Radiation-induced Skin Damage Research Articles

Arginine-solubilized lipoic acid-induced β-sheets of silk fibroin-strengthened hydrogel for postoperative rehabilitation of breast cancer

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.

The mechanistic insights and therapeutic implications of sheepskin collagen peptide as a novel anti-photoaging agent

This study explores the protective effects of sheepskin collagen peptide (SSCP) against ultraviolet (UV) radiation-induced skin damage. Molecular docking revealed that SSCP bind to matrix metalloproteinase 1 (MMP-1), forming hydrogen bonds and salt bridges, particularly through interactions with key residues Glu219, Tyr237, Ser239, and Tyr240, thereby potentially inhibiting MMP-1's catalytic activity. In UVA-irradiated human skin fibroblasts, SSCP improved cell viability and migration, reduced matrix metalloproteinases overexpression, and decreased levels of reactive oxygen species and malondialdehyde. Additionally, SSCP suppressed mitogen-activated protein kinase pathway activation, indicated by reduced phosphorylation of JNK and p38, highlighting its role in mitigating oxidative stress and aiding cellular recovery post-UVA exposure. These findings underscore the potential of SSCP as an effective ingredient in anti-photoaging cosmetics and functional foods, offering a comprehensive strategy for preserving skin health and combating UV-induced aging.

Protective Effect of Red Light-Emitting Diode against UV-B Radiation-Induced Skin Damage in SKH:HR-2 Hairless Mice.

In this in vivo study on hairless mice, we examined the effects of light-emitting diode (LED) treatment applied prior to ultraviolet B (UVB) irradiation. We found that pre-treating with LED improved skin morphological and histopathological conditions compared to those only exposed to UVB irradiation. In our study, histological evaluation of collagen and elastic fibers after LED treatment prior to UVB irradiation showed that this pretreatment significantly enhanced the quality of fibers, which were otherwise poor in density and irregularly arranged due to UV exposure alone. This suggests that LED treatment promotes collagen and elastin production, leading to improved skin properties. Additionally, we observed an increase in Claudin-1 expression and a reduction in nuclear factor-erythroid 2-related factor 2 (Nrf-2) and heme-oxygenase 1 (HO-1) expression within the LED-treated skin tissues, suggesting that LED therapy may modulate key skin barrier proteins and oxidative stress markers. These results demonstrate that pretreatment with LED light can enhance the skin's resistance to UVB-induced damage by modulating gene regulation associated with skin protection. Further investigations are needed to explore the broader biological effects of LED therapy on other tissues such as blood vessels. This study underscores the potential of LED therapy as a non-invasive approach to enhance skin repair and counteract the effects of photoaging caused by UV exposure.

Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Naringenin, a flavanone constituent from Sea buckthorn pulp extract, prevents ultraviolet (UV)-B radiation-induced skin damage via alleviation of impaired mitochondrial dynamics mediated inflammation in human dermal fibroblasts and Balb/c mice models

Ultraviolet-B (UV-B) irradiation has been reported to cause oxidative stress and inflammation-mediated skin photo-damage. Furthermore, mitochondrial dynamics have been implicated to play a critical role in these processes. For the first time, we describe in this study how UVB-induced aberrant mitochondrial dynamics and inflammation interact in primary human dermal fibroblasts (HDFs). Our findings demonstrated that UV-B irradiation induced -impairment in mitochondrial dynamics by increasing mitochondrial fragmentation in HDFs. Imbalanced mitochondrial dynamics lead to the activation of NFкB and pro-inflammatory cytokines. The current study further aimed to investigate the protective effect of Naringenin (a naturally occurring flavonoid isolated from Sea buckthorn fruit pulp) against UV-B-induced mitochondrial fragmentation and inflammation in HDFs and Balb/c mice. Although Naringenin has been shown to have anti-inflammatory and antioxidant potential, its effects and mechanisms of action on UVB-induced inflammation remained unclear. We observed that Naringenin restored the UV-B-induced imbalance in mitochondrial fission and fusion in HDFs. It also inhibited the phosphorylation of NFкB and reduced the generation of pro-inflammatory cytokines. Naringenin also alleviated UV-B-induced oxidative stress by scavenging the reactive oxygen species and up-regulating the cellular antioxidant enzymes (Catalase and Nrf2). Topical application of Naringenin to the dorsal skin of Balb/c mice exposed to UV-B radiation prevented mitochondrial fragmentation and progression of inflammatory responses. Naringenin treatment prevented neutrophil infiltration and epidermal thickening in mice's skin. These findings provide an understanding for further research into impaired mitochondrial dynamics as a therapeutic target for UV-B-induced inflammation. Our findings imply that Naringenin could be developed as a therapeutic remedy against UVB-induced inflammation.

Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anticellular Senescence.

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.

Evolution of radiation-induced dermatitis treatment.

Radiation-induced skin damage (RID) is the most prevalent, significant side effect of radiotherapy (RT). Nearly 95% of patients experience moderate to severe skin reactions after receiving radiation therapy. However, criteria for acute radiation dermatitis (ARD) treatment remain unavailable. Topical agents with anti-inflammatory properties may protect the skin and facilitate tissue regeneration in patients with RID. Many of these topical agents function through nuclear factor kappa B pathway regulation. They either reduce the levels of inflammatory factors or elicit anti-inflammatory properties of their own, thus preventing oxidative stress and inflammatory responses and thus enabling RID prevention and management. Herein, we explore the 25 topical agents investigated for RID prevention and management thus far and evaluate their mechanisms of action. These agents include 11 natural agents, 3 miscellaneous agents, 9 topical nonsteroidal agents, and 2 topical corticosteroids.

СРАВНИТЕЛЬНАЯ ОЦЕНКА ВЛИЯНИЯ ЛОКАЛЬНОГО ПРОТОННОГО ИЗЛУЧЕНИЯ В ДОЗЕ 30 ГР НА МЫШЕЙ ЛИНИЙ BALB/с И С57BL/6

Purpose: To evaluate the effect of local proton irradiation at a dose of 30 Gy on Balb/c and C57BL/6 mice in terms of the degree and dynamics of radiation-induced skin damage formation, changes in body weight and peripheral blood elements count. Material and methods: Experiments were performed on non-depilated male mice aged 7‒8 weeks from two strains: Balb/c and C57BL/6 (n=15). Local irradiation of the skin was carried out on the dorsal side of the animals using a scanning proton beam at an extended Bragg peak in the proton therapy complex «Prometheus» of the LPI Physico-technical Centre (Protvino) at a dose of 30 Gy with a proton energy of 87.8 MeV. During the irradiation session, animals were subjected to intraperitoneal anesthesia using a combination of Zoletil 100 (Virbac, France) and Xyla (Interchemie, Netherlands) in a previously determined ratio 1:3 (20‒40 mg/kg). Photographic documentation of radiation-induced skin damage was performed weekly for 70 days. Animals were examined daily for clinical manifestations of radiation-induced skin damage formation according to the RTOG international scale for 21 days following irradiation. The body weight dynamics of mice were evaluated one day before irradiation and then weekly for 70 days. Blood samples were collected from the tail vein by cutting the tip of the tail and analyzed using a DH36 Vet hematology analyzer (Dymind, China) one day before irradiation, one day and three days after irradiation, and weekly thereafter for 70 days. Experimental data were presented as mean ± standard deviation (M ± SD). Results: In this study, the impact of a single local exposure to proton radiation at a dose of 30 Gy on the degree and dynamics of radiation-induced skin damage formation was evaluated. It was demonstrated that Balb/c mice exhibited a higher frequency and degree of radiation-induced skin damage formation compared to the C57BL/6 mice. Analysis of body weight in mice after radiation exposure revealed no significant decrease in either mouse strain. A comparative analysis of the number of platelets, erythrocytes and hemoglobin concentration in both mouse strains did not reveal any changes, while a tendency towards a decrease in the number of leukocytes, lymphocytes, and granulocytes was observed in the irradiated Balb/c mice group compared to the control group. Conversely, in irradiated C57BL/6 mice, the number of lymphocytes was higher compared to control animals. Conclusion: In this study, Balb/c mice exhibited higher radiosensitivity compared to C57BL mice in response to a single local proton irradiation at a dose of 30 Gy.

High-Resolution Ultrasound Imaging for Non-Invasive Characterization of Acute Wound Healing in Radiation Injury on Guinea Pig Skin Tissue

Purpose: High-resolution ultrasound imaging is a non-invasive and objective appraisal. Ultrasound imaging accomplishes the target assessment and follow-up of radiation-induced skin injury.
 The study aimed to investigate the complete anatomical and structural alternations of acute wound healing in skin tissue radiation injury after cell therapy with high-frequency ultrasound imaging techniques.
 Materials and Methods: Female guinea pigs (250 g) were divided into 3 groups: (a) controls, consisting of non-treated guinea pigs; (b) radiation-treated; (c) radiation-treated receiving adipose-derived mesenchymal stem cells. Acute radiation-induced skin injury was induced by a single fraction of X-ray irradiation of 60Gy to a 3.0×3.0-cm area with a 1.3-cm bolus on 100-cm SSD in the abdominal skin tissue. Ultrasonic imaging of the depth and quality of healing in the skin tissue was performed by processing ultrasound images at 40-MHz and 75-MHz frequencies.
 Results: Skin thickness indicated a significant difference between the treatment and control groups on Day 10 after 60 Gy irradiation (P<0.05). The highest skin thickness was observed in the irradiated group, and the lowest skin thickness was found in the stem cell treatment group.
 Conclusion: Evaluation of skin thickness, wound depth, and scar formation is important for the proper assessment and management of wound healing in stem cell therapy of radiation-induced skin damage. High-resolution ultrasound at 40- and 75-MHz frequencies is a major non-invasive method providing unprecedented insight into determining the characterization of the skin, particularly in the context of wound healing.

Mitigation of Nitrogen Mustard-Induced Skin Injury by the β-Blocker Carvedilol and Its Enantiomers.

The chemical warfare agent sulfur mustard and its structural analog nitrogen mustard (NM) cause severe vesicating skin injuries. The pathologic mechanisms for the skin injury following mustard exposure are poorly understood; therefore, no effective countermeasure is available. Previous reports demonstrated the protective activity of carvedilol, a US Food and Drug Administration (FDA)-approved β-blocker, against UV radiation-induced skin damage. Thus, the current study evaluated the effects of carvedilol on NM-induced skin injuries in vitro and in vivo. In the murine epidermal cell line JB6 Cl 41-5a, β-blockers with different receptor subtype selectivity were examined. Carvedilol and both of its enantiomers, R- and S-carvedilol, were the only tested ligands statistically reducing NM-induced cytotoxicity. Carvedilol also reduced NM-induced apoptosis and p53 expression. In SKH-1 mice, NM increased epidermal thickness, damaged skin architecture, and induced nuclear factor κB (NF-κB)-related proinflammatory genes as assessed by RT2 Profiler PCR (polymerase chain reaction) Arrays. To model chemical warfare scenario, 30 minutes after exposure to NM, 10 μM carvedilol was applied topically. Twenty-four hours after NM exposure, carvedilol attenuated NM-induced epidermal thickening, Ki-67 expression, a marker of cellular proliferation, and multiple proinflammatory genes. Supporting the in vitro data, the non-β-blocking R-enantiomer of carvedilol had similar effects as racemic carvedilol, and there was no difference between carvedilol and R-carvedilol in the PCR array data, suggesting that the skin protective effects are independent of the β-adrenergic receptors. These data suggest that the β-blocker carvedilol and its enantiomers can be repurposed as countermeasures against mustard-induced skin injuries. SIGNIFICANCE STATEMENT: The chemical warfare agent sulfur mustard and its structural analog nitrogen mustard cause severe vesicating skin injuries for which no effective countermeasure is available. This study evaluated the effects of US Food and Drug Administration (FDA)-approved β-blocker carvedilol on nitrogen mustard-induced skin injuries to repurpose this cardiovascular drug as a medical countermeasure.

Connexin26 Modulates Radiation-Induced Skin Damage by Regulating Chemokine CCL27 through MAPK Signaling.

Connexin26 (Cx26) plays an important role in ionizing radiation-induced damage, and CC chemokine ligand 27 (CCL27) regulates the skin immune response. However, the relationship between Cx26 and CCL27 in radiation-induced skin damage is unclear. After X-ray irradiation, clonogenic survival and micronucleus formation were assessed in immortalized human keratinocytes (HaCaT). Proteins in the mitogen activated protein kinase (MAPK) signaling pathway and CCL27-related proteins were detected by immunoblotting. HaCaTCx26-/- cells were constructed to verify the effects of Cx26 on CCL27 secretion. A mouse model was established to examine the expression of CCL27 and skin inflammation in vivo. The degree of skin injury induced by 6 MV of X rays was closely related to CCL27. The phosphorylation of ERK, p38 and NF-κB was significantly increased in irradiated cells. The secretion of CCL27 was significantly decreased in HaCaT wild-type cells relative to HaCaTCx26-/- cells. Whereas cell survival fractions decreased, and the micronuclei formation rate increased as a function of increasing X-ray dose in HaCaT cells, the opposite trend occurred in HaCaTCx26-/- cells. Our findings show that Cx26 likely plays a role in the activation of the MAPK and NF-κB/COX-2 signaling pathways and regulates the secretion of CCL27 in keratinocytes after X-ray radiation-induced skin damage.

Keratin 17 Impacts Global Gene Expression and Controls G2/M Cell Cycle Transition in Ionizing Radiation–Induced Skin Damage

Keratin 17 (K17) is a cytoskeletal protein that is part of the intermediate filaments in epidermal keratinocytes. In K17-/- mice, ionizing radiation induced more severe hair follicle damage, whereas the epidermal inflammatory response was attenuated compared with that in wild-type mice. Both p53 and K17 have a major impact on global gene expression because over 70% of the differentially expressed genes in the skin of wild-type mice showed no expression change in p53-/- or K17-/- skin after ionizing radiation. K17 does not interfere with the dynamics of p53 activation; rather, global p53 binding in the genome is altered in K17-/- mice. The absence of K17 leads to aberrant cell cycle progression and mitotic catastrophe in epidermal keratinocytes, which is due to nuclear retention, thus reducing the degradation of B-Myb, a key regulator of the G2/M cell cycle transition. These results expand our understanding of the role of K17 in regulating global gene expression and ionizing radiation-induced skin damage.

FLASH Effects Induced by Orthovoltage X-Rays

This work describes the first implementation and in vivo study of ultrahigh-dose-rate radiation (>37 Gy/s; FLASH) effects induced by kilovoltage (kV) x-ray from a rotating-anode x-ray source. A high-capacity rotating-anode x-ray tube with an 80-kW generator was implemented for preclinical FLASH radiation research. A custom 3-dimensionally printed immobilization and positioning tool was developed for reproducible irradiation of a mouse hind limb. Calibrated Gafchromic (EBT3) film and thermoluminescent dosimeters (LiF:Mg,Ti) were used for in-phantom and in vivo dosimetry. Healthy FVB/N and FVBN/C57BL/6 outbred mice were irradiated on 1 hind leg to doses up to 43 Gy at FLASH (87 Gy/s) and conventional (CONV; <0.05 Gy/s) dose rates. The radiation doses were delivered using a single pulse with the widths up to 500 ms and 15 minutes at FLASH and CONV dose rates. Histologic assessment of radiation-induced skin damage was performed at 8 weeks posttreatment. Tumor growth suppression was assessed using a B16F10 flank tumor model in C57BL6J mice irradiated to 35 Gy at both FLASH and CONV dose rates. FLASH-irradiated mice experienced milder radiation-induced skin injuries than CONV-irradiated mice, visible by 4 weeks posttreatment. At 8 weeks posttreatment, normal tissue injury was significantly reduced in FLASH-irradiated animals compared with CONV-irradiated animals for histologic endpoints including inflammation, ulceration, hyperplasia, and fibrosis. No difference in tumor growth response was observed between FLASH and CONV irradiations at 35 Gy. The normal tissue sparing effects of FLASH irradiations were observed only for high-severity endpoint of ulceration at 43 Gy, which suggests the dependency of biologic endpoints to FLASH radiation dose. Rotating-anode x-ray sources can achieve FLASH dose rates in a single pulse with dosimetric properties suitable for small-animal experiments. We observed FLASH normal tissue sparing of radiation toxicities in mouse skin irradiated at 35 Gy with no sacrifice to tumor growth suppression. This study highlights an accessible new modality for laboratory study of the FLASH effect.

Natural Sun-Screening Compounds and DNA-Repair Enzymes: Photoprotection and Photoaging

Ultraviolet radiation (UVR) has been scientifically proven to cause skin disorders such as sunburn, skin cancer and the symptoms of chronic exposure. Natural sun screening compounds have recently gained tremendous attention from the cosmetic and cosmeceutical sectors for treating skin disorders such as hyperpigmentation and aging. A wide range of natural UV-absorbing compounds have been used to replace or reduce the number of synthetic sunscreen molecules. One of the primary causes of photoaging is DNA damage, mainly caused by UVR. Photoprotection provided by traditional sunscreens is purely preventative and has no efficacy after DNA damage has been initiated. As a result, the quest for DNA-repair mechanisms that block, reverse, or postpone pathologic processes in UV-exposed skin has stimulated anti-photoaging research and methods to increase the effectiveness of traditional sunscreens. This review summarizes many natural compounds from microalgae, lichens, and plants that have demonstrated potential photoprotection effects against UV radiation-induced skin damage. Furthermore, it offers an overview of current breakthroughs in DNA-repair enzymes utilized in sunscreens and their influence on photoaging.

Hemin protects UVB-induced skin damage through inhibiting keratinocytes apoptosis and reducing neutrophil infiltration.

Ultraviolet-B (UVB) exposure on the skin triggers apoptosis, oxidative stress and acute inflammatory responses, which eventually increases the risk of various skin disorders. Hemin, an iron-binding porphyrin, has been clinically used for porphyria treatment. However, whether hemin contributes to the skin protection against UVB injury remains to be elucidated. Here, we found that hemin treatment (10 and 20mg/kg) by intraperitoneal administration could dramatically relieve UVB irradiation-induced skin damage featured by erythema, edema, epidermal hyperplasia and collagen loss in C57BL/6J mice. Importantly, hemin treatment attenuated UVB irradiation-triggered cell apoptosis in skin epidermis. Consistently, hemin (10, 20μM) treatment decreased Caspase-3 activation and protected against UVB-induced apoptosis in HaCaT cells. Besides, hemin treatment reduced the infiltration of neutrophils in skin under UVB irradiation, thus restrained neutrophil extracellular traps (NET) formation and myeloperoxidase (MPO) release. We further revealed that hemin inhibited the expression of inflammation associated cytokines and chemokines in UVB-induced HaCaT cells and blocked the chemotaxis of dHL-60 cells to preconditioned media from HaCaT culture upon UVB irradiation. Furthermore, hemin inhibited the excessive maturation and mobilization of bone marrow neutrophils and rectified the proportion of abnormally elevated neutrophils in the blood under UVB irradiation. In conclusion, our study showed that hemin treatment protects against UVB-induced skin damage through inhibiting keratinocytes apoptosis, and suppressing neutrophils infiltration in the skin via externally restraining the keratinocyte attraction and internally regulating bone marrow neutrophil maturation and mobilization, suggesting that hemin is an effective drug candidate for the therapy of UVB damage.

Immunohistochemical and histochemical analysis of the rat skin after local electron irradiation.

Skin cancer is the most frequently diagnosed type of cancer among all malignant neoplasms. The decrease in mitotic activity and the death of intact keratinocytes arise due to the constantly renewing epithelium being highly sensitive to ionizing radiation. The aim of the study is immunohistochemical evaluation of the proliferative-apoptotic balance of keratinocytes, the fibrous component of the skin, and the expression of pro-inflammatory and anti-inflammatory cytokines after single or fractional local electron irradiation. Wistar rats (n = 80) were taken from the ITM&B Vivarium (Sechenov University) and divided into groups: I-control, which were injected with saline; and experimental groups, local electron irradiation at doses: II-8 Gy (single), III-40 Gy (single), IV-summary dose 78 Gy (fractional; 13 Gy per day for 6 days). We performed histological analysis, histochemical analysis using Masson, safranine, and picrosirius red staining, immunohistochemical (Ki-67, caspase-3, p53, types I and III collagens, IL-1, IL-6, IL-4, and IL-10) and morphometric analysis of skin fragments of the outer surface of the thigh, irradiated in accordance with the design of the experiment. The early and delayed effects of local electron irradiation at different doses were studied. After local electron irradiation, dose-dependent morphological changes in the skin of the experimental groups were observed: violation of the histoarchitectonics of the skin confirmed by morphological and morphometric analysis, the proliferation of connective tissue according to the results of histochemical and immunohistochemical studies with signs of the radiation-induced skin fibrosis development, an increase in the levels of pro- and anti-inflammatory cytokines. We observed the most pronounced signs of radiation-induced skin damage in the group of fractional irradiation after 3 months. 8 Gy and 40 Gy single local electron irradiation leads to a shift in the proliferative-apoptotic balance of keratinocytes toward their apoptosis, which activity is directly correlated with the dose of ionizing radiation, and 78 Gy in fractions leads to partial desquamation of the epithelium and inflammatory infiltration. In addition, after 3 months a significant increase in the expression of type I and III collagen fibers and the development of radiation-induced skin fibrosis takes place against the background of 78 Gy fractional local electron irradiation.

Ginseng glycoprotein and ginsenoside facilitate anti UV damage effects in diabetic rats.

Diabetes mellitus combined with ultraviolet (UV) radiation damage not only brings great mental stress to patients, but also seriously impairs their quality of life. A UV-irradiated diabetic rat trauma skin model was established by us to investigate the effects and possible mechanisms of ginsenoside and glycoprotein on skin trauma repair in UV-irradiated diabetic rats. In the study, ginsenosides and ginseng glycoproteins were extracted from different parts of ginseng roots. It found that it's easier to prepare saponins in ginseng bark and proteins in ginseng core in large quantities. Since glycoprotein-like metabolites are relatively novel ginseng extracts, specifically characterized its structures. It was verified that the ginseng glycoproteins are not toxic to HaCaT cells and can significantly increase the survival of HaCaT cells after UV damage at the in vitro cellular level. Experiments in vivo were conducted to evaluate the therapeutic effects of ginsenoside and ginseng glycoprotein in a rat model of diabetes mellitus combined with UV irradiation injury. Histopathological changes on rat skin after treatment with ginsenoside and ginseng glycoprotein were evaluated by hematoxylin and eosin (H&E) staining and aldehyde fuchsine staining. The expression levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), matrix metalloproteinases (MMPs), hydroxyproline (HYP), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured. The results indicate that both ginsenoside and ginseng glycoprotein could improve skin damage and ulcers caused by diabetes combined with UV irradiation and could alleviate a range of skin damage caused by the combination of diabetes and UV irradiation, including peroxidation and collagen fiber loss. Ginsenoside and ginseng glycoproteins can be considered as natural product candidates for the development of new drugs to treat diabetes combined with UV irradiation-induced skin damage.

Application and clinical efficacy of Sufu medical chitosan hydrogel dressing in radiation skin damage caused by radiotherapy for cervical cancer.

To investigate the benefits of Sufu medical chitosan hydrogel dressing(Sufu) in the prevention and control of radiation skin damage during radiotherapy for cervical cancer as a combined modality. Ninety-seven cervical cancer patients who underwent radiotherapy at the Cancer Hospital of China Medical University between May 2017 and November 2018 were recruited according to given inclusion and exclusion criteria. The patients were assigned to a control group (n=48, washing the perineal area with normal saline) and an observation group (n=49, application of Sufu onto the site of radiotherapy in addition to washing the perineal area with normal saline). The treatment regimens for the two groups continued until the end of radiotherapy. A comparison of the RTOG (Radiation Therapy Oncology Group) grading of acute radiation-induced skin reactions (ARISRs), pain intensity (measured by the verbal rating scale (VRS)) and post-treatment wound healing was drawn between the two groups. In the observation group, 81.6% (40/49) of the patients had radiation dermatitis, which was significantly lower than the incidence rate (95.8%, 46/48) in the control group (P <0.05). The observation group was at higher risk of radiation dermatitis when given a high radiation dose, while the control group was more likely to have radiation dermatitis when administered with a moderate radiation dose (P <0.05). The median time of occurrence of pain and the median time of onset of skin reactions were significantly later in the observation group as compared with the control group (P <0.05, respectively). In the observation group, the pain relief rate was 92.50% at Day-3, and the wound healing rate was 95.0% at Day-7, significantly higher than in the control group (73.9% and 80.4%) (P <0.05, respectively). During radiotherapy for cervical cancer, Sufu can effectively prevent and control radiation-induced skin and mucous membrane damage, delay the onset of radiation dermatitis and substantially reduce the incidence rate, relieve radiation dermatitis and pain and promote wound healing.

Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging

Long-term sun exposure is the commonest cause of photoaging, where mutual interplay between autophagy, oxidative stress, and apoptosis is incriminated. In combating photoaging, pharmacological approaches targeted to modulate autophagy are currently gaining more ground. This study aimed to examine repurposing metformin use in such context with or without the antioxidant coenzyme Q10 (coQ10) in ultraviolet A (UVA) irradiation-induced skin damage. The study was conducted on 70 female CD1 mice that were randomly assigned into seven groups (10/group): normal control, vehicle-treated-UVA-exposed mice, three metformin UVA-exposed groups (Topical 1 and 10%, and oral 300 mg/kg), topical coQ10 (1%)-treated mice, and combined oral metformin with topical coQ10-treated UVA-exposed mice. After UVA-exposure for 10 weeks (3 times/week), macroscopic signs of photoaging were evaluated. Mice were then euthanized, and the skin was harvested for biochemical estimation of markers for oxidative stress, inflammation, matrix breakdown, and lysosomal function. Histopathological signs of photoaging were also evaluated with immunohistochemical detection of associated changes in autophagic and apoptotic markers. Metformin, mainly by topical application, improved clinical and histologic signs of photoaging. This was associated with suppression of the elevated oxidative stress, IL-6, matrix metalloproteinase 1, and caspase, with induction of cathepsin D and subsequent change in anti-LC3 and P62 staining in skin tissue. In addition to metformin antioxidant, anti-inflammatory, and antiapoptotic activities, its anti-photoaging effect is mainly attributed to enhancing autophagic flux by inducing cathepsin D. Its protective effect is boosted by coQ10, which supports their potential use in photoaging.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.