Increased phosphorylation of AMPKα1 S485 in colorectal cancer and identification of PKCα as a responsible kinase. DOI Creative Commons
Yan Zhou, Tingting Lei, Zhimin Tang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217418 - 217418

Published: Dec. 1, 2024

The present study attempts to examine the biological effect of phosphorylation AMPKα1 S485 and identify responsible kinase in colon cancer cells. Thus, our results showed that was increased colorectal specimens as compared with adjacent normal tissues, which inversely correlated T172. Our further revealed on plays a promoting role cell proliferation, colony formation, migration growth Xenograft tumor. Furthermore, we identified PKCα specific for S485. First, under basal condition, blunted by Gö6983, pan PKC inhibitor, but not Akt MK2206, although latter countered off insulin-stimulated phosphorylation. Second, enhanced PMA attenuated sgRNA PKCα, PKCγ PKCδ, neither siRNA Akt1. Third, suppressed shRNA PLCγ1. Fourth, ectopically expressing constitutively active mutant PKCγ. Finally, increase high glucose or palmitic acid almost completely abolished Gö6983. Altogether, data reinforced tumor suppressive function AMPK demonstrated is major S485, contributes one mechanisms underlying regulation cells response nutritional conditions.

Language: Английский

Glucose homeostasis controls N-acetyltransferase 10-mediated ac4C modification of HK2 to drive gastric tumorigenesis DOI Creative Commons
Qiang Wang, Mengmeng Li, Chen Chen

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(6), P. 2428 - 2450

Published: Jan. 20, 2025

Rationale: Abnormal metabolic states contribute to a variety of diseases, including cancer. RNA modifications have diverse biological functions and are implicated in cancer development, gastric (GC). However, the direct relationship between glucose homeostasis 4-acetylcytosine (ac4C) modification GC remains unclear. Methods: The prognostic value acetyltransferase NAT10 expression was evaluated human cohort. Additionally, preoperative PET/CT data from patients Micro-PET/CT imaging mice were employed assess metabolism. role investigated through various experiments, xenografts, organoids, conditional knockout (cKO) mouse model. underlying mechanisms examined using dot blotting, immunofluorescence staining, co-immunoprecipitation, high-throughput sequencing, among other techniques. Results: Glucose deprivation activates autophagy-lysosome pathway, leading degradation by enhancing its interaction with sequestosome 1 (SQSTM1)/microtubule-associated protein light chain 3 alpha (LC3) complex, ultimately resulting reduction ac4C modification. Furthermore, levels elevated tissues correlate poor prognosis. A strong correlation exists 18F-FDG uptake patients. drives glycolytic metabolism carcinogenesis vitro vivo. Mechanistically, stimulates at intersection coding sequence (CDS) 3' untranslated region (3'UTR) hexokinase 2 (HK2) mRNA, stability activating thereby driving tumorigenesis. Conclusion: Our findings highlight critical crosstalk epitranscriptome carcinogenesis. This finding offers potential strategy targeting NAT10/HK2 axis for treatment patients, especially those highly active

Language: Английский

Citations

1
Kajf Alleviated Colorectal Cancer Liver Metastasis by Reshaping the Gut Microbiota and Inhibiting M2-Like Macrophage Polarization DOI
Zongmei Zheng, Yizhao Du, Hua Jiang

et al.

Published: Jan. 1, 2025

Background: Colorectal cancer liver metastasis (CRLM) is one of the most devastated complications colorectal (CRC) and usually indicates a poor prognosis for CRC. The herbal formula Kang-Ai-Jing-Fang (KAJF) has been applied in clinical against CRC several decades, but its underlying mechanism still undetermined.Purpose: study aims to explore anti-metastatic effect KAJF on CRLM by manipulating gut microbiota inhibiting M2-like macrophage activation.Methods: were orally administrated model mice induced intrasplenic injection murine cells. Fecal transplantation (FMT) was verify role KAJF-reshaped intervention's inhibition CRLM. Network pharmacology molecular docking conducted identify core targets active compounds. 16s rRNA, untargeted liquid chromatograph mass spectrometer (LC-MS/MS) metabolomics transcriptomics performed depict structure, metabolites profile differential genes.Results: effectively inhibited restored dysbiosis upregulating abundance butyrate-producing (Lactobacillus, Bacteroides, Bifidobacterium), further FMT validated therapeutic effects KAJF-remodeled bacteria delay enrichment. Additionally, net analysis revealed that ingredients from such as quercetin, luteolin, beta-sitosterol are highly interacted with TNF, AKT1 TP53, respectively. What' more, it observed population F4/80+ CD206+ macrophages related cytokines (CCL17, CCL22, IL10, IL4, TGF etc.) downregulated after treatment, well reduction CD4+ T cells myeloid-derived suppressor (MDSCs), an increasement CD8+ cells.Conclusions: research demonstrated suppressed partially regulating microbial metabolites, polarization.

Language: Английский

Citations

0
Porcine pericardium crosslinked with POSS-PEG-CHO possesses weakened immunogenicity and anti-calcification property DOI Creative Commons
Xiaobo Yu,

Jingli Ding,

Yingjie He

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: unknown, P. 101677 - 101677

Published: March 1, 2025

Language: Английский

Citations

0
Synthesis and Anti‐Aging Activity Exploration of Cycloastragenol Derivatives DOI
Chen Wang,

Hai‐di Wu,

Xiaodong Mu

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(12)

Published: March 1, 2025

Abstract There has been limited research on the preparation of analogues cycloartane‐type sapogenols (9,19‐cyclolanostanes). Therefore, we decided to use cycloastragenol as a lead compound for structural modification. The semi‐synthetic derivatives were mainly obtained by reactions such oxidation, alkylation, acylation, and aldol reactions. In this study, synthesized 27 derivatives, 20 which novel compounds, evaluated their protective activity t‐BHP‐induced C2C12 cell growth inhibition anti‐aging activities. We found that most inhibited damage. And certain reduced formation ROS decreased production MDA induced t‐BHP. findings indicate these might be useful in treatment age‐related diseases.

Language: Английский

Citations

0
KAJF Alleviated Colorectal Cancer Liver Metastasis by Reshaping the Gut Microbiota and Inhibiting M2-like Macrophage Polarization DOI
Zongmei Zheng, Yizhao Du, Hua Jiang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156766 - 156766

Published: April 1, 2025

Language: Английский

Citations

0
New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis DOI Creative Commons

Hoon An,

Yerin Jang,

Jung-In Choi

et al.

Biomolecules & Therapeutics, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

AMP-activated protein kinase (AMPK) activators have garnered significant attention for their potential to prevent the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) into fibrosis and fundamentally improve function. The broad spectrum pathways regulated by AMPK makes them promising alternatives conventional replacement therapies limited pharmacological treatments currently available. In this study, we aim illustrate newly detailed multiple mechanisms MASLD based on multiple-hit hypothesis. This model posits that impaired lipid metabolism, combined with insulin resistance imbalance, initiates inflammatory cascades, gut dysbiosis, accumulation toxic metabolites, ultimately promoting accelerating irreversible hepatocellular carcinoma (HCC). plays a multifaceted protective role against these pathological conditions regulating several key downstream signaling pathways. It regulates biological effectors critical responses, such as SIRT1, Nrf2, mTOR, TGF-β, through complex interrelated mechanisms. Due intricate connections, AMPK's is pivotal in managing disorders. review, demonstrate specific roles its related Several agents directly activate binding agonists, while some others indirectly modulating upstream molecules, including adiponectin, LKB1, AMP: ATP ratio. As can target each stage progression, development offers immense expand therapeutic strategies diseases MASH, MASLD, fibrosis.

Language: Английский

Citations

2
Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation DOI Creative Commons
Z. Zhang, Jiawei Guo

Antioxidants, Journal Year: 2024, Volume and Issue: 14(1), P. 38 - 38

Published: Dec. 31, 2024

Oxidative stress plays a pivotal role in the pathogenesis and progression of cardiovascular diseases (CVDs). This review focuses on signaling pathways oxidative during development CVDs, delving into molecular regulatory networks underlying various disease stages, particularly apoptosis, inflammation, fibrosis, metabolic imbalance. By examining dual roles influences sex differences levels susceptibility, this study offers comprehensive understanding diseases. The integrates key findings from current research three ways. First, it outlines major CVDs associated with their respective pathways, emphasizing stress’s central pathology. Second, summarizes protective effects, mechanisms action, animal models antioxidants, offering insights future drug development. Third, discusses applications, advantages, limitations, potential targets gene therapy providing foundation for novel therapeutic strategies. These tables underscore systematic integrative nature while theoretical basis precision treatment CVDs. A contribution is differential effects across different stages addition to proposal innovative, multi-level intervention strategies, which open new avenues system.

Language: Английский

Citations

2
Increased phosphorylation of AMPKα1 S485 in colorectal cancer and identification of PKCα as a responsible kinase. DOI Creative Commons
Yan Zhou, Tingting Lei, Zhimin Tang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: unknown, P. 217418 - 217418

Published: Dec. 1, 2024

The present study attempts to examine the biological effect of phosphorylation AMPKα1 S485 and identify responsible kinase in colon cancer cells. Thus, our results showed that was increased colorectal specimens as compared with adjacent normal tissues, which inversely correlated T172. Our further revealed on plays a promoting role cell proliferation, colony formation, migration growth Xenograft tumor. Furthermore, we identified PKCα specific for S485. First, under basal condition, blunted by Gö6983, pan PKC inhibitor, but not Akt MK2206, although latter countered off insulin-stimulated phosphorylation. Second, enhanced PMA attenuated sgRNA PKCα, PKCγ PKCδ, neither siRNA Akt1. Third, suppressed shRNA PLCγ1. Fourth, ectopically expressing constitutively active mutant PKCγ. Finally, increase high glucose or palmitic acid almost completely abolished Gö6983. Altogether, data reinforced tumor suppressive function AMPK demonstrated is major S485, contributes one mechanisms underlying regulation cells response nutritional conditions.

Language: Английский

Citations

0