Shared signaling pathways and comprehensive therapeutic approaches among diabetes complications

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 8, 2025

The growing global prevalence of diabetes mellitus (DM), along with its associated complications, continues to rise. When clinically detected most DM complications are irreversible. It is therefore crucial detect and address these early systematically in order improve patient care outcomes. current clinical practice often prioritizes by addressing one complication while overlooking others that could occur. proposed the commonly targeted cell types including vascular cells, immune glial fibroblasts mediate might share responses diabetes. In addition, impact be influenced other complications. Recognizing focusing on shared among impacted cellular constituents, will allow simultaneously all DM-related limit adverse treatment impacts. This review explores understanding pathological signaling mechanisms recognizes new concepts benefit from further investigation both basic settings. ultimate goal develop more comprehensive strategies, which effectively multiple organs

Язык: Английский

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IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(13), С. 4181 - 4203

Опубликована: Янв. 1, 2023

The effective approach to discover innovative drugs will ask natural products for answers because of their complex and changeable structures multiple biological activities.Inhibitory kappa B kinase beta (IKKβ), known as IKK2, is a key regulatory responsible the activation NF-κB through its phosphorylation at Ser177 Ser181 promote inhibitors (IκBs), triggering ubiquitination degradation active nuclear factor kappa-B (NF-κB) cascade.Chemical inhibition IKKβ or genetic knockout has become an method block NF-κB-mediated proliferation migration tumor cells inflammatory response.In this review, we summarized structural feature transduction mechanism discovery from resources (e.g.sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, alkaloids) chemical synthesis (e.g.pyrimidines, pyridines, pyrazines, quinoxalines, thiophenes, thiazolidines).In addition, biosynthetic pathway novel potentials were discussed.This review provide inspiration modification based on skeleton further phytochemistry investigations.

Язык: Английский

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Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses

EMBO Molecular Medicine, Год журнала: 2023, Номер 15(5)

Опубликована: Март 10, 2023

Abstract Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin‐like kinase 1 (DCLK1), microtubule‐associated protein kinase, involved in neurogenesis human cancers. However, the role of DCLK1 atherosclerosis remains undefined. In this study, we identified upregulated macrophages atherosclerotic lesions ApoE −/− mice fed an HFD determined that macrophage‐specific deletion attenuates by reducing inflammation mice. Mechanistically, RNA sequencing analysis indicated mediates oxLDL‐induced via NF‐κB signaling pathway primary macrophages. Coimmunoprecipitation followed LC–MS/MS IKKβ as binding DCLK1. We confirmed directly interacts phosphorylates at S177/181, thereby facilitating subsequent activation gene expression Finally, pharmacological inhibitor prevents progression both vitro vivo. Our findings demonstrated macrophage promotes to activating IKKβ/NF‐κB. This study reports new regulator potential therapeutic target for atherosclerosis.

Язык: Английский

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Identification of critical endoplasmic reticulum stress-related genes in advanced atherosclerotic plaque

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 15, 2025

Atherosclerosis (AS) is the principal pathological cause of atherosclerotic cardiovascular diseases. Chronic endoplasmic reticulum stress (ERS) has been implicated in AS aetiopathogenesis, but underlying molecular interactions remain unclear. This study aims to identify mechanisms ERS pathogenesis inform innovative diagnostic approaches and therapeutic targets for managing AS. GSE28829 GSE43292—human early advanced carotid tissue samples—were obtained from Gene Expression Omnibus database. Endoplasmic stress-related genes (ERSRGs) were GeneCards. Differential gene expression weighted co-expression network analyses conducted associated with atherosclerosis, intersection ER-related revealed three ERSRGs (i.e. CTSB, LYN, CYBB) plaque. These exhibited associations various immune cells. Additionally, upregulated human tissues, mouse models progressive lesions, vitro macrophage models. In conclusion, this identified CYBB as potentially critical plaque, demonstrating their good utility offering novel insights into potential pathobiology progression, paving way exploring targets.

Язык: Английский

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Roles of pyroptosis in atherosclerosis pathogenesis

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115369 - 115369

Опубликована: Авг. 27, 2023

Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin protein-mediated membrane pore formation, swelling, and rapid lysis. Recent studies have suggested that pyroptosis closely related to atherosclerosis (AS). Previous reported involving endothelial cells (ECs), macrophages, smooth muscle (SMCs) plays an important role in the formation development AS. not only causes local inflammation but also amplifies inflammatory response it aggravates plaque instability, leading rupture thrombosis, eventually resulting acute cardiovascular events. In this review, we clarified some novel pathways mechanics presented potential drugs.

Язык: Английский

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Natural product/diet-based regulation of macrophage polarization: Implications in treatment of inflammatory-related diseases and cancer

The Journal of Nutritional Biochemistry, Год журнала: 2024, Номер 130, С. 109647 - 109647

Опубликована: Апрель 10, 2024

Язык: Английский

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Tremella fuciformis Berk Alleviated Atherosclerosis Symptoms via Nuclear Factor-Kappa B-Mediated Inflammatory Response in ApoE−/− Mice

Nutrients, Год журнала: 2024, Номер 17(1), С. 160 - 160

Опубликована: Дек. 31, 2024

Background: Atherosclerosis, a persistent inflammatory disease marked by the presence of atherosclerotic plaques or fibrous plaques, is significant contributor to onset development cardiovascular disease. Tremella fuciformis Berk contains various active ingredients that have anti-inflammatory, antioxidant, and hypolipidemic properties. Nevertheless, potential effects T. on atherosclerosis not been systematically reported. Method: In this study, ApoE−/− mice were employed as models caused high-fat diet (HFD) investigate effect fuciformis. Gut microbiota serum metabolism analysis performed elucidate mechanism for its anti-atherosclerosis effects. Results: significantly decreased aortic root wall thickness area lipid droplets, regulated levels, inhibited fat accumulation improve lesions. Furthermore, altered metabolite (including diethyl phthalate succinate) abundance microbiota, such Coriobacteriaceae_UCG-002 Alistipes, suppressed response ameliorate via nuclear factor-kappa B (NF-κB)-mediated in HFD-induced mice. Conclusions: These results offer theoretical basis data support strategy treating atherosclerosis.

Язык: Английский

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Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

Egyptian Journal of Medical Human Genetics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 4, 2025

Abstract Background Huntington's disease (HD) could cause progressive motor deficits, psychiatric symptoms, and cognitive impairment. With the increasing use of pharmacotherapies theoretically target neurotransmitters, incidence HD is still not decreasing. However, molecular pathogenesis have been illuminate. It momentous to further examine HD. Methods The next generation sequencing dataset GSE105041 was downloaded from Gene Expression Omnibus (GEO) database. Using DESeq2 in R bioconductor package screen differentially expressed genes (DEGs) between samples normal control samples. ontology (GO) term REACTOME pathway enrichment were performed on DEGs. Meanwhile, using Integrated Interactions Database (IID) database Cytoscape software construct protein–protein interaction (PPI) network module analysis, identify hub with highest value node degree, betweenness, stress closeness scores. miRNA-hub gene regulatory TF-hub constructed analyzed. Receiver operating characteristic curves analysis for diagnostic genes. Results We identified 958 DEGs, consisting 479 up regulated DEGs down GO terms analyses by g:Profiler online results revealed that mainly enriched multicellular organismal process, developmental signaling GPCR MHC class II antigen presentation. Network Analyzer plugin PPI network, LRRK2, MTUS2, HOXA1, IL7R, ERBB3, EGFR, TEX101, WDR76, NEDD4L COMT selected as Hsa-mir-1292-5p, hsa-mir-4521, ESRRB SREBF1 are potential biomarkers predicted be associated Conclusion This study investigated key pathways interactions its complications, which might help reveal correlation complications. current investigation captured prediction, follow-up biological experiments enforced validation.

Язык: Английский

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DCLK1 in gastrointestinal cancer: A driver of tumor progression and a promising therapeutic target

International Journal of Cancer, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Cancers of the gastrointestinal (GI) tract, including colorectal, pancreatic, and hepatocellular carcinomas, represent a significant global health burden due to their high incidence mortality rates. Doublecortin-like kinase 1 (DCLK1), initially identified for its role in neurogenesis, has emerged as crucial player GI cancer progression. This review comprehensively examines multifaceted roles DCLK1 cancers, focusing on structural isoforms, functions normal inflammatory states, contributions progression metastasis. is overexpressed various cancers associated with poor prognosis, enhanced tumorigenic potential, increased metastatic capacity. The discusses molecular mechanisms through which influences stem cell maintenance, epithelial-mesenchymal transition (EMT), survival pathways, well interactions key signaling pathways such Notch, WNT/β-catenin, NF-κB. potential therapeutic target also explored, highlighting preclinical early clinical efforts inhibit function using small molecule inhibitors or monoclonal antibodies. Despite advancements, further research needed fully elucidate DCLK1's develop effective strategies targeting this protein.

Язык: Английский

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Epigenetic upregulation of CLEC5A contributes to monocyte/macrophage dysfunction in coronary artery disease

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142471 - 142471

Опубликована: Март 1, 2025

Язык: Английский

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