Immune-endocrine crossroads: the impact of nuclear receptors in Tuberculosis and Chagas disease DOI Creative Commons
Ana Rosa Pérez, Óscar Bottasso, Natalia Santucci

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 7, 2025

Nuclear Receptors (NRs) comprise a superfamily of proteins with essential roles in cell signaling, survival, proliferation, and metabolism. They act as transcription factors are subclassified into families based on their ligands, DNA-binding sequences, tissue specificity, functions. Evidence indicates that infectious diseases, cancer, autoimmunity, NRs modulate immune endocrine responses, altering the transcriptional profile cells organs influencing disease progression. Chronic characterized by pathogen persistence, particularly notable for an exaggerated inflammatory process. Unlike acute inflammation, which helps host respond to pathogens, chronic inflammation leads metabolic disorders dysregulated neuro-immuno-endocrine response. Over time, disturbances cytokine, hormone, other compound production foster unbalanced, detrimental defensive This complexity underscores significant role ligand-dependent NRs. Tuberculosis Chagas Disease two critical infections. The causative agents, Mycobacterium tuberculosis Trypanosoma cruzi , have developed evasion strategies establish Their clinical manifestations associated disrupted immuno-endocrine pointing potential involvement review explores current understanding regulating immune-endocrine interactions within context Disease. These diseases remain global health concerns, developing countries, highlighting importance molecular mechanisms underlying host-pathogen mediated

Language: Английский

Steatotic liver disease, MASLD and risk of chronic kidney disease DOI Creative Commons
Josh Bilson, Alessandro Mantovani, Christopher D. Byrne

et al.

Diabetes & Metabolism, Journal Year: 2023, Volume and Issue: 50(1), P. 101506 - 101506

Published: Dec. 21, 2023

With the rising tide of fatty liver disease related to metabolic dysfunction worldwide, association this common with chronic kidney (CKD) has become increasingly evident. In 2020, more inclusive term dysfunction-associated (MAFLD) was proposed replace old nonalcoholic (NAFLD). 2023, a modified Delphi process led by three large pan-national associations. There consensus change nomenclature and definition include presence at least one five cardiometabolic risk factors as diagnostic criteria. The name chosen NAFLD steatotic (MASLD). from MAFLD then MASLD resulted in reappraisal epidemiological trends associations developing CKD. observed between MAFLD/MASLD CKD our understanding that can be an epiphenomenon linked underlying support notion individuals are substantially higher incident than those without MASLD. This narrative review provides overview literature on (a) evolution criteria for diagnosing highly prevalent disease, (b) evidence linking CKD, (c) mechanisms which (and strongly MASLD) may increase (d) potential drug treatments benefit both

Language: Английский

Citations

35
Functional and Structural Insights into the Human PPARα/δ/γ Targeting Preferences of Anti-NASH Investigational Drugs, Lanifibranor, Seladelpar, and Elafibranor DOI Creative Commons
S Kamata,

Akihiro Honda,

Ryo Ishikawa

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1523 - 1523

Published: July 29, 2023

No therapeutic drugs are currently available for nonalcoholic steatohepatitis (NASH) that progresses from fatty liver via oxidative stress-involved pathways. Three cognate peroxisome proliferator-activated receptor (PPAR) subtypes (PPARα/δ/γ) considered as attractive targets. Although lanifibranor (PPARα/δ/γ pan agonist) and saroglitazar (PPARα/γ dual under investigation in clinical trials NASH, the development of seladelpar (PPARδ-selective agonist), elafibranor (PPARα/δ many other dual/pan agonists has been discontinued due to serious side effects or little/no efficacies. This study aimed obtain functional structural insights into potency, efficacy, selectivity against PPARα/δ/γ three current past anti-NASH investigational drugs: lanifibranor, seladelpar, elafibranor. Ligand activities were evaluated by assays detect different facets PPAR activation: transactivation assay, coactivator recruitment thermal stability assay. Seven high-resolution cocrystal structures (namely, those PPARα/δ/γ-ligand-binding domain (LBD)-lanifibranor, PPARα/δ/γ-LBD-seladelpar, PPARα-LBD-elafibranor) obtained through X-ray diffraction analyses, six which represent first deposit Protein Data Bank. Lanifibranor found bind regions pockets activated all with potencies efficacies assays. In contrast, induced (not stability) subtypes, but PPARδ/γ-LBD-elafibranor cocrystals not obtained. These results illustrate highly variable activation profiles binding modes these ligands define their pharmacological actions.

Language: Английский

Citations

24
Exogenous hydrogen sulfide improves non-alcoholic fatty liver disease by inhibiting endoplasmic reticulum stress/NLRP3 inflammasome pathway DOI

Xiaodi Fu,

Qi Zhang, Yuhang Chen

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Language: Английский

Citations

1
Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status DOI Creative Commons

Chenglin Hu,

Yuan Chen, Xinpeng Yin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 13, 2025

Abstract The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion exocrine digestive enzymes. Complex interactions signaling mechanisms between functions of pancreas play a crucial role in maintaining metabolic homeostasis overall health. Compelling evidence indicates direct indirect crosstalk parts, influencing development diseases affecting both. From developmental perspective, parts share same origin—the “tip-trunk” domain. In certain circumstances, pancreatic cells may transdifferentiate into endocrine-like cells, insulin-secreting cells. Additionally, several diseases, including cancer, pancreatitis, diabetes, exhibit potential relevance to both functions. Endocrine communicate directly cytokines or indirectly regulating immune microenvironment. This affects onset progression these diseases. review summarizes history milestones findings related their embryonic development, phenotypic transformations, roles health disease, endocrine-exocrine from perspective therapeutic targets. Elucidating regulatory provide novel insights for understanding treatment

Language: Английский

Citations

1
Novel Thiazolones for the Simultaneous Modulation of PPARγ, COX-2 and 15-LOX to Address Metabolic Disease-associated Portal Inflammation DOI Creative Commons

Mai S. El-Shoukrofy,

Azza Ismail,

Reem H. Elhamammy

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117415 - 117415

Published: Feb. 22, 2025

Language: Английский

Citations

1
The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease DOI Creative Commons
Yu Zhang, Jiahui Yang, Jiali Min

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 25, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic worldwide, with a prevalence as high 32.4%. MASLD encompasses spectrum of pathologies, ranging from steatosis to metabolic steatohepatitis (MASH), fibrosis, and, in some cases, progression end-stage (cirrhosis and hepatocellular carcinoma). A comprehensive understanding pathogenesis this highly prevalent may facilitate identification novel targets for development improved therapies. E3 ubiquitin ligases deubiquitinases (DUBs) are key regulatory components ubiquitin‒proteasome system (UPS), which plays pivotal role maintaining intracellular protein homeostasis. Emerging evidence implicates that aberrant expression DUBs involved MASLD. Here, we review abnormalities by (1) discussing their targets, mechanisms, functions MASLD; (2) summarizing pharmacological interventions targeting these enzymes preclinical clinical studies; (3) addressing challenges future therapeutic strategies. This synthesizes current highlight strategies based on UPS progressive disease.

Language: Английский

Citations

1
Novel Therapeutic Approaches to Liver Fibrosis Based on Targeting Oxidative Stress DOI Creative Commons

Ana Blas‐García,

Nadezda Apostolova

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1567 - 1567

Published: Aug. 5, 2023

Chronic liver disease (CLD) constitutes a growing global health issue, with no effective treatments currently available. Oxidative stress closely interacts other cellular and molecular processes to trigger pathways in different hepatic cells fuel the development of fibrosis. Therefore, inhibition reactive oxygen species (ROS)-mediated effects modulation major antioxidant responses counteract oxidative stress-induced damage have emerged as interesting targets prevent or ameliorate injury. Although many preclinical studies shown that dietary supplements properties can significantly CLD progression animal models, this strategy has not proved reduce fibrosis when translated into clinical trials. Novel more specific therapeutic approaches are thus required alleviate We reviewed relevant literature concerning crucial role alterations redox homeostasis cell types during discussed current pharmacological by reducing focusing on selective enzymatic oxidant sources, systems ROS-mediated pathogenic processes.

Language: Английский

Citations

19
The global perspective on peroxisome proliferator-activated receptor γ (PPARγ) in ectopic fat deposition: A review DOI

Yanhao Qiu,

Mailin Gan, Xingyu Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 253, P. 127042 - 127042

Published: Sept. 23, 2023

Language: Английский

Citations

17
Inhibition of ferroptosis reverses heart failure with preserved ejection fraction in mice DOI Creative Commons
Yixiao Xiong, Xin Liu, Ling Jiang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 24, 2024

Abstract Background Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart cases. The molecular mechanisms by which HFpEF leads to impaired diastolic function the have not been clarified, nor drugs that target clinical symptoms patients. Methods chip data (GSE180065) was downloaded from National Center Biotechnology Information (NCBI) database. Differentially expressed genes (DEGs) were filtered limma package in R and processed GO KEGG pathway analyses. Then, ferroptosis-related identified taking intersection between DEGs genes. CytoHubba MCODE used screen hub protein–protein interaction (PPI) network. Establishment a mouse model validate transcript levels phenotypes. Transcript phenotypic changes hearts mice further examined after use ferroptosis inhibitors. Results enrichment analyses suggested significantly enriched pathways. A total 24 gene dataset DEGs. established PPI network analyzed modules, 11 obtained. In animal experiments, showed significant abnormal activation ferroptosis. expression trends associated ferroptosis, except Cdh1, consistent results bioinformatics analysis. Inhibition alters ameliorates Conclusions present study contributes deeper understanding specific is involved development suggests inhibition may mitigate progression HFpEF. addition, eleven recognized as potential drug binding targets.

Language: Английский

Citations

7
The gut-liver axis: emerging mechanisms and therapeutic approaches for nonalcoholic fatty liver disease and type 2 diabetes mellitus DOI
Monika Bhardwaj, Papiya Mitra Mazumder

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Language: Английский

Citations

7