meier analysis revealed that patients returned to exercise or daily life earlier in the robotic group [35.0 (32.0) d vs. 90.0 (75.0) d, P<0.001]. Conclusion    Closure of ASD can be performed safely and effectively via robotic approach. And the minimally invasive technique is beneficial to postoperative recovery.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-871993

ABSTRACT

At present, the situation of prevention and treatment of hepatitis B(HBV) infection in China is still serious. Factors affecting the course and outcome of HBV infection mainly include virus and hosts. While exploring the new clinical significance of HBV infection classic diagnostic indicators such as hepatitis B sunface antigen, hepatitis B core antibody and HBV DNA, more attention should be paid to the application value and prospect of new indicators such as HBV RNA and hepatitis B core-related antigen. With the proposing of the omics concept and the development of technology, people begin to focus on HBV infection with the concept of omics and integrate genomics, metabolomics, proteomics, etc., to achieve the goal of accurate diagnosis.

19.
Article in English | WPRIM (Western Pacific) | ID: wpr-773387

ABSTRACT

OBJECTIVE@#This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosis antigen Rv0674.@*METHODS@#To evaluate the diagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA.@*RESULTS@#The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/Poly I:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high- and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotype characterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines.@*CONCLUSION@#Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.


Subject(s)
Adult , Aged , Animals , Female , Humans , Male , Mice , Middle Aged , Young Adult , Antigens, Bacterial , Allergy and Immunology , Immunity, Cellular , Immunity, Humoral , Mice, Inbred BALB C , Tuberculosis , Diagnosis , Allergy and Immunology
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-712119

ABSTRACT

Objective The study aims to investigate the associationbetweencholesterol 7α-hydroxylase (CYP7A1) gene polymorphism and different clinical outcomes after Hepatitis B virus (HBV)infection in Fujian Han population and lay a foundation for understanding the mechanisms of genesis anddevelopment of HBV-related diseases.Methods Case-control study was conducted.586 patients of HBVpersistent infection without antiviral therapy and 225 HBV rehabilitation patients (35-55 years old) werecollected from May 2015 to June 2016 in the Liverish Center of First Clinical College of Fujian MedicalUniversity.The group of HBV persistent infection without antiviral therapy included 246 patients with chronichepatitis B, 177 patients with hepatitis B-related cirrhosis, and 163 patients with hepatitis B-related liver cancer.The rs3824260, rs4738687and rs8192871 loci of CYP7A1 gene were detected by improved multipleligase detection reaction (iMLDR).Logistic regression analysis and chi-square test were used to analyze thegenotyping results.Results Three SNPs ( single nucleotide polymorphisms ) of CYP7A1 gene wereselected and compared between HBV persistent infection group and HBV rehabilitation group and betweenchronic hepatitis B subgroup, liver cirrhosis subgroup and liver cancer subgroup.After adjustment for factorsincluding age andgender, there was no significant difference in the distribution of rs3824260 genotype amongthe groups(χ2 =1.565,P =0.459), however,the frequency of allele C in HBV rehabilitation group wassignificantly higher than in HBV persistent in fectiongroup for men (χ2 =4.365,P =0.037), whereas thefrequency of rs3824260 CC and CT was more likely to be observed in liver cancer group than in non -livercancer group (chronic hepatitis B subgroup and liver cirrhosis subgroup ) for women (χ2 =5.768,P =0.012;χ2 =10.130,P =0.001).The frequency of rs4738687 GG genotype was more likely to be observed innon-liver cancer group than in liver cancer group (χ2 =4.403,P =0.041;χ2 =6.940,P =0.009).Theresults of gender stratification showed that there were significant differences in the distribution of rs 4738687among the HBV persistent infection groups for men (χ2 =10.697,P =0.030), however, there was nosignificant difference in the distribution of rs4738687 among the HBV persistent infection groups for women(χ2 =4.627,P =0.329), and there was no significant difference in the distribution of genotype frequencyand allele frequency among all groups(χ2 =0.489,P =0.792).There was no significant difference after sexstratification either (χ2 =1.282, P =0.526;χ2 =1.565,P =0.465) .Conclusions These findingssuggested that CYP7A1 gene polymorphism was related todifferent clinical outcomes in Fujian Hanpopulation.The rs3824260 mutation had a certain gender preference and the mutation allele was detected ina higher proportion in male patients.Male HBV patients with rs3824260 C allele had more chance ofswitching to rehabilitation.The rs4738687 was likely to be related to the occurrence of liver cancer in FujianHan population, and GG genotype may delay the occurrence and development of liver cancer especially in themale group.The rs8192871 was not found to be related to the different clinical outcomes of HBV infection.

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