Elucidating the dual roles of apoptosis and necroptosis in diabetic wound healing: implications for therapeutic intervention

Burns & Trauma, Год журнала: 2025, Номер 13

Опубликована: Янв. 1, 2025

Abstract Wound healing is a complex and multistep biological process that involves the cooperation of various cell types. Programmed death, including apoptosis necrotizing apoptosis, plays crucial role in this process. Apoptosis, controlled orderly programmed death regulated by genes, helps eliminate unnecessary or abnormal cells maintain internal environmental stability. It also regulates functions contributes to development many diseases. In wound healing, essential for removing inflammatory forming scars. On other hand, necroptosis, another form has not been thoroughly investigated regarding its healing. This review explores changes specific groups during after an injury delves into potential underlying mechanisms. Furthermore, it briefly discusses possible mechanisms linking inflammation fibrosis By understanding relationship between investigating molecular involved regulation, new strategies clinical treatment may be discovered.

Язык: Английский

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S-propargyl-cysteine attenuates temporomandibular joint osteoarthritis by regulating macrophage polarization via Inhibition of JAK/STAT signaling

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 7, 2025

Abstract Background Temporomandibular joint osteoarthritis (TMJ-OA) is a disease characterized by cartilage degradation and synovial inflammation, with limited effective treatment currently. Synovial macrophage polarization pivotal in TMJ-OA progression, making it promising therapeutic aspect. This study investigated the effects of S-propargyl-cysteine (SPRC), an endogenous H2S donor, on its potential alleviating TMJ-OA. Methods A MIA-induced rat model LPS-stimulated RAW264.7 macrophages were employed to evaluate SPRC vivo vitro. TMJ bone analyzed via micro-CT histological methods, while markers expression assessed RT-qPCR, western blot, immunofluorescence. RNA sequencing was performed macrophages, JAK2/STAT3 signaling pathway validated using JAK2-specific inhibitor AG490. The direct primary condylar chondrocytes examined evaluating ECM synthesis degradation. Co-culture experiments further macrophage-chondrocyte interactions. Results significantly alleviated damage model, as demonstrated improved volume structure. reduced pro-inflammatory M1 infiltration enhanced anti-inflammatory M2 polarization. effectively inhibited JAK2/STAT3, leading reduction inflammatory markers, including TNF-α, IL-6, iNOS. revealed that SPRC-treated macrophage-conditioned medium chondrocyte metabolic activity restored integrity. Conclusions SPRC-modulated alleviates JAK/STAT downregulation, thereby reducing inflammation These findings position candidate for provide insights into novel strategies targeting synovium-cartilage crosstalk. Graphical abstract

Язык: Английский

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Recent advances in the role of gasotransmitters in necroptosis

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Язык: Английский

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Sustained-Release H₂S Nanospheres Regulate the Inflammatory Microenvironment of Wounds, Promote Angiogenesis and Collagen Deposition, and Accelerate Diabetic Wound Healing

ACS Applied Bio Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Diabetic wounds are blocked in the inflammatory stage, growth factors degraded, and blood vessels difficult to regenerate, leading continuous necrosis nonhealing of wound. Hydrogen sulfide (H2S) plays an important role pathophysiological process wound healing has a long history treating skin diseases. Although salt solution is preferred donor exogenous H2S, its rapid release rate, excess production, difficulty accurately controlling dose limit use. Herein, we developed H2S sustained-release nanospheres NaHS@MS@LP for treatment diabetic wounds. nanosphere was composed NaHS-loaded mesoporous silicon core DSPE-PEG liposome outer membrane. When were used treat rats, delivered into cells loaded NaHS slowly released through hydrolysis, participating all stages healing. In conclusion, regulated microenvironment by inducing transformation macrophages M2 type promoted angiogenesis collagen deposition accelerate rats. Our findings provide strategies chronic wounds, including but not limited

Язык: Английский

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MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase featured by kinase-like domain without catalytic activity. MLKL was originally discovered to be phosphorylated receptor-interacting 1/3, typically increase plasma membrane permeabilization, and disrupt the integrity, ultimately executing necroptosis. Recent evidence uncovers association of with diverse cellular organelles, including mitochondrion, lysosome, endosome, endoplasmic reticulum, nucleus. Thus, this review mainly focuses on regulatory functions, mechanisms, targets in organelles rather than necroptosis summarize medical significance multiple diseases. On basis, we conclude analyze current progress prospect for development MLKL-related drugs, from natural products, small-molecule chemical compounds, proteolysis-targeting chimera. This aimed propel as valid drug target discovery novel promote their further applications.

Язык: Английский

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Collagen-Based Nanoparticles as Drug Delivery System in Wound Healing Applications

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 11321 - 11341

Опубликована: Ноя. 1, 2024

Background: Conventional wound dressings often adhere to wounds and can cause secondary injury due their lack of anti-inflammatory antibacterial properties. In contrast, collagen-based nanoparticles (NPs) as drug delivery systems exhibit both biocompatibility biodegradability, presenting a promising avenue for accelerating healing processes. Aims Study: This review aims provide comprehensive overview the mechanisms involved in healing, description attributes ideal dressings, understanding efficacy collagen, exploring NPs-mediated therapy, detailing synthesis fabrication techniques NPs, delineating applications various NPs infused on healing. Methodology: synthesizes relevant literature from reputable databases such Scopus, Science Direct, Google Scholar, PubMed. Results: A diverse array including nanopolymers, metal nanoemulsions, nanoliposomes, nanofibers, demonstrate pronounced promoting closure tissue regeneration. The incorporation has not only become an agent therapeutics but also actively contributes cascade. Conclusion: conclusion, brief, use presents compelling strategy expediting Keywords: nanoparticles, techniques, collagen

Язык: Английский

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Roles of retinoic acid-related orphan receptor α in high glucose-induced cardiac fibroblasts proliferation

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Diabetic cardiomyopathy, characterized by myocardial fibrosis, is a common complication of diabetes. Retinoic acid-related orphan receptor α (RORα) participates in various pathological and physiological cardiovascular processes. The current research aims to elucidate the roles mechanisms RORα high glucose induced cardiac fibroblasts proliferation. Primary neonatal were isolated from Sprague-Dawley rats, pre-administrated with antagonist SR3335 (20 µM) or agonist SR1078 (10 followed stimulation normal (5.5 mM) (33.3 respectively. Lactate Dehydrogenase (LDH) release into culture medium, cellular adenosine-triphosphate (ATP), cell number detected. Expressions Collagen I, III, proliferating nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), receptor-interacting protein kinase 1 (RIPK1) 3 (RIPK3) evaluated. extent oxidative stress was also assessed. Our study found that elevated LDH release, reduced ATP production, increased cells numbers, expression PCNA, α-SMA, RIPK1 RIPK3, decreased mitochondrial membrane potential, strengthened intensity dihydroethidium (DHE) MitoSOX fluorescence. Above effects all further exacerbated but significantly reversed SR1078. In conclusion, promoted injury proliferation, enhanced collagen synthesis, facilitated necroptosis stimulation, whereas showed opposing effects. proposed as novel target against glucose-induced which beneficial clarify ideal therapeutic implication for diabetic cardiomyopathy.

Язык: Английский

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CSE/H2S Signaling Pathways in Enhancing Muscle Function and Insulin Sensitivity During Exercise

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1741 - 1741

Опубликована: Фев. 18, 2025

Exercise plays a crucial role in maintaining metabolic health, enhancing muscle function, and improving insulin sensitivity, thereby preventing diseases such as type 2 diabetes. Emerging evidence highlights the significance of cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) signaling pathway pivotal regulator molecular physiological adaptations induced by exercise. This review comprehensively examines biosynthesis metabolism H2S, its distribution different tissues, mechanisms which CSE/H2S influences contraction, repair, protein synthesis. Additionally, it explores how modulates pathways, glucose uptake, lipid metabolism, sensitivity. The potential H2S donors exercise supplements is also discussed, highlighting their ability to improve performance health. Current research advancements, including application multi-omics approaches, are reviewed provide deeper understanding complex networks involved. Furthermore, challenges future directions addressed, emphasizing need for further mechanistic studies clinical applications. underscores therapeutic targeting optimize benefits

Язык: Английский

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Distinct Types of Regulated Cell Death in Melanoma

Cells, Год журнала: 2025, Номер 14(11), С. 823 - 823

Опубликована: Июнь 1, 2025

Resistance to cell death is one of the core hallmarks cancer, with regulatory abnormalities particularly pronounced in malignant progression and therapeutic resistance melanoma. This review aims systematically summarize roles mechanisms regulated (RCD) Currently, distinct types RCD, including apoptosis, autophagy, pyroptosis, immunogenic death, necroptosis, ferroptosis, have all been found be involved Autophagy promotes survival melanoma cells under stress conditions through metabolic adaptation, yet its excessive activation can trigger death. Immunogenic has capacity elicit adaptive immune responses immunocompetent syngeneic hosts. Necroptosis, governed by receptor-interacting protein kinase 1 (RIPK1)/RIPK3 mixed lineage domain-like (MLKL) signaling axis, synergize immunotherapy enhance anti-melanoma when activated. Pyroptosis, mediated Gasdermin proteins, induces release inflammatory factors that reshape tumor microenvironment efficacy checkpoint inhibitors. Ferroptosis, characterized lipid peroxidation, overcome targeting solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis. Therapeutic strategies RCD pathways demonstrated breakthrough potential. Several agents developed target order suppress

Язык: Английский

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Suppression of cGAS/STING pathway-triggered necroptosis in the hippocampus relates H2S to attenuate cognitive dysfunction of Parkinson's disease

Experimental Neurology, Год журнала: 2024, Номер 385, С. 115093 - 115093

Опубликована: Дек. 19, 2024

Язык: Английский

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