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Hypertrophic scars (HTS) and keloids are challenging problems. Their pathogenesis results from an overproduction of fibroblasts and excessive deposition of collagen. Studies suggest a possible anti-scarring effect of basic fibroblast growth factor (bFGF) during wound healing, but the precise mechanisms of bFGF are still unclear. In view of this, we investigated the therapeutic effects of bFGF on HTS animal model as well as human scar fibroblasts (HSF) model. We show that bFGF promoted wound healing and reduced the area of flattened non-pathological scars in rat skin wounds and HTS in the rabbit ear. We provide evidence of a new therapeutic strategy: bFGF administration for the treatment of HTS. The scar elevation index (SEI) and epidermal thickness index (ETI) was also significantly reduced. Histological reveal that bFGF exhibited significant amelioration of the collagen tissue. bFGF regulated extracellular matrix (ECM) synthesis and degradation via interference in the collagen distribution, the α-smooth muscle actin (α-SMA) and transforming growth factor-1 (TGF-β1) expression. In addition, bFGF reduced scarring and promoted wound healing by inhibiting TGFβ1/SMAD-dependent pathway. The levels of fibronectin (FN), tissue inhibitor of metalloproteinase-1 (TIMP-1) collagen I, and collagen III were evidently decreased, and matrix metalloproteinase-1 (MMP-1) and apoptosis cells were markedly increased. These results suggest that bFGF possesses favorable therapeutic effects on hypertrophic scars in vitro and in vivo, which may be an effective cure for human hypertrophic scars. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HTS) and keloids are challenging problems. Their pathogenesis results from an overproduction of fibroblasts and excessive deposition of collagen. Studies suggest a possible anti-scarring effect of basic fibroblast growth factor (bFGF) during wound healing, but the precise mechanisms of bFGF are still unclear. In view of this, we investigated the therapeutic effects of bFGF on HTS animal model as well as human scar fibroblasts (HSF) model. We show that bFGF promoted wound healing and reduced the area of flattened non-pathological scars in rat skin wounds and HTS in the rabbit ear. We provide evidence of a new therapeutic strategy: bFGF administration for the treatment of HTS. The scar elevation index (SEI) and epidermal thickness index (ETI) was also significantly reduced. Histological reveal that bFGF exhibited significant amelioration of the collagen tissue. bFGF regulated extracellular matrix (ECM) synthesis and degradation via interference in the collagen distribution, the α-smooth muscle actin (α-SMA) and transforming growth factor-1 (TGF-β1) expression. In addition, bFGF reduced scarring and promoted wound healing by inhibiting TGFβ1/SMAD-dependent pathway. The levels of fibronectin (FN), tissue inhibitor of metalloproteinase-1 (TIMP-1) collagen I, and collagen III were evidently decreased, and matrix metalloproteinase-1 (MMP-1) and apoptosis cells were markedly increased. These results suggest that bFGF possesses favorable therapeutic effects on hypertrophic scars in vitro and in vivo, which may be an effective cure for human hypertrophic scars. [ABSTRACT FROM AUTHOR]

The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury. The protective effect of NGF is associated with the inhibition of autophagy related proteins. On another hand, NGF enhances the clearance of ubiquitinated protein and increases the survival of myocardial cell in vivo and in vitro. Additionally, NGF could activate the PI3K/AKT and mTOR signaling pathways. These results suggested that the cardioprotective effect of NGF is related to the restoration of autophagic flux and attenuation of protein ubiquitination via the activation of PI3K/AKT and mTOR pathway.

Objective: To explore the effects of endoplasmic reticulum stress (ERS) related proteins and their mediated apoptosis in the formation of deep tissue injury of pressure ulcer in rats., Methods: Forty male Sprague-Dawley rats were divided into normal control group and groups A, B, C, D according to the random number table, with 8 rats in each group. Rats in group A were loaded with 22.47 kPa pressure with a special pressure apparatus for 2.0 h in the region over gracilis, and then unloaded for 0.5 h. Rats in group B were treated with the same manoeuvre as that in group A for 3 times in one day. Rats in groups C and D were treated with the same manoeuvre as that in group B for 2 and 3 days. Rats in normal control group were free from pressure loading. Rats in groups A, B, C, and D were sacrificed after pressure loading, and then the central part of pressure loaded muscular tissues were harvested for observation of histomorphological change with HE staining; apoptotic nucleoli per millimeter pressure loaded muscular tissue were counted with Hoechst 33258 staining; the levels of binding protein (BIP), protein disulfide isomerase (PDI), C/EBP homologous protein (CHOP), and caspase-12 were assessed with Western blotting (denoted as gray level ratio of target protein to GAPDH). The same parts of gracilis of rats in normal control group were harvested for determination of all the indexes as above. Data were processed with one-way analysis of variance, LSD-t test was applied for paired comparison., Results: (1) Histomorphological observation. Some pathological changes, including inflammatory cell infiltration, myofibers lysis, and vacuolar degeneration, etc. were observed in pressure loaded muscular tissue of rats in groups A, B, C, and D, but not in the same parts of gracilis muscle of rats in normal control group. Compared with those in normal control group [(2.7 ± 1.4) per millimeter muscular tissue], the number of apoptotic nuclei was significantly increased in pressure loaded muscular tissue of rats in groups A, B, C, and D [(14.5 ± 4.4), (11.0 ± 2.9) , (13.8 ± 5.1), (21.3 ± 6.0) per millimeter pressure loaded muscular tissue, with t values from 4.223 to 6.000, P values all below 0.01). (2) Western blotting. The protein expressions of BIP and PDI in rats of normal control group and groups A, B, C, D were respectively 0.64 ± 0.12, 1.20 ± 0.34, 1.59 ± 0.24, 1.17 ± 0.28, 1.44 ± 0.33; 0.48 ± 0.15, 0.61 ± 0.19, 1.23 ± 0.38, 0.37 ± 0.19, 0.29 ± 0.15, and they showed significant statistical difference (with F values respectively 5.32, 7.95, P < 0.05 or P < 0.01). The protein expressions of CHOP and caspase-12 in rats of normal control group and groups A, B, C, D were respectively 0.58 ± 0.18, 1.48 ± 0.27, 1.03 ± 0.21, 0.95 ± 0.30, 1.69 ± 0.34; 0.55 ± 0.12, 1.08 ± 0.31, 0.69 ± 0.24, 1.79 ± 0.20, 2.06 ± 0.47, with significant statistical difference (with F values respectively 8.17, 15.48, P values all below 0.01)., Conclusions: ERS related proteins and their apoptotic pathway may play an important role in the formation of deep tissue injury of pressure ulcer in rats.