Pyroptosis in health and disease: mechanisms, regulation and clinical perspective

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

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Mechanism of TGIF1 on glycolipid metabolism disorders in mice with type 2 diabetes

BMJ Open Diabetes Research & Care, Journal Year: 2025, Volume and Issue: 13(1), P. e004509 - e004509

Published: Jan. 1, 2025

Introduction Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency insulin. This study aims to explore mechanism TGFB-induced factor homeobox 1 (TGIF1) in glycolipid metabolism mice with T2D. Research design and methods Mice T2D were induced high-fat diet low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed T2D, weight monitored. The fasting plasma glucose, serum insulin, triglycerides, total cholesterol, low-density lipoprotein high-density cholesterol measured. Staining assays performed observe liver tissue pathology lipid accumulation. Liver function oxidative stress Palmitic acid (PA)-induced primary hepatocytes used establish cell models. cells, viability, cellular uptake consumption, intracellular glycogen content detected. expression TGIF1, miR-106b-5p, early growth response (EGR2) detected their binding relationships analyzed. Combined experiments conducted validate mechanism. Results downregulated overexpression reduced hyperglycemia hyperlipidemia, improved insulin resistance, increased content, attenuated accumulation disorders enriched on miR-106b-5p promoter promoted expression. inhibited EGR2 inhibition or partially reversed alleviative effect disorders. Conclusion reduces through miR-106b-5p/EGR2 axis.

Language: Английский

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Differential Pattern of Circulating MicroRNA Expression in Patients with Intracranial Atherosclerosis

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 514 - 514

Published: Feb. 19, 2025

Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial distinct from ICAS, which may explain the clinical variability as well. Methods: chose number miRNAs involved in various steps atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) examined their plasma levels cohort patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 had ICAS). Results: A differential pattern circulating miR expression was found patients: there an overexpression miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, miR-126-3p. The following miRs were underexpressed intracranial atherosclerosis-miR-712/205-3p miR-100-3p. These changes represent plethora atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), leukocyte recruitment (miR-126). In symptomatic patients, we observed statistically significant upregulation miR-712/205-3p miR-146a-5p. Conclusions: Overall, findings our pilot study revealed several new interesting associations: (1) seems have different profile (regarding microRNA expression) than isolated vessel involvement; (2) stroke be potentiated by other pathophysiologic mechanisms extracranial-only (ECAS). Certain (e.g., miR-712/205) seem larger impact on atherosclerosis; this potentially linked difference between extra- artery morphology physiology, lead said differences. This underscores importance making distinction future ECAS likely vary.

Language: Английский

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Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103321 - 103321

Published: Aug. 19, 2024

Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.

Language: Английский

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The dance of macrophage death: the interplay between the inevitable and the microenvironment

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

Published: March 20, 2024

Macrophages are highly plastic cells ubiquitous in various tissues, where they perform diverse functions. They participate the response to pathogen invasion and inflammation resolution following immune response, as well maintenance of homeostasis proper tissue generally considered long-lived with relatively strong resistance numerous cytotoxic factors. On other hand, their death seems be one principal mechanisms by which macrophages physiological functions or can contribute development certain diseases. In this review, we scrutinize three distinct pro-inflammatory programmed cell pathways - pyroptosis, necroptosis, ferroptosis occurring under specific circumstances, explain how these appear undergo dynamic yet not always final changes before ultimately dying. We achieve that examining interconnectivity types, seem create a coordinated flexible system responding microenvironment. Finally, discuss complexity consequences pyroptotic, necroptotic, ferroptotic pathway induction two pathological conditions atherosclerosis cancer. summarize damage-associated molecular patterns (DAMPs) along microenvironmental factors, macrophage polarization states, associated general outcomes, such comprehensive look at correlations may point out methodologies potential therapeutic approaches.

Language: Английский

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Genome-wide transcriptional profiling and functional analysis of long noncoding RNAs and mRNAs in chicken macrophages associated with the infection of avian pathogenic E. coli

BMC Veterinary Research, Journal Year: 2024, Volume and Issue: 20(1)

Published: Feb. 7, 2024

Abstract Background Avian pathogenic E. coli (APEC) can cause localized or systemic infections, collectively known as avian colibacillosis, resulting in huge economic losses to poultry industry globally per year. In addition, increasing evidence indicates that long non-coding RNAs (lncRNAs) play a critical role regulating host inflammation response bacterial infection. However, the of lncRNAs APEC infection remains unclear. Results Here, we found 816 differentially expressed (DE) and 1,798 DE mRNAs infected chicken macrophages by RNAseq. The identified lncRNA-mRNAs were involved Toll like receptor signaling pathway, VEGF fatty acid metabolism, phosphatidylinositol system, other types O-glycan biosynthesis. Furthermore, novel lncRNA TCONS_00007391 an important immune regulator was able regulate inflammatory directly targeting CD86 . Conclusion These findings provided better understanding also offered potential drug targets for therapy development against

Language: Английский

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Astaxanthin-loaded polylactic acid-glycolic acid nanoparticles alleviates atherosclerosis by suppressing macrophage ferroptosis via the NRF2/SLC7A11/GPX4 pathway.

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: 765, P. 110316 - 110316

Published: Jan. 22, 2025

Language: Английский

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Innovative Approaches in Atherosclerosis Treatment: Harnessing Traditional Chinese Medicine to Target Long Non-Coding RNAs

Phytomedicine, Journal Year: 2025, Volume and Issue: 139, P. 156488 - 156488

Published: Feb. 9, 2025

Language: Английский

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Therapeutic Advances in Peripheral Nerve Injuries: Nerve-Guided Conduit and Beyond

Tissue Engineering Part B Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Peripheral nerve injury (PNI), a challenging neurosurgery issue, often leads to partial or complete loss of neuronal functions and even neuropathic pain. Thus far, the gold standard for treating peripheral deficit remains autografts. While numerous reviews have explored PNI regeneration, this work distinctively synthesizes recent advancements in tissue engineering-particularly four-dimensional (4D) bioprinting exosome therapies-with an emphasis on their clinical translation. By consolidating findings spanning molecular mechanisms therapeutic applications, review proposes actionable framework advancing experimental strategies toward clinically viable solutions. Our critically evaluates emerging innovations such as dynamically adaptive 4D-printed conduits exosome-based therapies, underscoring potential match conventional autografts achieving functional restoration. Impact Statement Although several previous been made describing with great detail degenerative regenerative nervous systems, well existing exploratory treatment strategies, we focus more latest each those topics.

Language: Английский

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Structural optimization and pharmacological evaluation of diphenyl amine esters as anti-hepatocellular carcinoma agents by targeting TAR RNA-Binding Protein 2

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117676 - 117676

Published: April 1, 2025

Language: Английский

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