Combination of chemically modified SDF-1α mRNA and small skin improves wound healing in diabetic rats with full-thickness skin defects.

OBJECTIVES: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA. MATERIALS AND METHODS: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. RESULTS: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro. CONCLUSIONS: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.

Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats.

Random skin flaps are frequently applied in plastic and reconstructive surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential. Here, we explored the potential of fibroblasts engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) to improve vascularization and survival of therapeutic random skin flaps. Our study showed that fibroblasts pre-treated with SDF-1α modRNA have the potential to salvage ischemic skin flaps. Through a detailed analysis, we revealed that a fibroblast SDF-1α modRNA combinatorial treatment dramatically reduced tissue necrosis and significantly promoted neovascularization in random skin flaps compared to that in the control and vehicle groups. Moreover, SDF-1α modRNA transcription in fibroblasts promoted activation of the SDF-1α/CXCR4 pathway, with concomitant inactivation of the MEK/ERK, PI3K/AKT, and JAK2/STAT3 signaling pathways, indicating a possible correlation with cell proliferation and migration. Therefore, fibroblast-mediated SDF-1α modRNA expression represents a promising strategy for random skin flap regeneration.

Scutellarin Attenuates the IL-1ß-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression.

Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In in vitro assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) via qRT-PCR and Western blotting, the expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were detected by qRT-PCR. Our results showed that the downregulation of MMP-13, ADAMTS-5, COX-2, and iNOS expression by SCU and the overproduction of IL-6, TNF-α, and PGE2 induced by IL-1ß were all inhibited by SCU in a concentration-dependent manner. Moreover, SCU was able to reverse aggrecan and collagen II degradation and nuclear factor-κB (NF-κB) and nuclear factor erythroid-derived 2-like 2 (Nrf2) signaling pathway activation both in vivo and in vitro. We further used a destabilization of the medial meniscus (DMM) murine model of OA to explore the therapeutic benefits of SCU in vivo. Together, our findings suggest SCU to be a potentially valuable therapeutic agent useful for treating OA.

Microvascular Replantation of Totally Avulsed Scalps: Failures and Successes.

Total scalp avulsion is a rare but devastating injury currently without proven reconstructive techniques. While microsurgical anastomosis procedures have advanced and allowed for the replantation of digits and limbs, special anatomical considerations and risk of fatal blood loss add to the difficulty of replanting totally avulsed scalps. The authors present their replantation experience of 4 totally avulsed scalps between 2008 and 2017. Despite meticulous reconstructive techniques with proven success in limb and digit replantation, the first 3 cases failed due to various factors (i.e., thrombosis, venous congestion, reavulsion), and with experience, the fourth case was successful. Since total scalp avulsions are rare injuries, case reports are scarce, with only few publications commenting on failures which hold crucial information for surgeons to avoid pitfalls and optimize techniques. In this article, we highlight our experience with both successful and failed replantation of totally avulsed scalps, and offer recommendations and insight for optimization of this rare procedure.

Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review.

BACKGROUND: We have previously proved that treatment of thick/deep infantile hemangiomas (IHs) with a long-pulse Alexandrite laser was clinically effective and safe. This article aims to investigate the efficiency of long-pulse Alexandrite laser use in treating thick and high-risk IHs located in particular anatomic areas and provides some new data on this issue. CASE SUMMARY: A two-month-old girl with a thick and high-risk IH covering most of the right labia majora was examined in this study. The infant received four treatment sessions at 4- to 6-wk intervals with a long-pulse Alexandrite laser with settings as follows: 3 ms pulse duration, 8 mm spot size, 45 to 50 J/cm2 fluences, and dynamic cooling device (DCD) spray duration of 90 ms with a delay of 80 ms. Following each of the four treatment sessions, the IH showed a remarkable reduction in thickness and size without any sign of relapse. Ten months after the last treatment, the IH had completely regressed without adverse effects. During the laser treatment, no severe side effects were observed; blistering occurred only immediately after treatment and then scabbed over the next day, gradually improving in the following days. CONCLUSION: Long-pulse Alexandrite laser treatment may be considered one of the first-line noninvasive therapeutic options for the treatment of thick IH.

The Protective Effect of Magnolol in Osteoarthritis: In vitro and in vivo Studies.

Osteoarthritis (OA), defined as a long-term progressive joint disease, is characterized by cartilage impairment and erosion. In recent decades, magnolol, as a type of lignin extracted from Magnolia officinalis, has been proved to play a potent anti-inflammatory role in various diseases. The current research sought to examine the latent mechanism of magnolol and its protective role in alleviating the progress of OA in vivo as well as in vitro experimentations. In vitro, the over-production of Nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6), induced by interleukin-1 beta (IL-1ß), were all inhibited notably by magnolol in a concentration-dependent manner. Moreover, magnolol could also downregulate the expression of metalloproteinase 13 (MMP13) and thrombospondin motifs 5 (ADAMTS5). All these changes ultimately led to the deterioration of the extracellular matrix (ECM) induced by IL-1ß. Mechanistically, magnolol suppressed the activation of PI3K/Akt/NF-κB pathway. Furthermore, a powerful binding capacity between magnolol and PI3K was also revealed in our molecular docking research. In addition, magnolol-induced protective effects in OA development were also detected in a mouse model. In summary, this research suggested that magnolol possessed a new therapeutic potential for the development of OA.

Routine closure of the donor site with a second dorsal metacarpal artery flap to avoid the use of a skin graft after harvest of a first dorsal metacarpal artery flap.

AIM: Closure of the donor site on the index finger after raising a first dorsal metacarpal artery (DMA) flap harvest is challenging. The conventional choice is to use a full-thickness skin graft. However, this procedure is associated with several complications and a second donor site to harvest the skin graft is inevitable. The aim of this study was to design a modified incision to allow harvest of a first DMA flap without skin graft. METHODS: From 2015 to 2016, 18 patients with a soft tissue defect of the thumb had reconstruction of the defect using a first DMA flap. A modified incision was used and a relaying perforator flap pedicled on the second DMA was raised through the same incision to cover the donor site. Patient satisfaction, appearance of the injured hand, and the active range of motion (ROM) were assessed. The sensitivity was evaluated by the 2-point discrimination (2-PD) test. RESULTS: All flaps survived completely without complications. Good coverage was obtained with only one linear scar in the dorsum of the hand and no skin grafts. All patients recovered full range of movement in their fingers and regained sensitivity of the flaps. All patients were satisfied with their hand function according to the Michigan Hand Outcomes Questionnaire (MHQ). The mean cosmetic score for the appearance of the injured hand was 8.2 out of 10. CONCLUSIONS: Using our modified incision, it was possible to harvest a second DMA flap at the same time as a first DMA flap allowing simultaneous coverage of the donor defect on the index finger. This prevented the need for a skin graft with all of the associated disadvantages.

Repair of articular cartilage defects with acellular cartilage sheets in a swine model.

Acellular cartilage sheets (ACSs) have been demonstrated as a good biomaterial for cartilage regeneration as a result of their natural cartilage matrix components, cartilage-specific structures, and good biocompatibility. However, it remains unknown whether allogeneic ACSs could promote cartilage regeneration and repair cartilage defects in a large animal model. The current study explored the feasibility of repairing articular cartilage defects using ACS scaffold with or without autologous bone marrow stromal cells (BMSCs) in a swine model. According to the current results, ACSs retained natural cartilage structure, primary cartilage matrices, and cartilage-specific growth factors. After cell seeding, ACSs presented good biocompatibility with BMSCs, which produced abundant extracellular matrix (ECM) proteins to cover the lacuna structures. In vivo results indicated that ACSs alone could induce endogenous host cells to regenerate cartilage and achieve generally satisfactory repair of cartilage defects at 6 months post-operation, including good interface integration and cartilage-specific ECM deposition. After combination with autologous BMSCs, BMSC-ACS constructs achieved more satisfactory repair of cartilage defects even without in vitro pre-induction of chondrogenesis. More importantly, all defects in both BMSC-ACS and ACS-only groups showed enhanced cartilage regeneration compared with BMSC-polyglycolic acid and blank groups, which mainly exhibited fibrogenesis in defect areas. Collectively, the current results indicate that ACSs can efficiently repair articular cartilage defects by promoting chondrogenic differentiation of BMSCs or inducing endogenous chondrogenesis in situ, thus serving as a good cartilage regeneration scaffold for recovery of articular function.

Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus vulgaris: a preliminary study.

IL-23/IL-17 axis has been identified as major factor involved in the pathogenesis of several autoimmune diseases; yet its pathogenetic role in pemphigus vulgaris (PV) remains controversial. The aim of this research was to investigate the potential role of IL-23/IL-17 axis in the immunopathogenesis of PV, and correlation between IL-23+ cells and IL-17+ cells was also evaluated. For this purpose, ten patients with PV, three patients with pemphigus foliaceus (PF), and six healthy individuals were allocated to this research. The lesional skin biopsy specimens were obtained before treatment. Then immunofluorescence staining was performed to analyze the expression of IL-23 and IL-17 in the PV/PF patients and the healthy individuals. The results showed that the numbers of IL-23+ and IL-17+ cells were significantly higher in PV lesions, compared to PF lesions and normal control skins, respectively (all P < 0.05). Moreover, the correlation between IL-23+ cells and IL-17+ cells was significant (r = 0.7546; P < 0.05). Taken together, our results provided evidence that the IL-23/IL-17 axis may play a crucial role in the immunopathogenesis of PV and may serve as novel therapeutic target for PV.

Beneficial effects of early treatment of infantile hemangiomas with a long-pulse Alexandrite laser.

BACKGROUND AND OBJECTIVE: There is an increasing interest in treating vascular lesions with a long-pulse Alexandrite laser. However, it is difficult to search information in the literature about infantile hemangiomas (IH) treated with long-pulse Alexandrite laser. This article aims to determine whether 755 nm long-pulse Alexandrite laser is effective and safe for early intervention of IH and provides some new data on this issue. MATERIALS AND METHODS: This is a retrospective study of 48 infants with IH treated with long-pulse Alexandrite laser during a 1.5-year period. Patients received a series of 1-7 treatment sessions with long-pulse Alexandrite laser at settings of 3 milliseconds pulse duration, 6-8 mm spot, 45-70 J/cm(2) fluences, and with dynamic cooling device (DCD) spray duration of 90 milliseconds and delay of 80 milliseconds, given at 4- to 6-week intervals. RESULTS: This study demonstrated that IH responded favorably to the treatment of a long-pulse Alexandrite laser while accompany with relatively few complications. The difference between the original untreated and post-treatment scores of all IH and two subgroups were statistically significant, respectively (P < 0.01). The difference of the degree of improvement between the two subgroups was not significant (P > 0.05). It was observed that IH on the trunk and extremities improved more effectively and more quickly than those on the face, neck, and perineum. Besides, age at the first treatment, the sex of the patients and the presence of proliferation were not significantly correlated with the degree of improvement. Adverse effects were seen in 11 patients (22.91%): blistering (n = 9), marked edema and erosion without subsequent residual scarring (n = 1), and hypopigmentation (n = 1), which improved gradually with time. Fortunately, there was no incidence of scarring or ulceration in this case series of IH. CONCLUSIONS: It was clinically effective and safe for early treatment of IH, including the thick/deep ones, with a long-pulse Alexandrite laser, which indicated be able to reduce the possibility that the IH will reach its full size. In this way it can prevent several complications connected to the rapid proliferation of IH.