Multifunctional carbomer based ferulic acid hydrogel promotes wound healing in radiation-induced skin injury by inactivating NLRP3 inflammasome.

BACKGROUND: Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury. METHODS: We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis. RESULTS: Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1ß and IL-1ß in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion. CONCLUSIONS: These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients.

Low-dose radiation-induced SUMOylation of NICD1 negatively regulates osteogenic differentiation in BMSCs.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFß thereby promoting transactivation of GPX4.

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor ß (CBFß) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

Improvement of skin wound healing by giant salamander skin mucus gel wrapped with bone marrow mesenchymal stem cells via affecting integrin family molecules.

BACKGROUND: Traditional bandages, gauze, and cotton balls are increasingly insufficient for addressing complex war injuries characterized by severe bleeding and diverse wound conditions. The giant salamander, a species of high medical value, secretes a unique mucus when stimulated, which has potential applications in wound care. MATERIALS: Giant salamander skin mucus gel dressing wrapped with bone marrow mesenchymal stem cells (BMSCs-GSSM-gel) was prepared and validated. Skin wound injury of rabbit and mouse models were established. Hematoxylin and Eosin, Masson's trichrome, and Sirius red staining were performed. The platelet aggregation rate and coagulation items were measured. Transcriptome sequencing was performed to find potential differential expression genes. RESULTS: Preparation and characterization of BMSCs-GSSM-gel were performed, and BMSCs-GSSM-gel particles with a diameter of about 200 nm were obtained. BMSCs-GSSM-gel accelerated wound healing in both rabbit and mouse models. BMSCs-GSSM-gel significantly promoted hemostasis via increasing platelet aggregation rate and fibrinogen, but decreasing activated partial thromboplastin time, thrombin time, and prothrombin time. BMSCs-GSSM-gel treatment significantly impacted several genes associated with cell adhesion, inflammatory response, collagen-containing extracellular matrix, and the positive regulation of cell migration based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Integrin Subunit Beta 4 (ITGB4), Integrin Subunit Alpha 3 (ITGA3), and Laminin Subunit Beta 3 (LAMB3) might be involved in the wound healing process by BMSCs-GSSM-gel. CONCLUSIONS: We proved the BMSCs-GSSM-gel greatly improved the skin wound healing, and it might play a crucial role in the application fields of skin damage repair.

[Research progress of antibacterial hydrogel in treatment of infected wounds].

Objective: To review the research progress of new antibacterial hydrogels in the treatment of infected wounds in the field of biomedicine, in order to provide new methods and ideas for clinical treatment of infected wounds. Methods: The research literature on antibacterial hydrogels at home and abroad was extensively reviewed in recent years, and the antibacterial hydrogels for the treatment of infected wounds were classified and summarized. Results: Antibacterial hydrogels can be divided into three categories: inherent antibacterial hydrogels, antibacterial agent release hydrogels, and environmental response antibacterial hydrogels. The advantages and disadvantages of antibacterial materials, antibacterial mechanism, antibacterial ability, and biocompatibility were discussed respectively. Inherent antibacterial hydrogels have the characteristics of wide source, low cost, and simple preparation, but their antibacterial ability is relatively weak. New antimicrobial substances are added to antibacterial agent release hydrogels, such as antimicrobial peptides, metal ions, graphene materials, etc., providing a new therapeutic strategy for alternative antibiotic therapy. On the basis of the antibacterial material, environmental promoting factors such as photothermal effect, pH value, and magnetic force are added to the environmental response antibacterial hydrogels, which synergically enhances the antibacterial ability of the hydrogel, improves the precise regulation function and bionic effect of the hydrogel. Conclusion: The selection of a variety of materials, the addition of a variety of antibacterial agents, and the effect of various promoting factors make composite hydrogels show multiple characteristics. The development of antibacterial hydrogels that can effectively address practical clinical applications remains a significant challenge. In the future, expanding the application range of antibacterial hydrogels, constructing drug-loaded hydrogels, and developing intelligent hydrogels are still new areas that need to be explored and studied.

Influence factors associated with health risk behaviors of middle school students in the poverty area of China: An observational study.

We aim to investigate the status and influence factors of health risk behaviors among middle school students and explore the relationship between social support, family care, and the health risk behaviors. The study was conducted in 3 middle schools in the Fan county located in the Puyang city. Independent measures were applied to assess adolescent health risk behaviors, perceive social support, and family care. Multiple regression analysis was used to analyze the main factors that affect adolescent health risk behaviors. The total scores of health risk behaviors were 53.87 ± 9.97, and all kinds of health risk behaviors were very common. The highest score was health-compromising (2.45 ± 0.43), and the lowest score was unprotected sex behaviors (1.07 ± 0.28). Multiple regression analysis showed that sex (P < .001), grade (P < .001), parent relationships (P < .001), father's occupation (P = .035), mother's education level (P = .011), social support (P < .001), affection (P < .001), and growth (P = .003) were the main factors of health risk behaviors, accounting for 25.3%. The health risk behaviors among middle school students in Fan county should attract the attention of education administration, schools, and parent due to the varied influencing factors. Related interventions should be conducted to reduce the severity and frequency of adolescent health risk behaviors and protect the health and growth of adolescents. In order to better analyze the health risk behaviors of middle school students, we will incorporate more influencing factors and carry out further causal analysis in the future.

Improvement of irradiation-induced fibroblast damage by α2-macroglobulin through alleviating mitochondrial dysfunction.

CONTEXT: α2-Macroglobulin (α2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear. OBJECTIVE: We investigated the irradiation protective effect of α2-M. MATERIALS AND METHODS: A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of α2-M (100 µg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining. RESULTS: High purity of α2-M was isolated from Cohn fraction IV. α2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by α2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by α2-M. α2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by α2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression. DISCUSSION AND CONCLUSIONS: α2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. α2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of α2-M on irradiation-induced injury.

Management of a patient with cardiac arrest, intestinal ischemia necrosis, multiple fractures, hemorrhagic shock, renal failure, disseminated intravascular coagulation, and thrombosis after severe abdominal crush injury: A case report.

Abdominal crush injury has been widely reported. However, abdominal crush injury cases involving most of the organ systems have seldom been reported. In the present case report, a 58-year-old man was hit in the abdomen by a 4-ton machine tool. The case described a rare combination of cardiac arrest, intestinal ischemia necrosis, multiple fractures, hemorrhagic shock, renal failure, disseminated intravascular coagulation and thrombosis after severe abdominal crush injury. During the treatment, crush syndrome, anemia, electrolyte disorder, pleural effusion, pulmonary emphysema, compartment syndrome, respiratory failure, pulmonary hemorrhage, injury of the right common peroneal nerve and tibial nerve, septum abscess and malnutrition were also observed. Systemic and symptomatic treatments were performed for >3 months, after which the patient was discharged from hospital without any further risk of fatality. The related treatments were also described in detail in the present case report. This case represented one of the most complicated cases among abdominal crush injuries that have been reported, and the treatment experiences reported here will hopefully provide suitable reference points for similar cases.

Influencing Factors of Dyadic Coping Among Infertile Women: A Path Analysis.

Background: The infertility prevalence of married couples in China is increasing gradually. The dyadic coping level and its influencing factors of infertile women in China are poorly reported. The relationship between dyadic coping and the family cohesion and adaptability in infertile women was investigated. Methods: A total of 482 infertile women in the reproductive clinics of three affiliated hospitals of the Lanzhou University were selected by the convenience sampling method. The self-made general information questionnaire, family adaptability and cohesion evaluation scale, and dyadic coping questionnaire were used in this study. Results: The average age of infertile women was 31.73 ± 4.57 years, the duration of infertility was 28.66 ± 27.99 months, the total score of dyadic coping was 132.66 ± 25.49, the total score of family cohesion and adaptability was 101.48 ± 20.96. A significant positive correlation between dyadic coping and family cohesion and adaptability was observed (r = 0.74, p < 0.01). The multiple linear regression analysis showed that religious belief, number of miscarriages, relationship between family members, family intimacy, and adaptability were the influencing factors of dyadic coping level in the family of infertile women (R 2 = 0.566, p < 0.01). Conclusions: The dyadic coping level of infertile women is in the medium level, which is significantly positively correlated with family intimacy and adaptability. In clinical nursing, nurses try to improve the family relationship of patients to increase the level of dyadic coping of infertile women.

Psychological Resilience as the Mediating Factor Between Stigma and Social Avoidance and Distress of Infertility Patients in China: A Structural Equation Modeling Analysis.

BACKGROUND: Stigma, social avoidance and distress may seriously affect the quality of life of infertility patients. Psychological resilience has been proved to effectively combat psychological stress. This study aimed to explore the mediating role of psychological resilience between stigma and social avoidance and distress (SAD) in females with an unfulfilled wish for a child. METHODS: Stigma Scale, Social Avoidance and Distress Scale (SADS), and Psychological Resilience Scale were used to evaluate 266 females with infertility. Structural equation model was used to test the mediating effect of psychological resilience on the relationship between stigma and SAD. RESULTS: The SADS, stigma scores, and psychological resilience scores of 266 females with infertility were 13.36 ± 5.77, 77.84 ± 16.91, and 58.84 ± 12.24 points, respectively. The stigma scores were positively correlated with SADS, and negatively correlated with psychological resilience scores. The psychological resilience scores were negatively correlated with SADS. Psychological resilience played a partially mediating role between the stigma and SAD of infertility patients, and the mediating effect accounted for 25.5% of the total effect. CONCLUSION: Psychological resilience had a partial mediating effect on the relationship between stigma and SAD, and could reduce the negative effect of stigma on the development of SADS. Therefore, positive psychological interventions improving psychological resilience might help to reduce stigma and improve SAD in infertility patients.