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  • 1
    In: Communications Biology, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2023-02-07)
    Abstract: Global control of the tuberculosis epidemic is threatened by increasing prevalence of drug resistant M. tuberculosis isolates. Many genome-wide studies focus on SNP-associated drug resistance mechanisms, but drug resistance in 5–30% of M. tuberculosis isolates (varying with antibiotic) appears unrelated to reported SNPs, and alternative drug resistance mechanisms involving variation in gene/protein expression are not well-studied. Here, using an omics approach, we identify 388 genes with lineage-related differential expression and 68 candidate drug resistance-associated gene pairs/clusters in 11 M. tuberculosis isolates (variable lineage/drug resistance profiles). Structural, mutagenesis, biochemical and bioinformatic studies on Rv3094c from the Rv3093c-Rv3095 gene cluster, a gene cluster selected for further investigation as it contains a putative monooxygenase/repressor pair and is associated with ethionamide resistance, provide insights on its involvement in ethionamide sulfoxidation, the initial step in its activation. Analysis of the structure of Rv3094c and its complex with ethionamide and flavin mononucleotide, to the best of our knowledge the first structures of an enzyme involved in ethionamide activation, identify key residues in the flavin mononucleotide and ethionamide binding pockets of Rv3094c, and F221, a gate between flavin mononucleotide and ethionamide allowing their interaction to complete the sulfoxidation reaction. Our work broadens understanding of both lineage- and drug resistance-associated gene/protein expression perturbations and identifies another player in mycobacterial ethionamide metabolism.
    Type of Medium: Online Resource
    ISSN: 2399-3642
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2919698-X
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  • 2
    In: Endocrine, Springer Science and Business Media LLC, Vol. 72, No. 1 ( 2021-04), p. 157-170
    Type of Medium: Online Resource
    ISSN: 1355-008X , 1559-0100
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2074043-8
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  • 3
    In: Ecotoxicology and Environmental Safety, Elsevier BV, Vol. 210 ( 2021-03), p. 111872-
    Type of Medium: Online Resource
    ISSN: 0147-6513
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1466969-9
    SSG: 24,1
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Codon Publications ; 2023
    In:  Allergologia et Immunopathologia Vol. 51, No. 2 ( 2023-03-01), p. 27-35
    In: Allergologia et Immunopathologia, Codon Publications, Vol. 51, No. 2 ( 2023-03-01), p. 27-35
    Abstract: Background: Tracheobronchial stenosis due to tuberculosis (TSTB) seriously threatens the health of tuberculosis patients. The inflammation and autophagy of fibroblasts affect the development of TSTB. Triamcinolone acetonide (TA) can regulate the autophagy of fibroblasts. Nevertheless, the impact of TA on TSTB and underlying mechanism has remained unclear. Objective: To study the impact of TA on TSTB and underlying mechanism. Material and Methods: In order to simulate the TSTB-like model in vitro, WI-38 cells were exposed to Ag85B protein. In addition, the cell counting kit (CCK)-8 assay was applied to assess the function of TA in Ag85B-treated WI-38 cells. Quantitative real-time polymerase chain reaction was applied to detect the mRNA level of sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3a), and autophagy-related proteins were evaluated by Western blot analysis. Vascular endothelial growth factor (VEGF) level was investigated by immunohistochemical staining. Enzyme-linked immunosorbent serologic assay was applied to detect the secretion of inflammatory cytokines. Furthermore, hematoxylin and eosin staining was applied to observe tissue injuries. Results: Ag85B affected WI-38 cell viability in a limited manner, while TA notably suppressed Ag85B-treated WI-38 cell viability. TA induced the apoptosis of Ag85B-treated WI-38 cells in a dose-dependent manner. In addition, Ag85B-treated WI-38 cells demonstrated the u pregulation of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ), and fibrotic proteins (transforming growth factor-beta [TGF-β] and vascular endothelial growth factor [VEGF] ), which can be significantly destroyed by the TA. Meanwhile, TA reversed Ag85-induced inhibition of cell autophagy by mediation of p62, LC3, and Beclin1. Furthermore, silencing of SIRT1/FOXO3a pathway could reverse the effect of TA on the autophagy of Ag85B-treated cells. Conclusion: TA significantly induced the autophagy of fibroblasts in Ag85B-treated cells by mediation of SIRT1/FOXO3 pathway. This study established a new theoretical basis for exploring strategies against TSTB.
    Type of Medium: Online Resource
    ISSN: 0301-0546
    Language: Unknown
    Publisher: Codon Publications
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2011
    In:  Ophthalmic Epidemiology Vol. 18, No. 2 ( 2011-04), p. 54-60
    In: Ophthalmic Epidemiology, Informa UK Limited, Vol. 18, No. 2 ( 2011-04), p. 54-60
    Type of Medium: Online Resource
    ISSN: 0928-6586 , 1744-5086
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2011
    detail.hit.zdb_id: 1483138-7
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  • 6
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 57, No. 4 ( 2019-04)
    Abstract: Concerns about the specificity of the Xpert MTB/RIF (Xpert) assay have arisen, as false-positive errors in the determination of Mycobacterium tuberculosis complex (MTBC) infection and rifampin (RIF) resistance in clinical practice have been reported. Here, we investigated 33 cases where patients were determined to be RIF susceptible using the Bactec MGIT 960 (MGIT) culture system but RIF resistant using the Xpert assay. Isolates from two of these patients were found not to have any mutations in the rifampin resistance determining region (RRDR) region of rpoB and had good treatment outcomes with first-line antituberculosis (anti-TB) drugs. The remaining 31 patients included 5 new cases and 26 previously treated patients. A large number of well-documented disputed mutations, including Leu511Pro, Asp516Tyr, His526Asn, His526Leu, His526Cys, and Leu533Pro, were detected, and mutations, including a 508 to 509 deletion and His526Gly, were described here as disputed mutations for the first time. Twenty-one (81%) of the 26 previously treated patients had poor treatment outcomes, and isolates from 19 (90%) of these 21 patients were resistant to isoniazid (INH) as determined using the MGIT culture system. Twenty-seven of the 31 isolates with disputed rpoB mutations were phenotypically resistant to INH, 21 (78%) being predicted by GenoType MTBDR plus to have a high level of INH resistance. Most (77.4%) of the isolates with disputed mutations were of the Beijing lineage. These findings have implications for the interpretation of false-positive and disputed rifampin resistance Xpert MTB/RIF results in clinical samples and provide guidance on how clinicians should manage patients carrying isolates with disputed rpoB mutations.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    EManuscript Technologies ; 2015
    In:  International Journal of Medicine and Public Health Vol. 5, No. 4 ( 2015), p. 332-
    In: International Journal of Medicine and Public Health, EManuscript Technologies, Vol. 5, No. 4 ( 2015), p. 332-
    Type of Medium: Online Resource
    ISSN: 2230-8598
    Language: English
    Publisher: EManuscript Technologies
    Publication Date: 2015
    detail.hit.zdb_id: 2649717-7
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-3-8)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-3-8)
    Abstract: Background: Female Genital Tract (FGT) is an important micro-ecological area of human body. Microbiota in the lower reproductive tract may subsequently invade the uterine cavity during embryo implantation and produce immune responses. CBA/J×DBA/2 mating combination has been widely used as an abortion-prone mice model but whether microbiota existed in their uterine cavity remains unclear. In this context, the role of the microbial communities in immune response deserves attention. Objective: To investigate the relationship between the distribution of microbiota in the uterine cavity of CBA/J×DBA/2 abortion-prone mouse model and the immune imbalance of the maternal-fetal interface. Methods: In this study, female CBA/J mice were paired with male DBA/2 mice to develop an abortion-prone model (BA group), and with male BALB/c mice to build a standard pregnancy model (BC group). The non-pregnant female mice were served as the control group (C group). Uterine flushing fluid and sera were collected on day 13.5 of pregnancy. 16S rRNA sequencing technology was used to analyze the distribution of intrauterine microbiota. Phylogenetic Investigation of Communities were conducted to predict the microbiota functions by Reconstruction of Unobserved States (PICRUST) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The serum IL 10, INF-γ, and TNF-α levels were examined using Enzyme-linked immunosorbent assay (ELISA) method. Results: All samples were detected with microbial communities. The α diversity ( p = 0.00077) had significant differences among three groups. Proteobacteria was the most dominant phylum in C group (mean = 83.21%) and BA group (mean = 43.23%). Firmicutes was dominant in BC group (mean = 46.4%), as well as the second dominant one in C group (mean = 12.63%) and BA group (mean = 40.55%). Microbiota functions were associated with metabolism and immune response through the NOD-like receptor signaling pathway. The serum IL 10 level in BA group were significantly lower than that in BC group (10.14 ± 1.90 pg/ml, n = 8; vs. 19.03 ± 1.82 pg/ml, n = 10; p = 0.004). The serum TNF-α and INF-γ level in BA group were also significantly higher than that in BC group (523.1 ± 58.14 pg/ml, n = 8 vs. 310.3 ± 28.51 pg/ml, n = 10, p = 0.0029; 69.22 ± 5.38 pg/ml, n = 8 vs. 50.85 ± 2.45 pg/ml, n = 10, p = 0.0042). Conclusion: Microbial communities were colonized in uterine cavity of CBA/J mice both at non-pregnant stage and pregnant stage when mated with both BALB/c and DBA/2 male mice. The differentially abundant microbiome may be attributed to the immune tolerance through binding to the NOD-like receptor.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: European Journal of Medical Research, Springer Science and Business Media LLC, Vol. 28, No. 1 ( 2023-02-02)
    Abstract: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined. Methods The Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan–Meier curves, and subgroup analyses were conducted. Results The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P  = 0.007), and all-cause death (0.36% vs. 0.99%, P  = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P  = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16–0.78; ( P  = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14–0.94; ( P  = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups. Conclusions In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted. Clinical trial registration : https://www.clinicaltrials.gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014)
    Type of Medium: Online Resource
    ISSN: 2047-783X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2129989-4
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  • 10
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2014-12)
    Abstract: In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. Methods A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Results Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases’ spouses, sisters/brothers and those who were in contact with female Index Cases. Conclusions The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
    detail.hit.zdb_id: 2041550-3
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