Punicalagin Ameliorates Diabetic Liver Injury by Inhibiting Pyroptosis and Promoting Autophagy via Modulation of the FoxO1/TXNIP Signaling Pathway

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: 68(12)

Published: June 1, 2024

Diabetic liver injury (DLI) is one of the complications diabetes mellitus, which seriously jeopardizes human health. Punicalagin (PU), a polyphenolic compound mainly found in pomegranate peel, has been shown to ameliorate metabolic diseases such as DLI, and mechanism needs be further explored. In this study, HFD/STZ-induced diabetic mouse model established investigate effect PU on DLI. The results show that intervention significantly improves histology serum biochemical abnormalities mice, inhibits expression pyroptosis-related proteins NLRP3, Caspase1, IL-1β, GSDMD up-regulated autophagy-related proteins. Meanwhile, treatment increases FoxO1 protein TXNIP mice. above are verified HepG2 cell induced by high glucose. AS1842856 specific inhibitor. combined with reverses regulatory effects pyroptosis autophagy cells. conclusion, study demonstrates may inhibit upregulate regulating FoxO1/TXNIP signaling, thereby alleviating

Language: Английский

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ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 4, 2023

To determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on thoracic aorta (TA) abdominal (AA) from angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model made significant findings: 1) Ang bypassed HFD-induced metabolic reprogramming induced stronger inflammation in AA than TA; 2) HFD upregulated 890 genes versus TA cytokine signaling; 3) 73 68 cytokines, scRNA-Seq identified markers macrophages immune cells, cell death regulators, respectively; transdifferentiation neuron, glial, squamous epithelial cells were by II-AA pyroptosis signaling with IL-1β caspase-4 more 4) Six transcriptomes patients AAA, AA, TA, additional models, PPE-AAA BAPN-Ang II-AAA, partially overlapped 10 lists new ER gene sets including 3 interaction protein regulators ATF6, PERK, IRE1, HPA localization genes, KEGG signal XBP1 transcription targets, ATF4 (PERK) ATF6 thapsigargin tunicamycin-ER 5) ROS MitoCarta immunity glycolysis genes; 6) Gene KO indicated that PERK played IRE1 promoting AAA whereas antioxidant NRF2 inhibited them. Our unprecedented ER-focused transcriptomic have provided novel insights as an organelle sensing various DAMPs initiating triggers II-accelerated differs susceptibilities aortas to diseases.

Language: Английский

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The role of pyroptosis in metabolism and metabolic disease

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116863 - 116863

Published: June 7, 2024

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation membrane pores mediated gasdermin protein family. Two main activation pathways have been documented: caspase-1-dependent canonical pathway caspase-4/5/11-dependent noncanonical pathway. leads to swelling, lysis, subsequent release inflammatory mediators, including interleukin-1β (IL-1β) interleukin-18 (IL-18). Chronic inflammation well-established foundation driver for development metabolic diseases. Conversely, dysregulation can also induce cellular pyroptosis. Recent studies highlighted significant role pyroptosis modulation in various diseases, type 2 diabetes mellitus, obesity, (dysfunction) associated fatty liver disease. These findings suggest that may serve as promising novel therapeutic target This paper reviews an in-depth study current advancements understanding progression

Language: Английский

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Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis

Redox Biology, Journal Year: 2023, Volume and Issue: 64, P. 102771 - 102771

Published: June 16, 2023

To identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened four tissues from ApoE

Language: Английский

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Pharmacological mechanisms of Ma Xing Shi Gan Decoction in treating influenza virus-induced pneumonia: intestinal microbiota and pulmonary glycolysis

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 5, 2024

Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in intestine and glycolysis lung tissues. In clinical guidelines for pneumonia treatment China, Ma Xing Shi Gan Decoction (MXSG) a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism action related to intestinal structure tissue glycolysis.

Language: Английский

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A new paradigm in intracellular immunology: Mitochondria emerging as leading immune organelles

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103331 - 103331

Published: Aug. 29, 2024

Mitochondria, traditionally recognized as cellular 'powerhouses' due to their pivotal role in energy production, have emerged multifunctional organelles at the intersection of bioenergetics, metabolic signaling, and immunity. However, understanding exact contributions immunity inflammation is still developing. This review first introduces innovative concept intracellular immunity, emphasizing how mitochondria serve critical immune signaling hubs. They are instrumental recognizing responding pathogen danger signals, modulating responses. We also propose leading organelles, drawing parallels with broader system functions antigen presentation, regulation, response. Our comprehensive explores mitochondrial pathways, therapeutic potential managing chronic diseases, discusses cutting-edge methodologies for research. Targeting a broad readership both experts newcomers field, this sets forth new directions that could transform our integrated organelles.

Language: Английский

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Effects of natural products on macrophage immunometabolism: a new frontier in the treatment of metabolic diseases

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107634 - 107634

Published: Jan. 1, 2025

Language: Английский

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FTO-associated osteoclastogenesis promotes alveolar bone resorption in apical periodontitis male rat via the HK1/USP14/RANK pathway

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 11, 2025

Alveolar bone resorption (ABR) is a key pathological manifestation in the development of apical periodontitis (AP) and contributes to AP-associated tooth loss among AP patients clinic. However, underlying mechanism ABR largely unknown. Here we show, total levels N6-methyladenosine (m6A) were reduced male rat alveolar tissues BMDM-derived osteoclasts (OC), which was associated with up-regulation obesity-associated protein (FTO). Subsequently FTO-mediated hexokinase (HK1) demethylation modification enhancing glycolytic pathway that stabilizes receptor activator NF-κB (RANK) via deubiquitination activity ubiquitin-specific protease 14 (USP14), further promotes osteoclastogenesis participate AP-related development. Finally, Dac51 (an FTO inhibitor) 2-DG HK1 both exhibit inhibitory osteoclastogenesis. Our current study reveals molecular on osteoclastogenesis-related provides therapeutic target modulating FTO/HK1/USP14/RANK axis. loss, whose Here, authors show

Language: Английский

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Bifidobacterium Adolescentis Prevent Diabetes Induced Liver Injury Via Pyroptosis Attenuation

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114518 - 114518

Published: March 1, 2025

Language: Английский

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Evaluation of the efficacy of cell-penetrating monoclonal antibodies targeting intracellular p-NLRP3S295 in alleviating hepatotoxicant-induced NAFLD

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142696 - 142696

Published: March 1, 2025

Language: Английский

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