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Pathogenesis AND Tuberculosis

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https://www.readbyqxmd.com/read/28215633/tlr-4-mirna-32-5p-fstl1-signaling-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages
#1
Zhi-Min Zhang, Ai-Rong Zhang, Min Xu, Jun Lou, Wei-Qiang Qiu
Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28210262/morphoproteomic-guided-host-directed-therapy-for-tuberculosis
#2
Robert E Brown, Robert L Hunter, Shen-An Hwang
In an effort to develop more effective therapy for tuberculosis (TB), research efforts are looking toward host-directed therapy, reprograming the body's natural defenses to better control the infection. While significant progress is being made, the efforts are limited by lack of understanding of the pathology and pathogenesis of adult type TB disease. We have recently published evidence that the developing lesions in human lungs are focal endogenous lipid pneumonia that constitutes a region of local susceptibility in a person with strong systemic immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#3
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 14, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28208905/n-acetylcysteine-combined-with-home-based-physical-activity-effect-on-health-related-quality-of-life-in-stable-copd-patients-a-randomised-controlled-trial
#4
Vijay Tukaram Salve, Jitesh S Atram
INTRODUCTION: Quality of life is adversely affected in Chronic Obstructive Pulmonary Disease (COPD), due to irreversible, progressive nature of the disease and limitations of current treatment options available. One of the important aim of treatment of COPD is to improve Quality of Life (QoL). Cigarette smoke contains numerous free radicals and other oxidants. Oxidative stress has been implicated in pathogenesis, progression of disease and exacerbation in COPD. Pulmonary tuberculosis, outdoor and indoor air pollution and many others are aetiologies of COPD in non-smokers...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28203440/tracheobronchial-tuberculosis-a-clinical-review
#5
REVIEW
Wen Ting Siow, Pyng Lee
Endobronchial tuberculosis (EBTB) is defined as tuberculous infection of the tracheobronchial tree. The exact pathogenesis is unclear, and it has a heterogenous clinical course. Its diagnosis requires the clinician to have a high index of suspicion based on clinical symptoms and radiological features. Computed tomography and bronchoscopy are useful tools in its evaluation. The goal of treatment is in the eradication of tuberculous bacilli with appropriate anti-tuberculous therapy. Use of corticosteroids is controversial for the prevention of tracheobronchial stenosis...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28203422/colobronchial-fistula-the-pathogenesis-clinical-presentations-diagnosis-and-treatment
#6
Jinbo Zhao, Nan Ma, Zhengwei Zhao, Jie Lei, Qiang Lu, Feng Tian, Yongan Zhou, Yong Han, Xiaofei Li
BACKGROUND: Colobronchial fistula (CBF) is rare and easy to be delayed in clinic. There is no systemic study about this disease. The pathogenesis, clinical presentations, diagnosis and treatment of CBF were analyzed in this study. METHODS: The clinical data from 37 cases of CBF, which included one case in our institute and the other 36 cases in literature from January 1960 to August 2016, were reviewed and analyzed. The etiology, clinical presentations, diagnostic and therapeutic methods, and outcomes were summarized...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28202315/mycobacterium-tuberculosis-chorismate-mutase-a-potential-target-for-tb
#7
REVIEW
Manjulatha Khanapur, Mallika Alvala, Maddela Prabhakar, K Shiva Kumar, R K Edwin, P S V K Sri Saranya, Raj Kumar Patel, Gopalakrishnan Bulusu, P Misra, Manojit Pal
Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway to form the essential amino acids, phenylalanine and tyrosine. Two genes encoding chorismate mutase have been identified in Mtb. The secretory form,∗MtbCM (encoded by Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Also, the inhibition of MtbCM may hinder the supply of nutrients to the organism. Indeed, the existence of chorismate mutase (CM) in bacteria, fungi and higher plants but not in human and low sequence homology among known CM makes it an interesting target for the discovery of anti-tubercular agents...
February 4, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28178325/prevalence-and-clinical-relevance-of-helminth-co-infections-among-tuberculosis-patients-in-urban-tanzania
#8
Francis Mhimbira, Jerry Hella, Khadija Said, Lujeko Kamwela, Mohamed Sasamalo, Thomas Maroa, Magreth Chiryamkubi, Grace Mhalu, Christian Schindler, Klaus Reither, Stefanie Knopp, Jürg Utzinger, Sébastien Gagneux, Lukas Fenner
BACKGROUND: Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania. METHODOLOGY: Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28159576/humoral-immune-profiling-of-mycobacterial-antigen-recognition-in-sarcoidosis-and-l%C3%A3-fgren-s-syndrome-using-high-content-peptide-microarrays
#9
REVIEW
Giovanni Ferrara, Davide Valentini, Martin Rao, Jan Wahlström, Johan Grunewald, Lars-Olof Larsson, Susanna Brighenti, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
INTRODUCTION: Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. METHODS: Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches...
January 31, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28149582/tracheobronchial-tuberculosis
#10
REVIEW
Vikas Pathak, Ray W Shepherd, Samira Shojaee
Tracheobronchial tuberculosis (TBTB) is reported in approximately 10% to 39% of the patients with pulmonary tuberculosis. It is defined as the tubercle infection of the trachea and or bronchi. Due to its non-specific presentation, insidious onset and normal chest radiography in about 10-20% of the patients, the diagnosis is delayed. Bronchoscopy is the most definite method of diagnosis which provides adequate specimens for microbiological and histopathological diagnosis. Tracheobronchial stenosis is one of the most common long term complications of TBTB resulting in significant morbidity...
December 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28141495/mycobacterial-phenolic-glycolipid-synthesis-is-regulated-by-camp-dependent-lysine-acylation-of-fadd22
#11
Sintu Samanta, Albel Singh, Priyanka Biswas, Apoorva Bhatt, Sandhya Visweswariah
The mycobacterial cell envelope is unique in its chemical composition, and has an important role to play in pathogenesis. Phthiocerol dimycocerosates (PDIMs) and glycosylated phenolphthiocerol dimycocerosates, also known as phenolic glycolipids (PGLs), contribute significantly to the virulence of M. tuberculosis. FadD22 is essential for PGL biosynthesis. We have recently shown in vitro that FadD22 is a substrate for lysine acylation by a unique cAMP-dependent, protein lysine acyl transferase found only in mycobacteria...
January 28, 2017: Microbiology
https://www.readbyqxmd.com/read/28135876/analysis-of-the-association-between-mycobacterium-tuberculosis-infection-and-immunoglobulin-a-nephropathy-by-early-secreted-antigenic-target-6-detection-in-renal-biopsies-a-prospective-study
#12
Sun Li, Teng Siyuan, Feng Jiangmin, Wang Hailong, Yao Li, Ma Jianfei, Wang Lining
OBJECTIVES: Immunoglobulin A nephropathy (IgAN) is the most frequent cause of primary renal disease, and clarifying the pathogenesis of IgAN is of great importance for its diagnosis and treatment. It is well known that Mycobacterium tuberculosis (MTB) can infect the urinary tract and result in the typical symptoms of cystitis. However, MTB can also affect the kidney more insidiously. Patients may present with glomerular disease, and sometimes with advanced renal failure. This study was to investigate the association between MTB infection and IgA nephropathy (IgAN), and the early diagnosis of MTB-mediated IgAN by means of early secreted antigenic target 6 (ESAT-6) detection in renal biopsies...
January 30, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28134679/pathogenic-mechanisms-of-intracellular-bacteria
#13
Hans Helmut Niller, Roland Masa, Annamária Venkei, Sándor Mészáros, Janos Minarovits
PURPOSE OF REVIEW: We wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. Reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread. RECENT FINDINGS: DNA-(cytosine C5)-methyltransferases of Mycoplasma hyorhinis targeting cytosine-phosphate-guanine (CpG) dinucleotides and a Mycobacterium tuberculosis methyltransferase targeting non-CpG sites methylated the host cell DNA and altered the pattern of gene expression...
January 27, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28125665/deregulated-lncrnas-in-b-cells-from-patients-with-active-tuberculosis
#14
Yurong Fu, Xianqin Xu, Junfang Xue, Wenping Duan, Zhengjun Yi
Role of lncRNAs in human adaptive immune response to TB infection is largely unexplored. To address this issue, here we characterized lncRNA expression profile in primary human B cell response to TB infection using microarray assay. Several lncRNAs and mRNAs were chosen for RT-qPCR validation. Bioinformatics prediction was applied to delineate function of the deregulated mRNAs. We found that 844 lncRNAs and 597 mRNAs were differentially expressed between B cell samples from individuals with or without TB. KEGG pathway analysis for the deregulated mRNAs indicated a number of pathways, such as TB, TLR signaling pathway and antigen processing and presentation...
2017: PloS One
https://www.readbyqxmd.com/read/28122644/mtb-specific-lymphocyte-responses-are-impaired-in-tuberculosis-patients-with-pulmonary-cavities
#15
Jun Wang, Yaping Dai, Jun Liu, Yongmei Yin, Hao Pei
OBJECTIVE: Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB), is a global health problem. Because the failing immune response in the lung can lead to formation of a pulmonary cavity, this study was designed to clarify MTB-specific lymphocyte responses in TB patients with pulmonary cavities. METHODS: We utilized culture filtrate protein 10 (CFP-10) and early secretory antigenic target 6 (ESAT-6) as immunogenic MTB antigens following overnight stimulation of peripheral blood mononuclear cells (PBMCs)...
January 26, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28119750/mycobacterium-tuberculosis-esat6-and-cpf10-induce-adenosine-deaminase-2-mrna-expression-in-monocyte-derived-macrophages
#16
Mi Jung Bae, Suyeon Ryu, Ha-Jeong Kim, Seung Ick Cha, Chang Ho Kim, Jaehee Lee
BACKGROUND: Delayed hypersensitivity plays a large role in the pathogenesis of tuberculous pleural effusion (TPE). Macrophages infected with live Mycobacterium tuberculosis (MTB) increase the levels of adenosine deaminase2 (ADA2) in the pleural fluid of TPE patients. However, it is as yet unclear whether ADA2 can be produced by macrophages when challenged with MTB antigens alone. This study therefore evaluated the levels of ADA2 mRNA expression, using monocyte-derived macrophages (MDMs) stimulated with MTB antigens...
January 2017: Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28118809/involvement-of-protoporphyrin-ix-accumulation-in-the-pathogenesis-of-isoniazid-rifampicin-induced-liver-injury-the-prevention-of-curcumin
#17
Leiyan He, Yaoxue Guo, Ye Deng, Chun Li, Chengzi Zuo, Wenxing Peng
Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR-humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively...
February 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28117761/phloretin-exerts-anti-tuberculosis-activity-and-suppresses-lung-inflammation
#18
Dasom Jeon, Min-Cheol Jeong, Hum Nath Jnawali, Chulhee Kwak, Sungwon Ryoo, In Duk Jung, Yangmee Kim
An increase in the prevalence of the drug-resistant Mycobacteria tuberculosis necessitates developing new types of anti-tuberculosis drugs. Here, we found that phloretin, a naturally-occurring flavonoid, has anti-mycobacterial effects on H37Rv, multi-drug-, and extensively drug-resistant clinical isolates, with minimum inhibitory concentrations of 182 and 364 μM, respectively. Since Mycobacteria cause lung inflammation that contributes to tuberculosis pathogenesis, anti-inflammatory effects of phloretin in interferon-γ-stimulated MRC-5 human lung fibroblasts and lipopolysaccharide (LPS)-stimulated dendritic cells were investigated...
January 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28108375/the-role-of-pattern-recognition-receptors-in-lung-sarcoidosis
#19
Esmaeil Mortaz, Ian M Adcock, Atefhe Abedini, Arda Kiani, Mehdi Kazempour-Dizaji, Masoud Movassaghi, Johan Garssen
Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs)...
January 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28092373/chronic-signaling-via-the-metabolic-checkpoint-kinase-mtorc1-induces-macrophage-granuloma-formation-and-marks-sarcoidosis-progression
#20
Monika Linke, Ha Thi Thanh Pham, Karl Katholnig, Thomas Schnöller, Anne Miller, Florian Demel, Birgit Schütz, Margit Rosner, Boris Kovacic, Nyamdelger Sukhbaatar, Birgit Niederreiter, Stephan Blüml, Peter Kuess, Veronika Sexl, Mathias Müller, Mario Mikula, Wolfram Weckwerth, Arvand Haschemi, Martin Susani, Markus Hengstschläger, Michael J Gambello, Thomas Weichhart
The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo...
March 2017: Nature Immunology
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