Effectiveness of platelet rich plasma in burn wound healing: a systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy of platelet-rich plasma (PRP) in the treatment of burn wounds. METHODS: A comprehensive literature survey was conducted in electronic medical journal databases to identify studies that examined the effect of PRP treatment to burn wounds and meta-analyses of mean differences (MD) standardized MD, or odds ratios were performed. RESULTS: The percentage of graft take was not significantly different between PRP-treated and control wound areas. Healing rate was significantly better in PRP-treated wounds. Healing time was also significantly less in PRP-treated wounds. There was no significant difference between PRP-treated and control wound areas in epithelialization or in the incidence of adverse events. Incidence of infection was also not different between PRP-treated and control wound areas. Scar assessment score was significantly better in PRP-treated than in control wound areas. CONCLUSION: PRP treatment to burn wounds is found to improve healing. Variations in study design and sample size, types of wounds, PRP preparation protocols, and high risk of bias in some of the included studies may have impact on these outcomes.

TIMP3/TGF­ß1 axis regulates mechanical loading­induced chondrocyte degeneration and angiogenesis.

Chondrocytes in injured cartilage tissue are susceptible to mechanical loading; mechanical overloading can induce cartilage degeneration. The aim of the present study was to investigate whether mechanical loading can regulate chondrocyte degeneration and angiogenesis via the tissue inhibitor of matrix metalloproteinase­3 (TIMP3)/transforming growth factor (TGF)­ß1 axis. Primary human chondrocytes were obtained from knee articular cartilage of a healthy donor. Then, normal chondrocytes or TIMP3 lentivirus­transfected (LV­TIMP3) chondrocytes were subjected to mechanical loading (10 MPa compression). Then, chondrocytes were stimulated with 1 µg/ml lipopolysaccharide (LPS) or treated with LDN­193189 (inhibitor of TGF­ß1 signaling pathway). In addition, human umbilical vein endothelial cells (HUVECs) were co­cultured with chondrocytes or LV­TIMP3 chondrocytes. The expression levels of collagen­I, proteoglycan, TIMP3, TGF­ß1, Smad2 and Smad3 were detected by reverse transcription­quantitative PCR and western blotting. Moreover, cell apoptosis and viability were determined using flow cytometry and MTT analysis, while cell migration was observed by Transwell assays. In addition, the vascular endothelial growth factor (VEGF)/VEGF receptor (R)2 binding rate in HUVECs was detected by a solid­phase binding assay. It was demonstrated that mechanical loading significantly inhibited the expression levels of collagen­I and proteoglycan in chondrocytes, as well as reducing cell proliferation and promoting cell apoptosis. In addition, the expression levels of TIMP3, TGF­ß1, phosphorylated (p)­Smad2 and p­Smad3 were significantly decreased in degenerated chondrocytes that were induced by LPS, as well as in chondrocytes treated with LDN­193189. Furthermore, TIMP3 overexpression suppressed cell migration and reduced the VEGF/VEGFR2 binding rate in HUVECs. Mechanical loading significantly inhibited the expression levels of TIMP3, TGF­ß1, p­Smad2 and p­Smad3 in chondrocytes, and also increased cell migration of HUVECs; TGF­ß1 treatment or TIMP3 overexpression reversed these effects. Thus, the TIMP3/TGF­ß1 axis may be a vital signaling pathway in mechanical loading­induced chondrocyte degeneration and angiogenesis.

microRNA-26a Directly Targeting MMP14 and MMP16 Inhibits the Cancer Cell Proliferation, Migration and Invasion in Cutaneous Squamous Cell Carcinoma.

PURPOSE: To investigate the specific effect and underlying mechanism of microRNA-26a-5p (miR-26a) in cutaneous squamous cell carcinoma (CSCC). METHODS: miR-26a and MMP14/16 mRNA expression were detected by qRT-PCR analysis. Functional experiments were used to detect the role of miR-26a on CSCC progression. Western blot was used for protein detection. Luciferase assay was used to detect miR-26a directly targeting MMP14 and MMP16. Xenograft nude mice model was used to determine the effect of miR-26a on tumorigenesis. RESULTS: miR-26a was decreased in CSCC tissues and cells. Forced miR-26a suppressed the progression of SCL-1 and A431 cells. Furthermore, miR-26a directly targeted MMP14 and MMP16 to inhibit their expression. Forced expression of MMP14 and MMP16 removed the miR-26a's inhibitory effect on CSCC development. The in vivo tumor growth assay showed that miR-26a suppressed CSCC tumorigenesis by targeting MMP14 and MMP16. CONCLUSION: Our study suggested miR-26a inhibits cancer cell proliferation, migration and invasion in CSCC by targeting MMP14 and MMP16.

Suppression of MicroRNA-383 Enhances Therapeutic Potential of Human Bone-Marrow-Derived Mesenchymal Stem Cells in Treating Spinal Cord Injury via GDNF.

BACKGROUND/AIMS: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) has been used to treat spinal cord injury (SCI) to enhance tissue repair and neural cell regeneration. Glial cell line derived neurotrophic factor (GDNF) is an identified neural growth and survival factor. Here, we examined whether modification of GDNF levels in MSCs may further increase the potential of MSCs in promoting neural cell regeneration and subsequently the therapeutic outcome. METHODS: We examined the mRNA and protein levels of GDNF in human MSCs by RT-qPCR and Western blot, respectively. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target GDNF in MSCs. The functional binding of miRNAs to GDNF mRNA was examined by a dual luciferase reporter assay. MSCs were transduced with adeno-associated virus (AAV) carrying null or antisense for miR-383 (as-miR-383), which were transplanted into nude rats that underwent SCI. The intact tissue, cavity volume, and recovery of locomotor activity were assessed. RESULTS: MSCs expressed very low GDNF protein, but surprisingly high levels of GDNF mRNA. Bioinformatics analyses showed that miR-383 inhibited protein translation of GDNF, through binding to the 3'-UTR of the GDNF mRNA. MSCs transduced with AAV-as-miR-383 further increased the intact tissue percentage, decreased cavity volume, and enhanced the recovery of locomotor activity in nude rats that underwent SCI, compared to MSCs. CONCLUSIONS: Suppression of miR-383 may increase the therapeutic potential of human bone-marrow-derived MSCs in treating SCI via augmentation of GDNF protein levels.