Bird’s Eye View on Mycobacterium tuberculosis–HIV Coinfection: Understanding the Molecular Synergism, Challenges, and New Approaches to Therapeutics DOI

Siranjeevi Rangaraj,

Anushka Agarwal,

Sharmistha Banerjee

и другие.

ACS Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is the most common secondary infection in Human Immunodeficiency Virus (HIV) infected population, accounting for more than one-fourth of deaths people living with HIV (PLWH). Reciprocally, increases susceptibility to primary TB or reactivation latent several folds. The synergistic interactions between M.tb and not only potentiate their deleterious impact but also complicate clinical management both diseases. M.tb-HIV coinfected patients have a high risk failure accurate diagnosis, treatment inefficiency HIV, concurrent nontuberculous mycobacterial infections, other comorbidities such as diabetes mellitus, severe cytotoxicity due drug overburden, immune reconstitution inflammatory syndrome (IRIS). need hour understand coinfection biology collective on host immunocompetence think out-of-the-box perspectives, including host-directed therapy under rising view homeostatic medicines. This review aims highlight molecular players, from pathogens host, that facilitate host-associated proteins/enzymes regulating immunometabolism, underlining potential targets designing screening chemical inhibitors reduce burden concomitantly during coinfection. To appreciate necessity revisiting therapeutic approaches research priorities, we provide glimpse anti-TB antiretroviral drug-drug interactions, project gaps our understanding biology, enlist some key initiatives will help us deal epidemic

Язык: Английский

Targeting organ-specific mitochondrial dysfunction to improve biological aging DOI Creative Commons
Corina T. Madreiter‐Sokolowski, Ursula Hiden, Jelena Krstić

и другие.

Pharmacology & Therapeutics, Год журнала: 2024, Номер 262, С. 108710 - 108710

Опубликована: Авг. 22, 2024

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites key regulators programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, mitochondrial dysfunction pivotal factor progressive age-related decline cellular homeostasis organ function. The current review examines recent advances understanding interplay between organ-specific aging. Thereby, we dissect molecular mechanisms underlying impairment associated with deterioration exploring DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated patterns, biogenesis, turnover, dynamics. We also highlight emerging therapeutic preclinical clinical tests that supposed rejuvenate such as antioxidants, biogenesis stimulators, modulators turnover Furthermore, discuss potential benefits challenges use interventions, emphasizing need for approaches given unique characteristics different tissues. conclusion, this highlights addressing mitigate aging, focusing on skin, liver, lung, brain, skeletal muscle, well reproductive, immune, cardiovascular systems. Based comprehensive multifaceted roles mitochondria, innovative may be developed optimized biological promote healthy across diverse

Язык: Английский

Процитировано

11

GLUT1-mediated glucose import in B cells is critical for anaplerotic balance and humoral immunity DOI Creative Commons

Theresa E.H. Bierling,

Amelie Gumann,

Shannon R. Ottmann

и другие.

Cell Reports, Год журнала: 2024, Номер 43(2), С. 113739 - 113739

Опубликована: Фев. 1, 2024

Glucose uptake increases during B cell activation and antibody-secreting (ASC) differentiation, but conflicting findings prevent a clear metabolic profile at different stages of activation. Deletion the glucose transporter type 1 (GLUT1) gene in mature cells (GLUT1-cKO) results normal development, it reduces germinal center ASCs. GLUT1-cKO mice show decreased antigen-specific antibody titers after vaccination. In vitro, GLUT1-deficient impaired activation, whereas established plasmablasts abolish glycolysis, relying on mitochondrial activity fatty acids. Transcriptomics metabolomics reveal an altered anaplerotic balance Despite attempts to compensate for deprivation by increasing mass expression associated with tricarboxylic acid cycle, hexosamine synthesis, ASCs lack metabolites energy production respiration, limiting protein synthesis. We identify GLUT1 as critical player defining response humoral immunity.

Язык: Английский

Процитировано

10

Regulation of the NLRP3 inflammasome by autophagy and mitophagy DOI
Suman Gupta,

Suzanne L. Cassel,

Fayyaz S. Sutterwala

и другие.

Immunological Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 17, 2024

Summary The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives broad inflammatory response. primary initial mediators of this response are pro‐IL‐1β and pro‐IL‐18, both which in an inactive form. Formation activates caspase‐1, cleaves pro‐IL‐18 triggers formation gasdermin D pores. Gasdermin pores allow for secretion active IL‐1β IL‐18 initiating organism‐wide can be beneficial to host; however, if inappropriately activated it lead significant pathology. While components known, precise details assembly less well defined conflicting. Here, we discuss several proposed pathways inflammasome. We examine role subcellular localization reciprocal regulation autophagy. focus on roles mitochondria mitophagy activating regulating Finally, detail impact pathologic responses development manifestations pulmonary disease.

Язык: Английский

Процитировано

10

THE REGULATION OF CELL METABOLISM BY HYPOXIA AND HYPERCAPNIA DOI Creative Commons

Ben Reddan,

Eoin P. Cummins

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108252 - 108252

Опубликована: Фев. 1, 2025

Every cell in the body is exposed to a certain level of CO2 and O2. Hypercapnia hypoxia elicit stress signals influence cellular metabolism function. Both conditions exert profound yet distinct effects on metabolic pathways mitochondrial dynamics, highlighting need for cells adapt changes gaseous microenvironment. The interplay between hypercapnia signalling key dictating homeostasis as microenvironmental O2 levels are inextricably linked. Hypercapnia, characterized by elevated pCO₂, introduces adaptations within aerobic pathways, affecting TCA cycle flux, lipid, amino acid metabolism, OXPHOS ETC. Hypoxia, defined reduced oxygen availability, necessitates shift from anaerobic glycolysis sustain ATP production, process orchestrated stabilisation HIF-1α. Given that present both physiological cancerous microenvironments, how might coexistence function niches tumor microenvironment?

Язык: Английский

Процитировано

1

Triclosan-Mediated Metabolic Oxidative Stress-Triggered Cytoskeletal Alterations in Zebrafish Gills and Intestine: An Integrated Biomolecular and NMR-Based Metabolomics Study DOI
Owias Iqbal Dar,

Annadurai Vinothkanna,

Xiaosu Ke

и другие.

Journal of Hazardous Materials, Год журнала: 2025, Номер unknown, С. 138251 - 138251

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells DOI Creative Commons
Xiaojia He,

Lillie Barnett,

Jennifer Jeon

и другие.

Toxics, Год журнала: 2024, Номер 12(1), С. 67 - 67

Опубликована: Янв. 13, 2024

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical particle emission exposures during operation. Although the composition of 3D emissions varies depending on materials, little is known about impact that from different filament types may have respiratory underlying cellular mechanisms. In this study, we used an vitro exposure chamber system to deliver two popular 3D-printing types, acrylonitrile butadiene styrene (ABS) polylactic acid (PLA), directly human small airway epithelial cells (SAEC) cultured air–liquid interface Using a scanning mobility sizer (SMPS) optical (OPS), monitored particulate matter (PM) terms their size distribution, concentrations, calculated deposited doses. Elemental ABS PLA was assessed using electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, compared effects cell viability, inflammation, metabolism SAEC. Our results reveal that, although filaments emitted higher total concentration particles smaller particles, SAEC were exposed similar doses for each type. Conversely, had distinct elemental compositions, which likely responsible differential oxidative stress, release inflammatory mediators, changes metabolism. Specifically, while ABS- PLA-emitted both reduced viability glutathione levels SAEC, significantly greater effect relative emissions. Additionally, pro-inflammatory cytokines including IL-1β, MMP-9, RANTES increased due exposure. While IL-6 IL-8 stimulated scenarios, VEGF exclusively exposures. Notably, induced metabolic perturbation amino acids metabolism, as well redox-regulated pathways arginine, methionine, cysteine, vitamin B3 whereas caused fatty carnitine dysregulation. Taken together, these advance our mechanistic understanding 3D-printer-emissions-induced toxicity highlight role properties play mediating outcomes.

Язык: Английский

Процитировано

7

Remodeling of T-cell mitochondrial metabolism to treat autoimmune diseases DOI Creative Commons

Liyan Lin,

Ruyu Ren,

Qiao Xiong

и другие.

Autoimmunity Reviews, Год журнала: 2024, Номер 23(6), С. 103583 - 103583

Опубликована: Июнь 1, 2024

T cells are key drivers of the pathogenesis autoimmune diseases by producing cytokines, stimulating generation autoantibodies, and mediating tissue cell damage. Distinct mitochondrial metabolic pathways govern direction T-cell differentiation function rely on specific nutrients enzymes. Metabolic substrate uptake metabolism form foundational elements for activation, proliferation, differentiation, effector function, contributing to dynamic interplay between immunological signals in coordinating adaptive immunity. Perturbations availability enzyme activity may impair immunosuppressive fostering autoreactive responses disrupting immune homeostasis, ultimately disease pathogenesis. A growing body studies has explored how processes regulate diverse subsets such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), hepatitis (AIH), inflammatory bowel (IBD), psoriasis. This review describes coordination biology metabolism, including electron transport chain (ETC), oxidative phosphorylation, amino acid fatty one‑carbon metabolism. study elucidated intricate crosstalk programs, signal transduction pathways, transcription factors. summarizes potential therapeutic targets signaling diseases, providing insights future studies.

Язык: Английский

Процитировано

7

Mitochondria – the CEO of the cell DOI
Laurie Lee-Glover, Martin Picard, Timothy E. Shutt

и другие.

Journal of Cell Science, Год журнала: 2025, Номер 138(9)

Опубликована: Май 1, 2025

As we have learned more about mitochondria over the past decades, including their essential cellular roles and how altered mitochondrial biology results in disease, it has become apparent that they are not just powerplants pumping out ATP at whim of cell. Rather, dynamic information energy processors play crucial directing dozens processes behaviors. They provide instructions to enact programs regulate various operations, such as complex metabolic networks, signaling innate immunity, even control cell fate, dictating when cells should divide, differentiate or die. To help current future generations biologists incorporate dynamic, multifaceted nature assimilate modern discoveries into scientific framework, need a 21st century 'rebranding'. In this Opinion article, argue be considered 'Chief Executive Organelle' - CEO

Язык: Английский

Процитировано

1

Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer DOI Creative Commons

Tyler Sniegowski,

Devaraja Rajasekaran,

Souad R. Sennoune

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Окт. 6, 2023

Abstract Pancreatic ductal adenocarcinoma (PDAC) cells have a great demand for nutrients in the form of sugars, amino acids, and lipids. Particularly, acids are critical cancer growth and, as intermediates, connect glucose, lipid nucleotide metabolism. PDAC meet these requirements by upregulating selective acid transporters. Here we show that SLC38A5 (SN2/SNAT5), neutral transporter is highly upregulated functional cells. Using CRISPR/Cas9-mediated knockout SLC38A5, its tumor promoting role an vitro cell line model well subcutaneous xenograft mouse model. metabolomics RNA sequencing, significant reduction many substrates OXPHOS inactivation response to deletion. Experimental validation demonstrates inhibition mTORC1, glycolysis mitochondrial respiration KO cells, suggesting serious metabolic crisis associated with Since activators mTORC1 TCA cycle intermediates/precursors, speculate insufficiency possible link between deletion respiration, underlying mechanism attenuation. Overall, promotes PDAC, thereby identifying novel, hitherto unknown, therapeutic target PDAC.

Язык: Английский

Процитировано

15

Arginine promotes seed energy metabolism, increasing wheat seed germination at low temperature DOI Creative Commons
Jiayu Li, Zhiyuan Li,

Yangyang Tang

и другие.

The Crop Journal, Год журнала: 2024, Номер 12(4), С. 1185 - 1195

Опубликована: Июль 14, 2024

Low temperatures during germination inhibit seed growth, lead to small and weak seedlings, significantly reduce the wheat yield. Alleviating adverse effects of low temperature on is highly important for achieving high stable yields. In this study, Tongmai 6 (insensitive) Zhengmai 113 (sensitive), which have different low-temperature sensitivities were treated with germination. The transcriptome, metabolome physiological data revealed that decreased rate, downregulated expression a large number genes involved in regulating glycometabolism, inhibited carbon, nitrogen (especially amino acids) energy metabolism seeds. Arginine content increased at temperature, its increase low-temperature-tolerant variety was greater than sensitive variety. priming experiment showed treatment an appropriate concentration arginine improved rate. conversion starch soluble sugar under exogenous conditions, key metabolites increased, utilization ATP seeds increased. Taken together, by relieving inhibition carbon improving metabolism.

Язык: Английский

Процитировано

5