Regulatory T cells in skin regeneration and wound healing

As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.

Therapeutic approach to emotional reactions accompanied with thermal skin injury–from basic to epidemiological research

In this editorial,we discuss the status of a therapeutic approach to emotional reactions accompanying thermal skin injuries.Burns are considered a major health problem,as well as an economic and social problem,with potentially devastating and life-changing consequences.They affect a wide range of patients with different damage mechanisms,varied depths,and localizations of the burns.The most common are thermal burns,with more than 11 million occurrences annually according to the World Health Organization data.Thermal skin injuries are among the most tragic and catastrophic injuries,almost unsurpassed in terms of severity,morbidity,and mortality,as well as functional,aesthetic,social,economic,and psychological consequences.Burn survivors face stress,anxiety,depression,low self-esteem,body deformity,social isolation,unemployment,financial burden,and family problems.The advances in acute burn care have allowed researchers and physicians to pay more attention to other effects of burns,focusing on psychological consequences in particular.Apart from the significant improvements in routine protocols,it seems useful to take care of psychological disturbances that occur simultaneously but may emerge as the most lasting outcome of those injuries.In that sense,various standards and additional approaches may be involved to achieve overall recovery.

Risk Factors of Neonatal Medical Adhesive-Related Skin Injury and Management of High-Risk Nodes

Objective:To analyze the risk factors of neonatal medical adhesive-related skin injury and put forward targeted preventive measures,so as to provide reference for the care and prevention of neonatal medical adhesive-related skin injuries.Methods:Using the convenience sampling method,262 neonates admitted to the neonatal intensive care unit(NICU)of a tertiary general hospital in Wenzhou from April 2021 to May 2022 were selected as the study subjects.The incidence of medical adhesive-related skin injuries in these neonates was retrospectively analyzed.Results:Among the 262 children,43 cases had skin injuries,with an incidence rate of 16.4%.Single factor analysis showed that the occurrence of medical adhesive-related skin injury was related to gestational age,weight,electrocardiogram(ECG)monitoring,venous access,ambient temperature,and mechanical ventilation(P<0.05).Multivariate logistic regression showed that gestational age,ECG monitoring,and ambient temperature were independent risk factors of medical adhesive-related skin injury(OR values were 0.700,0.431,and 6.365,respectively).Conclusion:The high incidence of neonatal medical adhesive-related skin injury may be caused by one or more factors.Clinical measures should be taken,such as selecting the appropriate type of adhesive according to gestational age and using skin-protecting membrane,minimizing ECG monitoring,etc.,to prevent the occurrence of neonatal medical adhesive-related skin injury.

Skin damage due to personal protective equipment among nursing staff in a dedicated coronavirus disease-2019 hospital of tribal India

Background:Nursing staff are at much greater risk of infection(Ebola virus diseases and severe acute respiratory syndrome)due to their exposure to highly infectious bodily fluids and droplet nuclei and the need for personal protective equipment(PPE)to reduce the transmission risk.Aim:The present study was conducted to estimate the prevalence of skin injuries and their types due to PPE usage among nursing staff in tribal India.Materials and Methods:This descriptive cross-sectional study was conducted in the dedicated coronavirus disease-2019(COVID-19)hospital for a period of 4 months among 144 nursing staff wearing Grade 2 and 3 PPE kits.Study subjects were approached through social networking websites and survey questionnaires(Google forms)according to relevant guides,and research literature was used to collect the details regarding baseline,duty,and skin injury characterization.Chi-square test was used to find the association between skin injury and baseline or duty characteristics,and the association was significant at a P<0.05.Results:It was observed that 54.7%of nursing staff were working for 6 or more hours and 16.5%of subjects were wearing the PPE kit for 5 or more hours per day.Skin injury was reported by 86.3%of the subjects after using PPE.Skin injuries among nurses were statistically significant with their current place of stay and daily duty hours(P<0.05).Conclusion:In this study,it was found that 86.3%of subjects had suffered from skin injuries by using PPE while caring for COVID-19 patients during duty hours,so an effective preventive measure should be adopted.

Application of free vein skin flap on the anterior aspect of wrist in the case of finger injury with vessel and skin defect

Objective To introduce an effective reconstruction method for the finger injured with vessel and skin defect. Methods Free skin flap with skin vein was transplanted on the site of tissue defect, connecting by anastomosis the vein with artery or vein of the finger. Results Seven cases were treated with this method,among which 5 cases have sikin defect on the palm aspect of fingers, the rest have skin defect on the dorsal aspect skin of finger. All fingers survived with good shape and function. Conclusion This is a simple and effective method of finger reconstruction for the patients with defect of vessels and skin. 6 refs.

Optimization-based conformal path planning for in situ bioprinting during complex skin defect repair

The global demand for effective skin injury treatments has prompted the exploration of tissue engineering solutions.While three-dimensional(3D)bioprinting has shown promise,challenges persist with respect to achieving timely and compatible solutions to treat diverse skin injuries.In situ bioprinting has emerged as a key new technology,since it reduces risks during the implantation of printed scaffolds and demonstrates superior therapeutic effects.However,maintaining printing fidelity during in situ bioprinting remains a critical challenge,particularly with respect to model layering and path planning.This study proposes a novel optimization-based conformal path planning strategy for in situ bioprinting-based repair of complex skin injuries.This strategy employs constrained optimization to identify optimal waypoints on a point cloud-approximated curved surface,thereby ensuring a high degree of similarity between predesigned planar and surface-mapped 3D paths.Furthermore,this method is applicable for skin wound treatments,since it generates 3D-equidistant zigzag curves along surface tangents and enables multi-layer conformal path planning to facilitate the treatment of volumetric injuries.Furthermore,the proposed algorithm was found to be a feasible and effective treatment in a murine back injury model as well as in other complex models,thereby showcasing its potential to guide in situ bioprinting,enhance bioprinting fidelity,and facilitate improvement of clinical outcomes.

Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

Estrogen is imperative to mammalian reproductivity,metabolism,and aging.However,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain malignancies.In contrast,ERβis more broadly expressed in metabolic tissues and the skin.Thus,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERαactivation.Here,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or genistein.Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in vitro.We further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound healing.Therefore,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

Edaravone Enhances the Viability of Ischemia/reperfusion Flaps

The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion（IR） and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups： control group（n=16）, IR group（n=16）, and edaravone-treated IR group（n=16）. An island flap at left lower abdomen（6.0 cm×3.0 cm in size）, fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone（10 mg/kg）, once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde（MDA） and activity of superoxide dismutase（SOD） were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin（HE） staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling（TUNEL） assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy（TEM）. Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.

Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis,whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer.Herein,we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy.The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin(DOX)formed by consecutive ultrasonication-inducedβ-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion,exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy,as well as simultaneous release of DOX to finally achieve effective anti-cancer effect.A stretchable bioadhesive is fabricated by copolymerization ofα-thioctic acid and N,N-diacryloyl-L-lysine,and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions.The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing.Ultimately,in vivo animal studies substantiate the efficacy of our methodology,wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.

Radiation dermatitis wet healing:a concept analysis

Objective:To explore the concept of radiation dermatitis wet healing through a literature review and provide references for future treatment of patients with radiation skin injury.Methods:Related ar ticles selected from China National Knowledge Infrastructure(CNKI),Wanfang Database,Pub Med,Web of Science,Medline,and EBSCO were analyzed with Rodger’s concept analysis.Results:We identified the application status of wet healing in domestic and foreign literature,defined explicit attributes of the procedure,and clarified concepts related to wet healing of radiation skin injury to provide a reference for the management of radiation dermatitis with wet healing.Conclusions:Treatment of radiation dermatitis with wet healing is a unique procedure.Analyzing this concept can contribute to its development in the future and can offer a theoretical basis for treatment of patients with radiation skin injury.

Tacrolimus may play a role in dermatitis and radiation-induced skin injury through cellular senescence

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects,resulting in radiation-induced skin injury(RSI).Premature cellular senescence,caused by oxidative stress and/or DNA damage from chemical or physical agents,leads to the decrease of cellular proliferation and physiological function.Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury.Atopic dermatitis and RSI have similar inflammatory symptoms.The treatment of tacrolimus(TAC)in atopic dermatitis may be associated with premature cellular senescence.TAC can prevent the onset of cellular senes-cence by inactivating the p38 mitogen-activated protein kinase(p38 MAPK).The activation of p38 MAPK can induce the senescence-associated secretory phenotype(SASP)by enhancing the transcriptional activity of nuclear factor kappa-B(NF-κB),which ultimately leads to premature cellular senescence.FK506 binding protein 51(FKBP51)exhibits resistance to ionizing radiation,but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study.This review discusses the mechanism of cellular senes-cence in RSI and the role of TAC in both dermatitis and RSI.

Prevention and treatment for radiation-induced skin injury during radiotherapy

The skin tissue has the largest area in the human body and functions as both a barrier and a defender.As such,it tends to be the first tissue to be damaged.Advances in medical technology provide prospects as well as side effects,for example,radiation therapy for cancer.With increasing cancer morbidity and radiation widely applied for cancer therapy,radiation-induced skin injury(RSI)has become a serious concern.In recent decades,research efforts have focused on the mechanisms underlying RSI.This review summarizes the mainstream opinions on these mechanisms,including the pathological,molecular biological,and cytobiological alterations.Radiationinduced reactive oxygen species(ROS),cytokines and involved signaling pathways are evaluated.Other relevant aspects include radiation-induced skin fibrosis(RSF)and radiation-related skin cell senescence.Moreover,we review strategies for the prevention and treatment in clinical and pre-clinical studies to support the treatment of RSI during radiotherapy.The prevention strategies include dose control,pre-irradiation instructions,and RSI assessments,while the main treatments include physical therapy,external-use dressings or creams,biological therapy and surgical reconstruction.

RXRα agonist bexarotene attenuates radiation-induced skin injury by relieving oxidative stress

Objective: To investigate the protective effect of bexarotene in radiation-induced skin injury and elucidate underlying mechanism.Methods: Irradiated cellular and animal models were established using an X-ray linear accelerator. Cell viabilityand apoptosis were evaluated by CCK8 and flow cytometry. In vivo protective effect of bexarotene was measuredin irradiated SD rats. The antioxidant capacity of bexarotene was validated by DCF-DA method. The signalingpathways involved in bexarotene-mediated skin repair were enriched by RNA sequencing.Results: Bexarotene could significantly restore the proliferation and inhibit the apoptosis of WS1 cells with radiation damage (P < 0.05). Moreover, bexarotene could effectively shorten the process of skin damage andpromote skin repair in a rat model of radiation-induced skin injury (P < 0.05). Mechanistically, bexaroteneeffectively reduced the expression of RXRα (P < 0.05), thus leading to an early decrease in reactive oxygen species(ROS) after radiation exposure. Furthermore, a transcriptome analysis indicated that bexarotene-mediated recovery of radiation damage involves redox signaling, immune regulation, lipid metabolism and autophagy.Conclusion: Bexarotene is a promising therapeutic agent in the treatment of radiation-induced skin injury.

Effects of combined radiation and thermal burn injury on the survival of skin allograft and immune function in rats

Abstract Objectives To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival and the changes of immune functions of the thymocytes and splenocytes in rats. Methods Wistar rats were irradiated with 3, 4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA Ⅲ degree burn was inflicted to the rats. Twenty four hours after the burn injury, allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before skin grafting, the bone marrow cells (4×10 8) from the same donor were also transplanted. All rats were carefully observed after injury. The rats with single radiation injury of 5 Gy gamma rays, with single burn injury and with combined radiation burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting for immunological assay and pathological study. Results All the allografts in the single burn group were rejected in 10 days. In the combined injury groups, the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were 20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy radiation, the 10 day survival rates of the allografts were 69%, 88% and 100% respectively, and the 30 day survival rates in the three groups were 36%, 42% and 100% separately. The grafted allogenic skin, with normal epithelial cells and good vascularity, healed well with the recipient's skin. Hairs grew well from the allografts 30 days after grafting. Three, 7 and 15 days after allografting, in the single burn group, the proliferative activities of the thymocytes were 90%, 185% and 130% of the preinjury level, and the antibody forming capacities of the splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the combined injury groups, the proliferative activities were 6%, 99% and 91% of the preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury level. Conclusions The survival rate of allograft in rats undergoing combined radiation and thermal burn injury rises with the increase in radiation dosage. The allograft covering single bun injury is severely rejected by immune reaction. The prolongation of the survival of allograft in combined injury group mainly results from radiation that suppresses immune functions.