Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2.

Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. METHODS: C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. RESULTS: This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. CONCLUSION: This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.

A retrospective study on comparing the surgery and microneedles radiofrequency and microwaves treatment in axillary osmidrosis.

OBJECTIVE: To compare the traditional treatment of minimally invasion surgery with the evolving treatments of microneedles radiofrequency and microwaves, this study mainly focused on the clinical efficacy and the incidence rate (IR) of complications among three treatments. METHODS: From August 2017 to August 2018, a total of 76 patients with bilateral axillary osmidrosis were enrolled respectively underwent minimally invasion surgery, microneedles radiofrequency and microwaves treatment. All these subjects were evaluated the clinical outcomes and collected the complications by themselves or physicians. The difference of objective recovery or effective rate, subjective effective rate, the intense of sweat secretion or armpits hair, IR of complications among these three groups were studied. RESULTS: The baseline characteristics of 33 patients in surgery group, 24 patients in microneedles group and 19 patients in microwaves group were similar. Firstly, the objective clinical efficacy was similar, but the subjective effective rate in surgery group was the soundest. In addition, the reduction of sweat secretion was homologous in three group, but the intense of armpits hair reduction in microneedles group was the minimum in three groups. Moreover, surgery treatment caused the highest IR of complications and the broadest types of complications, especially for the IR of 87.9% in postoperative scar formation. Meanwhile, the microwaves treatment had the best safety profile. At last, the recurrence rate on 6 months postoperatively was also identical with no significant difference. CONCLUSIONS: For the advantages and disadvantages of these three treatments, axillary osmidrosis patients should choose the proper therapy with comprehensive considerations.

Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection.

Activated γδ T cells have been shown to accelerate allograft rejection. However, the precise role of skin-resident γδ T cells and their subsets-Vγ5 (epidermis), Vγ1, and Vγ4 (dermis)-in skin graft rejection have not been identified. Here, using a male to female skin transplantation model, we demonstrated that Vγ4 T cells, rather than Vγ1 or Vγ5 T cells, accelerated skin graft rejection and that IL-17A was essential for Vγ4 T-cell-mediated skin graft rejection. Moreover, we found that Vγ4 T cells were required for early IL-17A production in the transplanted area, both in skin grafts and in the host epidermis around grafts. Additionally, the chemokine (C-C motif) ligand 20-chemokine receptor 6 pathway was essential for recruitment of Vγ4 T cells to the transplantation area, whereas both IL-1ß and IL-23 induced IL-17A production from infiltrating cells. Lastly, Vγ4 T-cell-derived IL-17A promoted the accumulation of mature dendritic cells in draining lymph nodes to subsequently regulate αß T-cell function after skin graft transplantation. Taken together, our data reveal that Vγ4 T cells accelerate skin graft rejection by providing an early source of IL-17A.

Identification of ITGB4BP as a new interaction protein of P311.

AIMS: P311 is an 8 kDa protein that has been shown to be of importance in the process of myofibroblast transformation, glioblastoma invasion and nerve regeneration. However, the interaction protein of P311 has yet to be found. The purpose of this study was to find the interactive protein of P311. MAIN METHODS: The yeast two-hybrid system was used for screening the potential interaction proteins of P311. Joint expression of the potential interactive protein and P311 was immunohistochemically stained. The interaction between P311 and the selected protein was further confirmed by fluorescence resonance energy transfer (FRET) in pulmonary adenocarcinoma tissue sections, and by coimmunoprecipitation in HEK293. KEY FINDINGS: Integrin ß4 binding protein (ITGB4BP) was confirmed as the interaction protein of P311. Co-expression and interaction of ITGB4BP and P311 were demonstrated in pulmonary adenocarcinoma by both immunohistochemistry and FRET. Moreover the interaction between P311 and ITGB4BP was demonstrated by coimmunoprecipitation in HEK293. SIGNIFICANCE: The interactions between P311 and ITGB4BP may be very important in the process of tumor cell differentiation and metastasis. ITGB4BP may provide a potential new target for the therapy of tumors.

Embryonic porcine skin precursors can successfully develop into integrated skin without teratoma formation posttransplantation in nude mouse model.

How to improve the wound healing quality of severe burn patients is still a challenge due to lack of skin appendages and rete ridges, no matter how much progress has been made in the fields of either stem cell or tissue engineering. We thus systematically studied the growth potential and differentiation capacity of porcine embryonic skin precursors. Implantation of embryonic skin precursors (PESPs) of different gestational ages in nude mice can generate the integrity skin, including epidermis, dermis and skin appendages, such as sweat gland, hair follicle, sebaceous gland, etc.. PESPs of embryonic day 42 possess the maximal growth potential, while, the safe window time of PESPs transplantation for prevention of teratoma risk is E56 or later. In conclusion, PESPs can form the 3 dimensional structures of skin with all necessary skin appendages. Our data strongly indicate that porcine embryonic skin precursors harvested from E56 of minipig may provide new hope for high-quality healing of extensive burns and traumas.

[The study in immunology after skin transplantation].

Skin grafting has been one of the most important approaches for covering burn wounds, however long-term survival of allogeneic or xenogeneic skin graft is currently not successful. How to induce immune tolerance for life-time survival of allogeneic or xenogeneic skin graft is still remote objective to be solved. However, clinicians and scientists in China have worked very hard and made great contribution to this field during the past 50 years, no matter how difficult it is. They are the respected pioneers in the understanding of immunological change in "Chinese Method" skin grafting, its local immune tolerance, immunology of pre-treatment of skin graft, etc. Herein, the most outstanding and impressive progresses in immunological responses after skin grafting in the past 50 years in China have been reviewed and presented for memory, for future and for extending a salute.

[Study of xenotransplantation of fetal pig skin precursor tissue].

OBJECTIVE: To select the optimal pregnancy time window of embryonic pig skin precursor tissue for xenotransplantation and study its ability in wound repair. METHODS: Skin precursor tissues were obtained from pig fetus of fetal age of 35, 42, 56, 70 days, and were minced into microskin and transplanted to dorsal wounds of BALB/c nude mice, then they were covered with residual skin after plastic surgery of patients or adult pig skin (white). The characteristics of growth and development were observed after transplantation. Pathological examination was performed on 6 and 12 post operation weeks respectively to observe the tissue structure and tumorigenicity. RESULTS: Skin precursor tissues from fetal pig survived and developed after transplantation, and the microskin fused. New tissue area from skin precursor tissues with fetal age of 42 days was (47 +/- 6) mm2, which was higher than that of 35 days (18 +/- 8 mm2), 56 days (31 +/- 12 mm2), 70 days (20 +/- 8 mm2, P < 0.05). The skin precursor developed into "intact skin" with hair, sebaceous glands and sweat glands, and melanocytes were also detected in epidermis. The newly-grown skin tissue included epidermal and dermal layer, and obvious dermal papillae. Teratoma was not found after transplantation in skin precursor tissue with fetal age of 56, 70 days. CONCLUSION: Fetal pig skin precursor tissue with fetal age of 56 days can be used to repair wound as xenotransplantation.