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Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis ( Mtb) that seriously endangers human health. Mtb induces epigenetic changes in the host to regulate host genome transcription and immune response, which plays an important role in the growth and replication of Mtb and the development and outcome of TB. Since epigenetic regulation occurs early and is reversible, it has been extensively studied in the pathogenesis of various diseases and has great potential as a molecular target. This paper reviewed the epigenetic changes in host after Mtb infection, including DNA methylation and miRNA, and summarized the role of epigenetics in the pathogenesis of TB and the research progress in potential diagnostic markers.
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Tuberculosis as an infectious disease is still one of the leading causes of morbidity and mortality throughout the world. The current diagnosis and treatment strategies cannot solve all clinical problems. Newer and more rapid tuberculosis diagnostic technologies with higher sensitivity, as well as more personalized host-oriented treatment strategies are still the important research directions in the future. Tuberculosis-related long non-coding RNAs (lncRNAs) have been one of the research hot spots in recent years. A series of lncRNA candidates with the potential diagnostic value for tuberculosis have been obtained using transcriptome sequencing and microarray technology. Meanwhile, lncRNAs have been also discovered to play an important role in antimicrobial defense mechanisms by regulating immune cell differentiation, autophagy/apoptosis, inflammatory responses and other biological processes. The current findings of lncRNAs as diagnostic candidates and their roles in tuberculosis were summarized in this review.
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The definition of adjuvant in immunology is the non-specific immunopotentiator, which only performs auxiliary functions. With the appearance of various adjuvants and their successful application in some vaccines against infectious disease, they have received extensive attention and been studied in-depth. This review focused on the types, functions and prospects of adjuvants used in tuberculosis vaccines, aiming to provide reference for adjuvant selection and development in future.
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Objective:To investigate the correlation between serum procalcitonin (PCT) level and intracranial atherosclerotic burden (ICASB) in patients with ischemic stroke.Methods:From January 2019 to December 2020, consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Jiangsu Provincial Second Chinese Medicine Hospital were enrolled. Chemiluminescence immunoassay was used to detect serum PCT levels, and ICASB was evaluated based on the results of cranial magnetic resonance angiography. Univariate analysis was used to determine the baseline data among the different ICASB score groups. Then the independent correlation between serum PCT level and ICASB was determined by the ordinal logistic regression analysis. At the same time, the correlation between serum PCT level and ICASB was determined by the linear regression analysis. Results:A total of 291 patients with acute ischemic stroke were enrolled, including 161 male (55.3%), aged 64.5±8.4 years; median serum PCT level was 0.053 μg/L. According to the ICASB score, the patients were divided into 0 group ( n=155, 53.3%), 1-3 group ( n=95, 32.6%) and >3 group ( n=41, 14.1%). Univariate analysis showed that the age, serum homocysteine and PCT level, as well as the proportion of diabetes were significantly higher in the higher ICASB score group, while the proportion of the patients with atrial fibrillation was significantly lower (all P<0.05). Ordinal multivariable logistic regression analysis showed that higher serum PCT level was an independent factor for higher ICASB score (the 4 th quartile vs. the 1 st quartile: odds ratio, 2.015, 95% confidence interval 1.052-3.927; P=0.043). Multiple linear regression analysis showed that the serum PCT level was positively correlated with the ICASB score ( r=0.253, P=0.001). Conclusion:The serum PCT level is correlated with ICASB.
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Objective To investigate the correlation between serum adiponectin levels and post-stroke cognitive impairment (PSCI). Methods From January 2018 to December 2018, consecutive patients with ischemic stroke admitted to the Departments of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, Dongguan Changping Hospital, and Jiangsu Provincial Second Chinese Medicine Hospital were enrolled. Serum adiponectin concentration was detected by radioimmunoassay. The cognitive function assessment was performed 1 month after the onset of stroke using the Montreal Cognitive Assessment (MoCA). The total score of MoCA <22 was defined as PSCI. Univariate analysis was used to compare the baseline data between groups, and multivariate logistic regression analysis was used to determine the association between serum adiponectin levels and PSCI. Results A total of 257 patients with acute ischemic stroke were enrolled, with age 66.5 ± 9.9 years, 139 (54.1% ) males, and 91 (35.4% ) with PSCI. Age (68.2 ± 8.1 years vs. 65.6 ± 10.8 years; t=2.007, P=0.046 ), homocysteine (16.0 ± 6.2 μmol/L vs. 14.5 ± 4.5 μmol/L; t= 2.208, P= 0.028 ), and high-sensitivity C-reactive protein ( 7.0 [3.3-9.9] mg/L vs. 4.7 [2.2-9.6] mg/L; Z=2.346, P=0.019 ) as well as the proportion of hypertension (64.8% vs. 50.6% ; χ2 =4.824, P=0.028), diabetes (33.0% vs. 21.1% ; χ2 =4.392, P=0.036), leuko-araiosis (47.2% vs. 32.5% ; χ2 =5.422, P=0.020) and diffusion weighting imaging-Alberta Stroke Project early CT score 0-7 (59.3% vs. 41.4% ; χ2 =6.942, P=0.008) in the PSCI group was significantly higher than that of the non-PSCI group, while the adiponectin level was significantly lower than that of the non-PS-CI group (5.4 [3.5-8.4] mg/L vs. 7.0 [5.3-9.3] mg/L; Z=3.624, P=0.001 ). Multivariate logistic regression analysis showed that after adjusting for the confounding factors, the lower serum adiponectin level was an independent risk factors for PSCI (the 1st quartile group vs. the 4th quartile group: odds ratio 2.152, 95% confidence interval 1.119-5.039; P=0.047). Conclusions Low serum adiponectin level might be an independent risk factor for PSCI in patients with ischemic stroke.
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Objective To discuss the effects of acupuncture therapy on resting state functional magnetic resonance imaging (fMRI) in patients with ischemic stroke; To explore the central mechanism of acupuncture therapy.Methods Ten is chemic stroke patients with hemiplegia limbs and ten matched control subjects were included. Treatment group was given anti-platelet aggregation, anticoagulation, and nutrition brain cell therapy. At the same time, acupuncture therapy was given, taking Jianyu, Quchi, Shousanli, Waiguan, Hegu, Zusanli, Fenglong, Yanglingquan, Sanyinjiao, and Taichong, with even reinforcing-reducing method, and retaining the needle 30 min, manipulating needle every 10 min, once a day, 5 times a week, needle stopping for 2 d, for continuous 30 d. The health group did not undergo any treatment. BOLD-fMRI imaging technique was used, and based on RSET1.8 software, the parameters of brain activity before and after treatment were observed by amplitude of low frequency fluctuation (ALFF) method. The Results were compared with healthy group. Results Before treatment, the ALFF value of left caudate nucleus, putamen and globus pallidus in the treatment group was lower than that in the health group, and the ALFF value of bilateral precentral and postcentral gyrus, left grus frontalis superior, gyrus frontalis medius, gyrus temporalis medius and precuneus was higher than the health group (P<0.05). After treatment, the ALFF value in left caudate nucleus, putamen and globus pallidus in the treatment group was higher than that before treatment, and the ALFF value in left gyrus frontalis superior, gyrus frontalis medius and precuneus decreased than before group (P<0.05).Conclusion In the resting state of the ischemic stroke patients with hemiplegia limbs, the principal injured brain regions are caudate nucleus, putamen and globus pallidus. Acupuncture has a regulatory role for these brain areas, presumably may be the central mechanism of efficacy.
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Members of the tripartite-motif (TRIM) protein family share a highly conserved domain architecture known as RBCC motif,which is composed of a RING finger domain,one or two B-box domains,a coiled-coil domain as well as diverse types of C-terminal regions.TRIM proteins can not only maintain the normal physiological functions of the body,but also regulate the development of various diseases.In the current review,we focus on recent advances in the structures of TRIM proteins and their functions in the development of viral infection,cancer and neurodegenerative disease.
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Objective The abnormal ankle-brachial index ( ABI) is associated with the incidence of cardiocerebral vascular diseases, but little is known about its relationship with cerebral microbleeds (CMB).This study aimed to investigate the correlation be-tween ABI≤0.9 and different distribution patterns of CMB . Methods We enrolled 187 patients with acute lacunar infarction , inclu-ding 115 non-CMB cases and 72 CMB cases (20 strictly lobar, 24 strictly deep, and 28 lobar and deep).We analyzed the differences between the two groups and the association of abnormal ABI with the occurrence and distribution of CMB by logistic regression analysis . Results ABI≤0.9 was found in 57 (30.5%) of the patients, with a significantly higher incidence rate in the CMB group than in the non-CMB group (43.1%vs 22.6%, P=0.003).The level of ABI was negatively correlated with the number of CMBs (r=-0.211, P=0.006).Multivariate logistic regression analysis after adjusted for confounders indicated that ABI ≤0.9 was significantly associated with the presence of CMB (OR=2.363;95%CI:1.181-4.729), deep CMB (OR=3.434;95%CI:1.283-9.187), and lobar and deep CMB ( OR=2.837;95%CI:1.098-7.333) in patients with ischemic cerebrovascular disease . Conclusion Decreased ABI is a risk factor of CMB, particularly deep CMB, in patients with ischemic stroke.
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Objective To study the effects of prokaryotic ubiquitin-like protein ( Pup)-proteasome system on the growth of Mycobacterium strains.Methods The genes encoding Pup ( pup gene) and protea-someβsubunit ( prcB gene) were respectively knocked out from Mycobacterium smegmatis ( M.sm) strains by homologous recombination.The growth and viability of the wild-type and mutant strains of M.sm were an-alyzed under normal culture condition and under hypoxia as well as anaerobic conditions.Results The pup and prcB genes were completely and precisely knocked out from M.sm strains and the mutant strains were named △SM-Pup and△SM-prcB, respectively.The△SM-Pup strains grew faster than the wild type ( WT) and△SM-prcB strains.No significantly differences in the growth of M.sm were found between the WT and△SM-prcB strains.Conclusion The Pup-proteasome system was involved in the growth of M.sm, espe-cially the pup gene.There was difference between pup and prcB genes in regulating the growth of M.sm.The functions and influences of Pup-proteasome system still need further investigation.
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<p><b>BACKGROUND</b>Genetic variations in the interferon-gamma (IFN-γ) receptor 1 gene (IFNGR1) may contribute to tuberculosis (TB) risk in different populations. Many studies have investigated the relationship between IFNGR1 56C/T polymorphism and the susceptibility to TB, but have yielded conflicting results. A comprehensive meta-analysis is needed to provide a more accurate estimation of the relationship between them.</p><p><b>METHODS</b>A literature search based on a combination of manual and computer-based methods was conducted on four English databases (PubMed, Science Direct, SpringerLink, and EBSCO) and three Chinese databases (Wanfang, CQVIP, and Chinese National Knowledge Infrastructure databases). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using either the fixed-effects model or the random-effects model for different genetic models based on the heterogeneity examination.</p><p><b>RESULTS</b>A total of six studies comprising 1 497 confirmed TB cases and 1 802 controls were included in this meta-analysis. Overall, no significant association was observed between IFNGR1 -56C/T polymorphism and TB susceptibility (C vs. T, OR = 0.90, 95% CI 0.69-1.17; CC vs. TT, OR = 0.87, 95% CI 0.65-1.18; TC vs. TT, OR = 1.031, 95% CI 0.872-1.219; CC+TC vs. TT, OR = 0.89, 95% CI 0.64-1.26; CC vs. TC+TT, OR = 0.92, 95% CI 0.66-1.29). In subgroup analysis, a significant association was found in the dominant model (CC+TC vs. TT, OR = 1.24, 95% CI 1.02-1.51) in Africans, but not in Asians or Caucasians.</p><p><b>CONCLUSIONS</b>Our meta-analysis did not provide enough powerful evidence to identify a significant association between IFNGR1 -56C/T polymorphism and TB susceptibility in the overall population. In subgroup analysis, it indicates that IFNGR1 -56C/T is possibly associated with increased TB risk in Africans, but not in Asians or Caucasians. However, larger sample size and better-designed case-control studies are needed to validate these findings.</p>
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Humans , Genetic Predisposition to Disease , Genetics , Polymorphism, Single Nucleotide , Genetics , Receptors, Interferon , Genetics , Tuberculosis , GeneticsABSTRACT
Objective To analyze the characteristics and significance of matrix metalloproteinase-9 (MMP-9) expression in the pathophysiological processes of tuberculous meningitis in mice.Methods Sixteen mice were intracerebroventricularly injected with H37RV suspension as the model group.Meanwhile,the other 16 mice were injected with 0.9％ sodium chloride solution as the control group.Thirty days later,all mice were decapitated and the brain tissue were respectively used to for Mycobacterium tuberculosis (M.tuberculosis) incubation,pathological changes observation,MMP-9 activity detection by zymography,blood-brain-barrier permeability and moisture content detection,and immunofluorescence stain of MMP-9,glial fibrillary acidic protein (GFAP) and integrin αM (OX-42).The t test was used to compare the differences between the two groups.Results Every experimental mouse was injected with (1.271±0.111) × 106 colony-forming units (cfu) M.tuberculosis.Thirty days later,the amount of M.tuberculosis in brain tissue homogenates was (4.900± 1.407) × 104 cfu/mL,and the hematoxylin and eosin staining showed dilatation of subarachnoid and ventricular and infiltration of a large number of inflammatory cells.The cumulative absorbance (A) of MMP-9 bands of brain tissue was 47 821 ± 19 932 in the model group and 10 082 ± 3 544 in the control group.The difference was statistically significant (t =3.728,P=0.010).The evans blue (EB) content of brain tissue was (11.8 ± 3.6) μg/g in model group and (4.7 ±3.4) μg/g in control group.The difference was statistically significant (t=2.887,P=0.028).The moisture of brain tissue was 0.849±0.035 in model group and 0.775±0.037 in control group.The difference was statistically significant (t=2.925,P=0.026).The immunofluorescence staining showed that the infected brain tissue expressed high degrees of MMP-9,GFAP and OX-42.And MMP-9 was overlapped with both GFAP and OX-42 obviously.Conclusions The activity of MMP-9 is significantly enhanced in brain tissue of mice suffering from tuberculous meningitis and participates in blood-brain barrier damage,tissue edema and inflammatory cells exudation.Microglia cells-astrocytes network is involved in the secretion of MMP-9.
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Objective To detect specific polymorphisms in Toll-interleukin 1 receptor domain containing adaptor protein(TIRAP) coding region for Chinese Han population, and verify whether they are associated with susceptibility to tuberculosis. Methods Search TIRAP polymorphisms by sequencing in small sample; detect single nucleotide polymorphism(SNP) by ligase detection reaction technique in large sample; analyze whether polymorphisms are related to tuberculosis by statistic methods. Results Four polymorphisms were present in the TIRAP coding region. 394A had higher frequencies in the tuberculosis(TB)group than the control. But allelic and genotypic analysis showed that there were no significant difference in statistic between TB patients and controls(P>0.05). The SNP G164A mutation related with TB patient's condition. Comparing to controls, retreatment patients' allelic frequencies had significant difference in statistic(P<0.05), sputum positive patients and lung cavitation patients had lower 164A frequencies. Conclusion TIRAP coding region polymorphisms may be risk factors for TB occurrence and development in Chinese Han population.
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Objective To investigate the risk factors for reduced renal function in patients with ischemic stroke.Methods The medical records of patients with ischemic stroke were analyzed retrospectively.They were divided into normal renal function group and reduced renalfunction group.Reduced renal function was defined as estimated glomerular filtration rate (eGFR) ＜60 ml/(min·1.73 m2).Multivariate logistic regression analysis was used to identify the risk factors for reduced renal function in patients with ischemic stroke.Results A total of 805 patients with ischemic stroke were enrolled in the study.8.8％ of patients had a reduced renal function.There was no significant differences in the proportion of patients with mild and moderate neurological deficit between the reduced renal function group and the normal renal function group (all P ＞ 0.05),however,the proportion of patients with severe neurological deficit was significantly higher than that in the normal renal function group (8.4％vs.2.6％,x2 =5.573,P =0.017).The proportion of small artery occlusion in the reduced renal function group was sigaificantly higher than that in the normal renal function group (66.2％ vs.46.5％,x2 =9.962,P =0.002),and the proportion of large artery atherosclerosis was significantly lower than that in the normal renal function group (19.7％ vs.43.5％,x2 =15.045,P =0.000).Multivariate logistic regression analysis indicated that old age (odds ratio [ OR] 3.301,95％ confidence interval [ CI],1.575 to 6.918; P=0.002) was the most important independent risk factor for reduced renal function,then was female (OR,2.291,95％ CI 1.355to 3.872; P=0.002) and hyperlipidemia (OR,2.527,95％ CI 1.095 to 5.831; P=0.030).Conclusions Reduced renal function in patients with ischemic stroke is strongly associated with old age,female,and hyperlipidemia.
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Objective To investigate the immune protection of heparin-hinding hemagglutinin ad-hesin(HBHA) and to estimate its potential diagnostic value. Methods Native HBHA were used to stimu-late peripheral blood mononuelear cells (PBMCs) from different infected-cases including PPD negative healthy control, PPD positive latent tuberculosis(LTB) infection, pulmonary tuberculosis, and the IFN-γ/in the supernatant of culture was detected. Meanwhile, HBHA specific IgG antibody in the sera was detected by ELISA. Results The middle level of HBHA specific IFN-γ of the three groups were 49.5 pg/ml, 781.9 pg/ml and 341.8 pg/ml, respectively. IFN-γ of latent tuberculosis group was much higher than that of the control, and slightly higher than that of the patients with pulmonary tuberculosis. And the absorbency of the IgG antibody to HBHA in the three groups was 0.212±0.066, 0.224 ± 0.076 and 0.285±0.078. lgG an-tibody in the patients with pulmonary tuberculosis is higher than that of the healthy, including the control and the latent tuberculosis infection. Conclusion HBHA has good immunogenieity, and it can stimulate the LTB to release high level IFN-γ, suggests that the LTB doesn't develop active tuberculosis may rely on its protection. HBHA specific. IFN-γ release may identify 1,333 from the healthy. Anti-HBHA antibody plays an auxiliary role in the diagnosis of pulmonary tuberculosis.
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Objective To assess the application of IS6110-restriction fragment length polymorphism (RFLP)and Spoligotyping in the epidemiology of tuberculosis and to discuss the characteristic of the Mycobacterium tuberculosis in different regions in China.Methods 158 isolates of Mycobacterium tuberculosis strains, were verified by IS6110-RFLP and spoligotyping.Results The discriminatory power of IS6110-RFLP was higher than that of spoligotyping. The result of spoligotyping was compared with the international spoligotype database. Fourteen types belonged to the shared types, in which the type 1 was epidemic and widely,called Beijing genotype. There was significantly difference among the mycobacterium tuberculosis between Guangdong and other regions in clustered rate and the proportion of Beijing genotype (P
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Objective To assess susceptibility of to 173 clinical M.tuberculosis isolates to by Micro-well Phage Replication Assay(MPRA).Methods To prepare the isolates and expose them to rifampin . To prepare phage D29 suspension . MPRA array for the susceptibility to rifampin.Results Compared with the absolute concentration method ,there were the same result of 38 isolate in 42 susceptible strains and of 124 isolate in 131 resistant strains. Between result of MPRA assay and absolute concentrstion (method,) concordance was 93.6%(38/42), susceptibility was 94.9%(124/131) and specificity is 90.5%((38/42).)Conclusion MPRA assay is a good and rapid method for drug susceptibility of rifampin.