This review explores the mechanisms of chronic radiation-induced skin injury fibrosis, focusing on the transition from acute radiation damage to a chronic fibrotic state. It reviewed the cellular and molecular responses of the skin to radiation, highlighting the role of myofibroblasts and the significant impact of Transforming Growth Factor-beta (TGF-β) in promoting fibroblast-to-myofibroblast transformation. The review delves into the epigenetic regulation of fibrotic gene expression, the contribution of extracellular matrix proteins to the fibrotic microenvironment, and the regulation of the immune system in the context of fibrosis. Additionally, it discusses the potential of biomaterials and artificial intelligence in medical research to advance the understanding and treatment of radiation-induced skin fibrosis, suggesting future directions involving bioinformatics and personalized therapeutic strategies to enhance patient quality of life.

Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis

Skin wound healing is a complex and tightly regulated process. The frequent occurrence and reoccurrence of acute and chronic wounds cause significant skin damage to patients and impose socioeconomic burdens. Therefore, there is an urgent requirement to promote interdisciplinary development in the fields of material science and medicine to investigate novel mechanisms for wound healing. Cerium oxide nanoparticles (CeO 2 NPs) are a type of nanomaterials that possess distinct properties and have broad application prospects. They are recognized for their capabilities in enhancing wound closure, minimizing scarring, mitigating inflammation, and exerting antibacterial effects, which has led to their prominence in wound care research. In this paper, the distinctive physicochemical properties of CeO 2 NPs and their most recent synthesis approaches are discussed. It further investigates the therapeutic mechanisms of CeO 2 NPs in the process of wound healing. Following that, this review critically examines previous studies focusing on the effects of CeO 2 NPs on wound healing. Finally, it suggests the potential application of cerium oxide as an innovative nanomaterial in diverse fields and discusses its prospects for future advancements. 

pdf/cerium-oxide-nanoparticles-in-wound-care-a-review-of-trff20eg6r.pdf

Cerium oxide nanoparticles in wound care: a review of mechanisms and therapeutic applications

Radiation therapy, a fundamental treatment for tumors, is often accompanied by radiation-induced skin injury (RISI). Excessive production of reactive oxygen species (ROS) and subsequent inflammation are two key factors in RISI development that will cause skin injury and affect radiotherapy. Herein, the co-assembled binary polyphenol natural products inspired the development of a dual-functional cascade microneedle system for prevention and treatment of RISI. Specifically, epigallocatechin gallate (EGCG) and curcumin (CUR) were co-assembled into nanoparticles (CEPG) by intermolecular interactions and then incorporated with catalase (CAT) to achieve a cascade system in the microneedles (this microneedle system was conducive to penetrate into the epidermal keratinocytes where RISI had the greatest impact). When using microneedles, the tip dissolved rapidly and delivered CEPG and CAT into the dermis, where CEPG NPs were able to respond to ROS and decompose into EGCG and CUR. More importantly, EGCG and CAT formed a cascade that converts superoxide anions into water step-by-step, which can reduce cell damage caused by free radicals in the early stages of radiation for prevention; meanwhile, CUR inhibited inflammatory pathways, achieving the treatment of skin inflammation in the post-radiotherapy period. These explorations broaden the strategy for the application of natural products in RISI. 

Co-Assembled Binary Polyphenol Natural Products for the Prevention and Treatment of Radiation-Induced Skin Injury

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair. 

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury

Abstract The reduction of nitric oxide (NO) bioavailability in the endothelium induces endothelial dysfunction, contributing to the development of hypertension. Although Lactobacillus consumption decreases blood pressure, intracellular signaling pathways related to hypertension have not been well elucidated. Thus, this study examined the effect of spray-dried Lactiplantibacillus plantarum K79 (LpK79) on NO production, intracellular signaling pathways, and inflammatory responses related to vascular function and hypertension. NO production was assessed in human umbilical vein endothelial cells (HUVECs) treated with LpK79. Endothelial NO synthase (eNOS) and intracellular signaling molecules were determined using Western blot analysis. LpK79 dose-dependently increased NO production and activated eNOS via the phosphoinositide 3-kinase/Akt signaling pathway HUVECs. Moreover, LpK79 mitigated the activation of crucial factors pivotal for vascular contraction in smooth muscle cells, such as phospholipase Cγ, myosin phosphatase target subunit 1, and Rho-associated kinase 2. When HUVECs were treated with LpL79 in the presence of Escherichia coli lipopolysaccharide (LPS), LpK79 effectively suppressed mRNA and protein expression of pro-inflammatory mediators induced by E. coli LPS. These results suggest that LpK79 provided a beneficial effect on the regulation of vascular endothelial function.

Regulatory effect of spray-dried Lactiplantibacillus
 plantarum K79 on the activation of vasodilatory factors and
 inflammatory responses

Screening efficient strains by cell platform is cost-effective, but to date, no screening experiments have been performed for targeted lactic acid bacteria with hypoxic/reoxygenation (H/R)-treated cardiomyocytes, and their effects on the phosphoinositide 3-kinase (PI3K)/protein kinase b (Akt)/endothelial nitric oxide synthase (eNOS) pathway in myocardial infarction (MI) are unclear. Here we activated 102 strains of lactic acid bacteria and inoculated them into MRS medium for fermentation. The fermentation supernatants of the lactic acid bacteria were incubated with an H/R model of H9C2 cells. We found that Bifidobacterium longum ZL0210 had the greatest potential for inhibiting the apoptosis of H/R-induced H9C2 cells. Furthermore, it significantly increased the expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) in H9C2 cardiomyocytes, as well as the Bcl-2/Bax protein ratio, protecting damaged myocardial cells via an anti-apoptotic pathway. Intragastric administration of B. longum ZL0210 to mice for one week before and after establishment of an MI model drastically attenuated the myocardial cell hypertrophy and fibrosis of the MI mice. Meanwhile, B. longum ZL0210 significantly reduced the secretion of myocardial enzymes, increased the activity of antioxidant enzymes, and inhibited lipid-oxidative malondialdehyde (MDA) levels. Moreover, it upregulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein and the phosphorylation levels of PI3K, Akt, and eNOS, resulting in increased NO contents. In summary, we screened 102 strains of lactic acid bacteria with a cell platform and determined that B. longum ZL0210 was a favorable candidate for protecting the myocardium. We are the first to reveal the protective effects of B. longum ZL0210 for MI via activation of the PI3K/Akt/eNOS pathway through TRAIL.

https://www.jstage.jst.go.jp/article/bmfh/42/1/42_2021-044/_pdf

Screening of the most efficacious lactic acid bacteria strain for myocardial infarction recovery and verification and exploration of its functions and mechanisms

Radiation skin injury is a frequent adverse effect of radiation therapy for malignant tumors. It often leads to problems such as decreased quality of life in patients and interferes with the normal course of radiation therapy. With the rising incidence of tumors and the burgeoning number of patients undergoing radiation therapy, the care of radiation skin injury is of crucial importance in cancer patient treatment. Currently, drugs and biomaterials are widely used in the care of radiation skin injury. However, there is no international consensus on the current protocol for the therapeutic care of radiation skin injury. Many drugs and biomaterials cannot be applied to the appropriate type of radiation dermatitis, resulting in unfavorable results in the therapeutic care of radiation skin injury. The choice of appropriate drugs and biomaterials for the therapeutic care of the different types of radiation skin injury is essential to improving the quality of life of patients. In this article, we first review the main mechanisms of acute and chronic radiation skin injury. Subsequently, we summarize the application of drugs and novel biomaterials in the preventive, acute, and chronic phases of the care of radiation skin injury. Finally, the suggestions and protocols for the application of novel biomaterials in the care of radiation skin injury are discussed, as are the current challenges and future prospects for the development of combined biomaterials and integrated care solutions. This article is protected by copyright. All rights reserved 

Radiation Skin Injury Care in Radiotherapy for Oncology: Mechanisms, Drug Therapy and Novel Biomaterial Application Strategies

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Screening of the most efficacious lactic acid bacteria strain for myocardial infarction recovery and verification and exploration of its functions and mechanisms

Radiation Skin Injury Care in Radiotherapy for Oncology: Mechanisms, Drug Therapy and Novel Biomaterial Application Strategies