IL-17 in wound repair: bridging acute and chronic responses.

Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17's involvement in chronic wound inflammation and repair.

The Role of p53 in Regulating Chronic Inflammation and PANoptosis in Diabetic Wounds.

Diabetic wounds represent a formidable challenge in the clinical management of diabetes mellitus, markedly diminishing the patient's quality of life. These wounds arise from a multifaceted etiology, with the pathophysiological underpinnings remaining elusive and complex. Diabetes precipitates neuropathies and vasculopathies in the lower extremities, culminating in infections, ulcerations, and extensive tissue damage. The hallmarks of non-healing diabetic wounds include senescence, persistent inflammation, heightened apoptosis, and attenuated cellular proliferation. The TP53 gene, a pivotal tumor suppressor frequently silenced in human malignancies, orchestrates cellular proliferation, senescence, DNA repair, and apoptosis. While p53 is integral in cell cycle regulation, its role in initial tissue repair appears to be deleterious. In typical cutaneous wounds, p53 levels transiently dip, swiftly reverting to baseline. Yet in diabetic wounds, protracted p53 activation impedes healing via two distinct pathways: i) activating the p53-p21-Retinoblastoma (RB) axis, which halts the cell cycle, and ii) upregulating the cGAS-STING and nuclear factor-kappaB (NF-κB) cascades, instigating ferroptosis and pyroptosis. Furthermore, p53 intersects with various metabolic pathways, including glycolysis, gluconeogenesis, oxidative phosphorylation, and autophagy. In diabetic wounds, p53 may drive metabolic reprogramming, thus potentially derailing macrophage polarization. This review synthesizes case studies investigating the therapeutic modulation of p53 in diabetic wounds care. In summation, p53 modulates chronic inflammation and cellular aging within diabetic cutaneous wounds and is implicated in a novel cell death modality, encompassing ferroptosis and pyroptosis, which hinders the reparative process.

SOX family transcription factors as therapeutic targets in wound healing: A comprehensive review.

The SOX family plays a vital role in determining the fate of cells and has garnered attention in the fields of cancer research and regenerative medicine. It also shows promise in the study of wound healing, as it actively participates in the healing processes of various tissues such as skin, fractures, tendons, and the cornea. However, our understanding of the mechanisms behind the SOX family's involvement in wound healing is limited compared to its role in cancer. Gaining insight into its role, distribution, interaction with other factors, and modifications in traumatized tissues could provide valuable new knowledge about wound healing. Based on current research, SOX2, SOX7, and SOX9 are the most promising members of the SOX family for future interventions in wound healing. SOX2 and SOX9 promote the renewal of cells, while SOX7 enhances the microvascular environment. The SOX family holds significant potential for advancing wound healing research. This article provides a comprehensive review of the latest research advancements and therapeutic tools related to the SOX family in wound healing, as well as the potential benefits and challenges of targeting the SOX family for wound treatment.

Neuropeptide substance P: A promising regulator of wound healing in diabetic foot ulcers.

In the past, neuropeptide substance P (SP) was predominantly recognized as a neuroinflammatory factor, while its potent healing activity was overlooked. This paper aims to review the regulatory characteristics of neuropeptide SP in both normal and diabetic wound healing. SP actively in the regulation of wound healing-related cells directly and indirectly, exhibiting robust inflammatory properties, promoting cell proliferation and migration and restoring the activity and paracrine ability of skin cells under diabetic conditions. Furthermore, SP not only regulates healing-related cells but also orchestrates the immune environment, thereby presenting unique and promising application prospects in wound intervention. As new SP-based preparations are being explored, SP-related drugs are poised to become an effective therapeutic intervention for diabetic foot ulcers (DFU).

Asiaticoside Prevents Oxidative Stress and Apoptosis in Endothelial Cells by Activating ROS-dependent p53/Bcl-2/Caspase-3 Signaling Pathway.

BACKGROUND: Asiaticoside (AC) is a triterpenoid saponin found in Centella asiatica (L.) urban extract that has a wide range of pharmacological properties. Our previous study demonstrated that AC could promote angiogenesis in diabetic wounds, but the specific mechanisms remain unknown. OBJECTIVE: This study aimed to examine the effectiveness and mechanism of AC on human umbilical vein endothelial cells (HUVECs) exposed to tert-butyl hydroperoxide (t-BHP) toxicity. METHODS: Senescence was confirmed using senescence-associated betagalactosidase (SA-ß-gal) activity and expression of the cell cycle phase markers p16 and p21. The levels of SOD, NO, MDA, GSH-Px, and ROS were tested. Furthermore, several cell death-related genes and proteins (p53, Bax, Bcl-2 and Caspase-3) were assessed with RT-qPCR and Western blotting. RESULTS: AC significantly reduced SA-ß-gal activity, with both the suppression of cellcycle inhibitors p16 and p21. We also found that the induced oxidative stress and apoptosis caused by t-BHP treatment resulted in the decrease of antioxidant enzymes activities, the surge of ROS and MDA, the up-regulation of p53, Bax and caspase-3, and the decrease of SOD, NO, GSH-Px and Bcl-2. These biochemical changes were all reversed by treatment with varying doses of AC. CONCLUSION: AC alleviates t-BHP-induced oxidative injury and apoptosis in HUVECs through the ROS-dependent p53/Bcl-2/Caspase-3 signaling pathway. It may be a potential antioxidant applied in metabolic disorders and pharmaceutical products.