Skip to content

Structures and Small Molecule Inhibitors in Cellular and Animal Models

My WordPress Blog

Menu
  • Sample Page
Menu

Moreover, treatment of rapamycin, combined with isoniazid, promote sterile clearance and prevention of TB reactivation (Fatima et?al

Posted on December 12, 2021 by president2010

Moreover, treatment of rapamycin, combined with isoniazid, promote sterile clearance and prevention of TB reactivation (Fatima et?al., 2020). WHO, 2020). Autophagy functions as a cell-autonomous defensive pathway against intracellular Mtb (Gutierrez et?al., 2004; Kimmey et?al., 2015). After phagocytosis, a majority of Mtb resides in phagosome to escape the phagolysosomal acidification, but some of them access to cytosol and can be targeted by xenophagy (Watson et?al., 2012; Manzanillo et?al., 2013; Gomes and Dikic, 2014; Paik et?al., 2019). Chondroitin sulfate Indeed, a variety of agents triggering autophagy/xenophagy promote phagosomal maturation through autophagic capture of either intraphagosomal Mtb or cytosolic pathogens (Gupta et?al., 2016; Kim Y. S. et?al., 2019). In this Review, we outline the mechanisms underlying the effects of autophagy-based agents to enhance host defense against Mtb infection. In particular, we discuss the mechanisms and?signaling pathways (adenosine 5-monophosphate [AMP]-activated protein kinase [AMPK], mammalian target of rapamycin [mTOR] kinase, Wnt, transcription factor EB [TFEB], cathelicidins, inflammation, endoplasmic reticulum [ER] stress,?and autophagy-related genes [ATGs]) that would make autophagy-activating agents a potential host-directed therapeutic?(HDT) or alternative to current tuberculosis (TB) chemotherapeutics. Overview of Autophagy During Mycobacterial Infection Autophagy is a catabolic process of damaged cellular components to ensure cell survival and homeostasis (Glick et?al., 2010; Ryter et?al., 2013). There are three canonical autophagy pathwaysmacroautophagy, microautophagy, and chaperone-mediated autophagy, which differ in how the cargo is targeted and delivered to lysosomes (Glick et?al., 2010; Ryter et?al., 2013). Macroautophagy (hereafter referred to as autophagy) is activated by stress signals including starvation, hypoxia, and infections, and is characterized by the formation of double-membraned autophagosomes, which fuse with a lysosome to form an autolysosome, the site of cargo degradation (Glick et?al., 2010; Ryter et?al., 2013). Mtb has developed numerous strategies to avoid autophagic defense and manipulate host innate immunity (Jiao and Sun, 2019). For example, the ESX-1 system, Mtb suppresses the late-stage autophagy in human dendritic cells to escape dendritic cell-mediated immunity (Romagnoli et?al., 2012). The enhanced intracellular survival (Eis) gene of Mtb inhibits macrophage autophagy, at least partly mediated through suppression of c-Jun N-terminal kinase (JNK)-reactive oxygen species (ROS) signaling, in macrophages (Shin et?al., 2010a). Also, Mtb lipoprotein LprE inhibits autophagy and cathelicidin expression to favor bacterial replication during infection (Padhi et?al., 2019). In addition, virulent Mtb strains inhibit the recruitment of Rab7, the late endosomal/lysosomal protein, to the phagosomes, thereby escaping from phagosomal fusion with lysosomes (Chandra et?al., 2015; Chandra and Kumar, 2016). However, ATGs, except ATG5, in myeloid cells do not appear to be essential in the activation of host defense (Kimmey et?al., 2015). In addition, Mtb pathogens can epigenetically control host autophagy pathway through regulation of microRNAs (miRNAs) to favor mycobacterial replication in the host cells during infection (Batista et?al., 2020; Ruiz-Tagle et?al., 2020; Silwal NAV3 et?al., 2020). The miRNAs that are associated with pathogenesis of Mtb infection include miR-33/miR-33* (Ouimet et?al., 2016), miR-889 (Chen et?al., 2020), Chondroitin sulfate miR-18a (Yuan et?al., 2020), and miR-125a (Kim et?al., 2015), all of which are increased by Mtb infection; whereas others such as miR-26a (Sahu et?al., 2017) and miR-17-5p (Kumar et?al., 2016), both of which are decreased by Mtb infection. Numerous miRNAs that are involved in the regulation of autophagy in terms of host-pathogen interaction during Mtb infection have been extensively discussed elsewhere (Kim J. K. et?al., 2017; Sabir et?al., 2018; Yang and Ge, 2018; Silwal et?al., 2020; Sinigaglia et?al., 2020) and are not the focus of this Review. Thus, it remains to be fully characterized the exact mechanisms by which Mtb evade from host autophagic defense system, Chondroitin sulfate although several autophagy-activating drugs/agents are able to suppress Mtb growth and (Stanley et?al., 2014; Gupta et?al.,.

Recent Posts

  • To validate the grade of the computational modeling from the organic structures using the CDR variations, we assessed the modeled organic structures with regards to the effects of modeling uncertainties towards the results from the statistical analyses shown in Supplementary Fig
  • Change from baseline of visual functioning subscale in the thyroid-associated ophthalmopathy-specific quality of life level (GO-QOL)
  • Perhaps fine-tuned and targeted manipulations of nuclear receptor binding sites within promoters, enhancers and switch sites of the immunoglobulin loci will ultimately prove successful for the control and optimization of immunoglobulin expression
  • However, it really is worthwhile to remark that (a) the speed of MDR attacks in our people was considerably less than the main one reported in these research which (b) since only one 1 away of 3 situations of MDR-related septic shock was ICU-acquired, it’s possible which the administration of ivIgGAM in sufferers already admitted towards the ICU avoided their colonization and subsequent infection with these bacteria
  • To get this hypothesis, ibrutinib effectively reduced serum IgM at six months in every cases with clonal IgM (median reduction, 27% [IQR, 9%-39%];P=

Recent Comments

  1. A WordPress Commenter on Hello world!

Archives

  • May 2025
  • April 2025
  • March 2025
  • February 2025
  • January 2025
  • December 2024
  • November 2024
  • October 2024
  • September 2024
  • May 2023
  • April 2023
  • March 2023
  • February 2023
  • January 2023
  • December 2022
  • November 2022
  • October 2022
  • September 2022
  • August 2022
  • July 2022
  • June 2022
  • May 2022
  • April 2022
  • March 2022
  • February 2022
  • January 2022
  • December 2021
  • November 2021
  • October 2021
  • September 2021

Categories

  • Acetylcholine ??7 Nicotinic Receptors
  • Acetylcholine Nicotinic Receptors
  • Acyltransferases
  • Alpha1 Adrenergic Receptors
  • Angiotensin Receptors, Non-Selective
  • APJ Receptor
  • Calcium Channels
  • Carrier Protein
  • cMET
  • COX
  • DAT
  • Decarboxylases
  • Dipeptidyl Peptidase IV
  • DP Receptors
  • FFA1 Receptors
  • GlyR
  • H1 Receptors
  • HDACs
  • Hsp90
  • IGF Receptors
  • LXR-like Receptors
  • Miscellaneous Glutamate
  • Neurokinin Receptors
  • Nicotinic Acid Receptors
  • Nitric Oxide, Other
  • NO Synthase, Non-Selective
  • Non-selective Adenosine
  • Nucleoside Transporters
  • Opioid, ??-
  • Oxidative Phosphorylation
  • p70 S6K
  • PI 3-Kinase
  • Platelet-Activating Factor (PAF) Receptors
  • Potassium (KV) Channels
  • Potassium Channels, Non-selective
  • Prostanoid Receptors
  • Protein Ser/Thr Phosphatases
  • PTP
  • Retinoid X Receptors
  • Serotonin (5-ht1E) Receptors
  • Shp2
  • Sigma1 Receptors
  • Signal Transducers and Activators of Transcription
  • Sirtuin
  • Syk Kinase
  • T-Type Calcium Channels
  • Ubiquitin E3 Ligases
  • Ubiquitin/Proteasome System
  • Uncategorized
  • Urotensin-II Receptor
  • Vesicular Monoamine Transporters
© 2025 Structures and Small Molecule Inhibitors in Cellular and Animal Models | Powered by Minimalist Blog WordPress Theme