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https://www.readbyqxmd.com/read/28636635/microrna-144-3p-inhibits-autophagy-activation-and-enhances-bacillus-calmette-gu%C3%A3-rin-infection-by-targeting-atg4a-in-raw264-7-macrophage-cells
#1
Le Guo, Linlin Zhou, Qian Gao, Aijun Zhang, Jun Wei, Dantong Hong, Yuankui Chu, Xiangguo Duan, Ying Zhang, Guangxian Xu
MicroRNAs (miRNAs) are small noncoding nucleotides that play major roles in the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M. tuberculosis). Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection is largely unknown. In the present study, we demonstrate that Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection of macrophages leads to increased expression of miR-144-3p, which targets autophagy-related gene 4a (ATG4a), to inhibit autophagy activation and antimicrobial responses to BCG...
2017: PloS One
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#2
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636418/dxs-as-a-target-for-structure-based-drug-design
#3
Robin Matthias Gierse, Eswar Redeem, Eleonora Diamanti, Carsten Wrenger, Matthew R Groves, Anna Kh Hirsch
In this review, we analyze the enzyme DXS, the first and rate-limiting protein in the methylerythritol 4-phosphate pathway. This pathway was discovered in 1996 and is one of two known metabolic pathways for the biosynthesis of the universal building blocks for isoprenoids. It promises to offer new targets for the development of anti-infectives against the human pathogens, malaria or tuberculosis. We mapped the sequence conservation of 1-deoxy-xylulose-5-phosphate synthase on the protein structure and analyzed it in comparison with previously identified druggable pockets...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#4
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635627/molecular-quantum-similarity-chemical-reactivity-and-database-screening-of-3d-pharmacophores-of-the-protein-kinases-a-b-and-g-from-mycobacterium-tuberculosis
#5
Alejandro Morales-Bayuelo
Mycobacterium tuberculosis remains one of the world's most devastating pathogens. For this reason, we developed a study involving 3D pharmacophore searching, selectivity analysis and database screening for a series of anti-tuberculosis compounds, associated with the protein kinases A, B, and G. This theoretical study is expected to shed some light onto some molecular aspects that could contribute to the knowledge of the molecular mechanics behind interactions of these compounds, with anti-tuberculosis activity...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635184/design-synthesis-and-biological-evaluation-of-isothiosemicarbazones-with-antimycobacterial-activity
#6
Eva Novotná, Karel Waisser, Jiří Kuneš, Karel Palát, Lenka Skálová, Barbora Szotáková, Vladimír Buchta, Jiřina Stolaříková, Vít Ulmann, Marcela Pávová, Jan Weber, Jitka Komrsková, Pavlína Hašková, Ivan Vokřál, Vladimír Wsól
A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 μmol/L than 3-nitropropionic acid, a standard inhibitor...
June 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28634555/a-rare-case-of-pneumopericardium-in-the-setting-of-tuberculous-constrictive-pericarditis
#7
Lauro L Abrahan Iv, Stephanie Martha O Obillos, Jaime Alfonso M Aherrera, Jose Donato A Magno, Celia Catherine C Uy-Agbayani, Ulysses King G Gopez, Jobelle Joyce Anne R Baldonado
A 28-year-old Filipino male was admitted due to high-grade fevers and dyspnea on a background of chronic cough and weight loss. Due to clinical and echocardiographic signs of cardiac tamponade, emergency pericardiocentesis was performed on his first hospital day. Five days after, chest radiographs showed new pockets of radiolucency within the cardiac shadow, indicative of pneumopericardium. On repeat echo, air microbubbles admixed with loculated effusion were visualized in the anterior pericardial space. Constrictive physiology was also supported by a thickened pericardium, septal bounce, exaggerated respiratory variation in AV valve inflow, and IVC plethora...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28634538/prevalence-and-clinical-impact-of-vitamin-d-deficiency-on-abdominal-tuberculosis
#8
Vishal Sharma, Harshal S Mandavdhare, Amit Kumar, Ravi Sharma, Naresh Sachdeva, Kaushal K Prasad, Surinder S Rana
BACKGROUND: Vitamin D is recognised to have multiple actions, including role in immune modulation. The prevalence and impact of vitamin D deficiency (VDD) in abdominal tuberculosis is unknown. METHODS: We report the prevalence and clinical impact of VDD in patients with abdominal tuberculosis. The patients were divided into two groups: VDD (<20 ng/ml) or vitamin D sufficient (VDS) (⩾20 ng/ml). Groups were compared for extent (abdominal alone or extra-abdominal also) of disease and pattern of involvement (intestinal, peritoneal or both) and inflammatory response [serum C-reactive protein (CRP)]...
May 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#9
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#10
Nicholas C Harris, Michio Sato, Nicolaus A Herman, Frederick Twigg, Wenlong Cai, Joyce Liu, Xuejun Zhu, Jordan Downey, Ryan Khalaf, Joelle Martin, Hiroyuki Koshino, Wenjun Zhang
A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28633712/use-of-inhaled-corticosteroids-for-obstructive-lung-disease-following-anti-tuberculosis-treatment
#11
Anthony D Harries, Serge Ade, Nguyen Binh Hoa, Srinath Satyanarayana, Ajay M V Kumar
No abstract text is available yet for this article.
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633709/primary-pulmonary-actinomycosis-a-retrospective-analysis-of-145-cases-in-mainland-china
#12
M Zhang, X-Y Zhang, Y-B Chen
OBJECTIVE: To improve our understanding of pulmonary actinomycosis. METHODS: A retrospective analysis of 145 cases in mainland China was conducted. RESULTS: The male:female ratio was 2.7:1. Mean age at diagnosis was 48 years (± 12). Main symptoms were cough (87.6%), expectoration (40%), blood-stained sputum (37.2%), fever (26.9%), chest pain (24.8%) and haemoptysis (16.6%). Eighty-eight (60.7%) patients had no underlying disease. Only five patients received a correct initial diagnosis; 60 patients were misdiagnosed with lung cancer, followed by pulmonary tuberculosis (TB) and lung abscess...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633707/qualitative-analysis-of-biological-tuberculosis-samples-by-an-electronic-nose-based-artificial-neural-network
#13
E I Mohamed, M A Mohamed, M H Moustafa, S M Abdel-Mageed, A M Moro, A I Baess, S M El-Kholy
OBJECTIVE: To apply an e-nose system for monitoring headspace volatiles in biological samples from Egyptian patients with active pulmonary tuberculosis (TB) and healthy controls (HCs) and compare them with standard sputum analysis. DESIGN: The study population comprised 260 (140 males, 120 females) newly diagnosed TB patients and 240 (120 males, 120 females) HCs matched by age and socio-economic level admitted to hospitals specialising in chest diseases in Alexandria, Behera, Giza and Damietta Governorates, Egypt...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633706/depression-and-risk-of-tuberculosis-a-nationwide-population-based-cohort-study
#14
K H Oh, H Choi, E J Kim, H J Kim, S I Cho
BACKGROUND: Studies on the association between depression and risk of tuberculosis (TB) are lacking. OBJECTIVE: To determine the association between depression and risk of TB. METHODS: From a nationwide database, patients with depression were identified to form the exposure cohort between 2003 and 2013. The control cohort comprised an equivalent number of subjects without any mood disorders, with each subject age- and sex-matched to a patient in the exposure cohort...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633705/household-food-insecurity-is-associated-with-low-interferon-gamma-levels-in-pregnant-indian-women
#15
A Vaidya, R Bhosale, P Sambarey, N Suryavanshi, S Young, V Mave, S Kanade, V Kulkarni, P Deshpande, U Balasubramanian, J Elf, N Gupte, A Gupta, J S Mathad
SETTING: Over 20% of tuberculosis (TB) cases during pregnancy occur in India. OBJECTIVE: To determine the association between household food insecurity and interferon-gamma (IFN-γ) levels in pregnancy. DESIGN: Pregnant women in India were administered the Household Food Insecurity Access Scale (HFIAS) questionnaire and underwent an IFN-γ release assay. Logistic regression was used to identify factors associated with food insecurity. RESULTS: Of 538 women, 60 (11%) had household food insecurity, 47 (78%) of which were moderate or severe food insecure...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633704/effect-of-brazil-s-conditional-cash-transfer-programme-on-tuberculosis-incidence
#16
J S Nery, L C Rodrigues, D Rasella, R Aquino, D Barreira, A W Torrens, D Boccia, G O Penna, M L F Penna, M L Barreto, S M Pereira
OBJECTIVE: To evaluate the impact of the Brazilian cash transfer programme (Bolsa Família Programme, BFP) on tuberculosis (TB) incidence in Brazil from 2004 to 2012. DESIGN: We studied tuberculosis surveillance data using a combination of an ecological multiple-group and time-trend design covering 2458 Brazilian municipalities. The main independent variable was BFP coverage and the outcome was the TB incidence rate. All study variables were obtained from national databases...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633703/tuberculosis-inequalities-and-socio-economic-deprivation-in-portugal
#17
D Apolinário, A I Ribeiro, E Krainski, P Sousa, M Abranches, R Duarte
OBJECTIVE: To analyse the geographical distribution of tuberculosis (TB) in Portugal and estimate the association between TB and socio-economic deprivation. METHODS: An ecological study at the municipality level using TB notifications for 2010-2014 was conducted. Spatial Bayesian models were used to calculate smoothed standardised notification rates, identify high- and low-risk areas and estimate the association between TB notification and the European Deprivation Index (EDI) for Portugal and its component variables...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633702/impact-of-isoniazid-preventive-therapy-on-the-evaluation-of-long-term-effectiveness-of-infant-mva85a-vaccination
#18
E W Bunyasi, A K K Luabeya, M Tameris, H Geldenhuys, H Mulenga, B S Landry, T J Scriba, B-M Schmidt, W A Hanekom, H Mahomed, H McShane, M Hatherill
SETTING: South Africa. OBJECTIVE: To evaluate the long-term effectiveness of infant modified vaccinia Ankara virus-expressing antigen 85A (MVA85A) vaccination against tuberculosis (TB). DESIGN: We analysed data from a double-blind randomised placebo-controlled Phase 2b MVA85A infant TB vaccine trial (2009-2012), with extended post-trial follow-up (2012-2014). Isoniazid preventive therapy (IPT) was provided by public health services according to national guidelines...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633701/management-of-child-mdr-tb-contacts-across-countries-in-the-who-european-region-a-survey-of-current-practice
#19
A Turkova, M Tebruegge, F Brinkmann, M Tsolia, F Mouchet, B Kampmann, J A Seddon
The World Health Organization European Region has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) in the world, resulting in many vulnerable children being exposed each year. Evidence for preventive therapy following MDR-TB exposure is limited and current guidance is conflicting. An internet-based survey was performed to determine clinical practice in this region. Seventy-two clinicians from 25 countries participated. Practices related to screening and decision-making were highly variable...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28633700/trends-in-drug-resistant-tuberculosis-after-the-implementation-of-the-dots-strategy-in-shenzhen-china-2000-2013
#20
L Zhu, Y-Z Yang, H-Y Guan, S-M Cheng, Y-Y Jin, W-G Tan, Q-F Wu, X-L Liu, M-G Zhao, Z-H Lu, Z-W Jia
SETTING: The DOTS strategy has been regarded as the most cost-effective way to stop the spread of tuberculosis (TB) since its launch by the World Health Organization. OBJECTIVE: To estimate the effects of DOTS by tracking long-term trends in multidrug-resistant TB (MDR-TB). DESIGN: A retrospective cohort study was conducted from 2000 to 2013 to analyse trends in resistance to anti-tuberculosis drugs and the effect of DOTS-based treatment in Shenzhen, China, using the χ2 test...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
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