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Irradiation-induced skin ulcers can be resultant from nuclear accident or reaction to radiation therapy of tumor and is intractable for healing. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been considered to be the potential therapeutic tools for tissue regeneration. However, the underlying mechanisms are still not well understood. This study aims to investigate the effects of hUC-MSCs on irradiation-induced skin ulcers healing and the related mechanisms. The ulcers were induced by irradiating the skin of adult SD rats. The ulcers of SD rats were treated with vehicle or hUC-MSCs donated from mother giving birth. The ulcer healing was measured by imaging the healing rate and the H&E staining. CD31 and VEGF expression was measured with immunohistochemistry assay. iTRAQ proteomics analysis was used to analyze the signaling pathway. The results showed that hUC-MSCs improved healing of irradiation-induced skin ulcers in vivo using a rat model of skin ulcer. Transplantation of hUC-MSCs promoted keratin generation and keratinocytes proliferation of ulcer areas. Furthermore, the results demonstrated that hUC-MSCs increased expression of CD31 and VEGF in ulcers and promoted neovascularization. iTRAQ proteomics analysis results indicated that PI3K/Akt signaling pathway involved in hUC-MSCs-mediated repairing of irradiation-induced skin ulcer. In conclusion, human umbilical cord mesenchymal stem cells promoted neovascularization and re-epithelization, and improved healing of irradiation-induced skin ulcers. This healing improvement may be conducted through activating the PI3K/Akt signaling pathway, however, which needs to be proven by the further investigations. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation is ubiquitous in the environment, which has been classified as an established human carcinogen. As the largest and outermost organ of the body, direct exposure of skin to sunlight or UV radiation can result in sunburn, inflammation, photo-immunosuppression, photoaging and even skin cancers. To date, there are tactics to protect the skin by preventing UV radiation and reducing the amount of UV radiation to the skin. Nevertheless, deciphering the essential regulatory mechanisms may pave the way for therapeutic interventions against UV-induced skin disorders. Additionally, UV light is considered beneficial for specific skin-related conditions in medical UV therapy. Recent evidence indicates that the biological effects of UV exposure extend beyond the skin and include the treatment of inflammatory diseases, solid tumors and certain abnormal behaviors. This review mainly focuses on the effects of UV on the skin. Moreover, novel findings of the biological effects of UV in other organs and systems are also summarized. Nevertheless, the mechanisms through which UV affects the human organism remain to be fully elucidated to achieve a more comprehensive understanding of its biological effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • MnO 2 /PDA@Cu nanosheets: Cu added to MnO 2 via PDA. • MnO 2 /PDA@Cu-HA microneedle: delivers agents to wounds. • MnO 2 /PDA@Cu-HA: fights bacteria, clears ROS, promotes vascularization. • MnO 2 /PDA@Cu-HA: speeds up wound healing. Effective treatment of infected diabetic wound (IDW) requires delivering therapeutic agents to both wound surface and deep layers, as well as improving the wound microenvironment through antibacterial actions, clearing excessive reactive oxygen species (ROS), and promoting vascular regeneration. Here, we present a novel inorganic nanosheet called MnO 2 /PDA@Cu, consisting of manganese dioxide (MnO 2) with copper (Cu) ions loaded on its surface through in-situ polymerization, using polydopamine (PDA) as an intermediate. We then encapsulated the MnO 2 /PDA@Cu nanosheet into a methacrylated hyaluronic acid (HA) soluble microneedle patch, creating a photodynamic-controllable multifunctional MnO 2 /PDA@Cu-HA microneedle. We used this microneedle to treat IDWs in a rat full-thickness skin defect model. Results demonstrated that the MnO 2 /PDA@Cu-HA microneedle effectively delivered therapeutic agents to both wound surface and deep layers, where PDA's photodynamic therapy swiftly combated bacteria under 808 nm near-infrared irradiation. Simultaneously, MnO 2 acted as a nanoenzyme, mitigating ROS levels and providing oxygen for wound healing. In addition, the photothermal effect of PDA further facilitated the release of Cu, promoting vascularization. The MnO 2 /PDA@Cu-HA microneedle significantly accelerated wound closure, re-epithelialization, and collagen deposition, enhancing IDW healing. In conclusion, our synthesized MnO 2 /PDA@Cu-HA microneedle represents a photodynamic-controllable multifunctional platform for IDW treatment, offering a promising approach for effective wound management. [ABSTRACT FROM AUTHOR]

[Display omitted] • We developed a multifunctional core-shell nanofiber loaded with CTS in the shell layer, Cu and DWJM in the core layer. • Initial released CTS exerts antibacterial activity and sustain released Cu drives cell migration and neovascularization. • DWJM accelerated the deposition of collagen and these three bioactive agents synergistically enhanced DW healing. Infected diabetic wound (DW) healing entails a series of temporally and spatially regulated stages including antibacterial responses, revascularization, and collagen deposition, underscoring the need for the controlled sequential delivery of appropriate compounds when treating these wounds. Here, we designed a multifunctional core–shell CTS@PLCL/DWJM@Cu nanofiber loaded with three bioactive agents, including chitosan (CTS), copper (Cu), and decellularized Wharton's jelly matrix (DWJM). We used this platform to facilitate regulated antibacterial, angiogenic, and collagen deposition activity in the context of DW healing. These CTS@PLCL/DWJM@Cu nanofibers exhibited satisfactory mechanical properties, excellent absorption, acceptable biodegradability, a high level of biocompatibility, elevated adhesive rates, and the ability to sequentially mediate controlled sequential CTS and Cu release. Further in vitro analyses revealed that the initial release of the CTS shell was sufficient to exert antibacterial activity, after which the sustained release of the Cu core promoted cellular migration, neovascularization, and enhanced angiogenesis-related gene expression. In vivo, DWJM further accelerated the deposition of collagen. Together, the sequential antibacterial, angiogenic, and collagen deposition activities synergistically enhanced DW healing. We thus posit that the core–shell CTS@PLCL/DWJM@Cu nanofiber holds great promise for use as a dressing material capable of promoting the appropriate stages of DW healing in a regulated, sequential manner. [ABSTRACT FROM AUTHOR]

B7-H3 is a type I membrane protein that has contradictory co-stimulatory and co-inhibitory effects in adaptive and anti-tumour immunity. B7-H3 is up-regulated in many malignant tumours, including breast cancer. Therefore, we hypothesise that B7-H3, which has an immunosuppressive role, suppresses anti-tumour immunity. The aim of this study was to clarify the role of B7-H3 in the tumor microenvironment in breast cancer, explore the possibility of B7-H3 as a target for clinical immunotherapy, and provide reference for clinical work. We knocked down B7-H3 with siRNA in MCF7 breast cancer cells, which we termed MCF7-B7-H3-KD cells, and the expression of B7-H3 was assessed by flow cytometry. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) knockdown was used as a control (MCF7-Gapdh). MCF7-B7-H3-KD and MCF7-Gapdh cells were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD3+ T cells from healthy donors to assess the effect of B7-H3 loss. PBMCs cultured with MCF7-Gapdh cells showed decreased activation, proliferation, and function of CD8+ T cells, but there was no effect on the proliferation of CD4+ T cells. However, when MCF7-B7-H3-KD cells were co-cultured with PBMCs, the proliferation ability of CD4+ T cells and CD8+ T cells was significantly higher than that observed in MCF7-Gapdh cell co-culture. Additionally, co-culture with MCF7-Gapdh cells decreased the expression of IFN-γ (Interferon-γ). However, after co-culture with MCF7-B7-H3-KD cells, there was an increase in IFN-γ. We further found that this inhibitory effect on IFN-γ was because of decreased mTOR (the mammalian target of rapamycin) phosphorylation in T cells. Treatment of T cells co-cultured with MCF7-B7-H3-KD cells with an mTOR inhibitor blocked the secretion of IFN-γ. B7-H3 on tumour cells inhibits the proliferation of CD4+ and CD8+ T cells and inhibits the release of IFN-γ by decreasing mTOR signalling. A better understanding of these complex immune regulatory mechanisms should facilitate the generation of more powerful and selective tools to manipulate cancer therapy. [ABSTRACT FROM AUTHOR]