scholarly journals Proteomic Analysis of Peri-Wounding Tissue Expressions in Extracorporeal Shock Wave Enhanced Diabetic Wound Healing in a Streptozotocin-Induced Diabetes Model

2020 ◽  
Vol 21 (15) ◽  
pp. 5445 ◽  
Author(s):  
Rong-Fu Chen ◽  
Ming-Yu Yang ◽  
Ching-Jen Wang ◽  
Chun-Ting Wang ◽  
Yur-Ren Kuo

Our former studies have demonstrated that extracorporeal shock wave therapy (ESWT) could enhance diabetic wound healing but the bio-mechanisms remain elusive. This study investigated the changes of topical peri-wounding tissue expressions after ESWT in a rodent streptozotocin-induced diabetic wounding model by using the proteomic analysis and elucidated the molecular mechanism. Diabetic rats receiving ESWT, normal control, and diabetic rats receiving no therapy were analyzed. The spots of interest in proteome analysis were subjected to mass spectrometry to elucidate the peptide mass fingerprints. Protein expression was validated using immunohistochemical staining and related expression of genes were analyzed using real-time RT-PCR. The proteomic data showed a significantly higher abundance of hemopexin at day 3 of therapy but down-regulation at day 10 as compared to diabetic control. In contrast, the level of serine proteinase inhibitor (serpin) A3N expression was significantly decreased at day 3 therapy but expression was upregulated at day 10. Using real-time RT-PCR revealed that serpin-related EGFR-MAPK pathway was involved in ESWT enhanced diabetic wound healing. In summary, proteome analyses demonstrated the expression change of hemopexin and serpin with related MAPK signaling involved in ESWT-enhanced diabetic wound healing. Modulation of hemopexin and serpin related pathways are good strategies to promote wound healing.

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 21
Author(s):  
Rong-Fu Chen ◽  
Yun-Nan Lin ◽  
Keng-Fan Liu ◽  
Chun-Ting Wang ◽  
Savitha Ramachandran ◽  
...  

Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3β (GSK-3β) is involved in epithelial differentiation during wound healing. This study investigated whether the enhancement of diabetic wound healing by ESWT is associated with the GSK-3β-mediated Wnt/β-catenin signaling pathway. A dorsal skin wounding defect model using streptozotocin-induced diabetic rodents was established. Rats were divided into 4 groups: group 1, normal controls without diabetes; group 2, diabetic controls without treatment; group 3, diabetic rats receiving ESWT; and group 4, rats receiving 6-bromoindirubin-3′oxime (BIO), a GSK-3β inhibitor, to trigger Wnt/β-catenin signaling. Tissue samples were collected and analyzed by immunohistochemical (IHC) staining and quantitative RT-PCR. The ESWT and BIO-treated groups both exhibited significant promotion of wound healing compared to the healing in controls without treatment. RT-PCR analysis of Wnt-1, -3a, -4, -5a, and -10 and β-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and β-catenin levels were significantly increased in the ESWT and BIO treatment groups compared to the control groups. ESWT enhancement of diabetic wound healing is associated with modulation of the GSK-3β-mediated Wnt/β-catenin signaling pathway.


2011 ◽  
Vol 19 (5) ◽  
pp. 633-644 ◽  
Author(s):  
Zhifeng Huang ◽  
Meifei Lu ◽  
Guanghui Zhu ◽  
Hongchang Gao ◽  
Liyun Xie ◽  
...  

Nanomedicine ◽  
2019 ◽  
Vol 14 (22) ◽  
pp. 2909-2923 ◽  
Author(s):  
Shuaihua Li ◽  
Qiyu Tang ◽  
Hongbo Xu ◽  
Qiangru Huang ◽  
Zi Wen ◽  
...  

Aim: Diabetic wound healing is seriously interrupted, and administration of KGF for wound treatment is restricted by its inherent instability. We aim to develop an ideal way toward KGF stabilization, thus improving diabetic wound healing. Materials & methods: We conjugated KGF with gold nanoparticles (GNPs) and determined the stability and binding affinity. Biological effects of conjugates (KGF-GNPs) were evaluated in vitro and in an animal model. Results: KGF-GNPs revealed high stability under hostile circumstances because of the preserved secondary structure and possessed elevated binding affinity to KGF receptor. Moreover, application of KGF-GNPs contributed to accelerated wound recovery in diabetic rats, including re-epithelialization and contraction. Conclusion: KGF-GNPs were promising for future clinical application for diabetic wound therapy.


2011 ◽  
Vol 3 (3) ◽  
pp. 204
Author(s):  
Djanggan Sargowo ◽  
Adeodatus Yuda Handaya ◽  
Mohammad Aris Widodo ◽  
Diana Lyrawati ◽  
Askandar Tjokroprawiro

BACKGROUND: Diabetic micro and macroangiophathy lead to the incident of diabetic foot ulcers characterized by an increased number of circulating endothelial cells (CECs) and decreased function of endothelial progenitor cells (EPCs). This fact is correlated with ischemia and diabetic wound healing failure. Aloe vera gel is known to be able to stimulate vascular endothelial growth factor (VEGF) expression and activity by enhancing nitric oxide (NO) production as a result of nitric oxide synthase (NOS) enzyme activity. Aloe vera is a potential target to enhancing angiogenesis in wound healing.OBJECTIVE: The objective of this study was to explore the major role of Aloe vera gel in wound healing of diabetic ulcers by increasing the level of EPCs, VEGF, and endothelial nitric oxide synthase (eNOS), as well as by reducing the level of CECs involved in angiogenesis process of diabetic ulcers healing.METHODS: The experimental groups was divided into five subgroups consisting of non diabetic wistar rats, diabetic rats without oral administration of aloe gel, and treatment subgroup (diabetic rats) with 30, 60 and 120 mg/day of aloe gel doses for 14 days. All subgroups were wounded and daily observation was done on the wounds areas. Measurement of the number of EPCs (CD34), and CECs (CD45 and CD146) was done by flowcytometry, followed by measurement of VEGF and eNOS expression on dermal tissue by immunohistochemical method on day 0 and day 14 after treatment. The quantitative data were analyzed by One-Way ANOVA and Linear Regression, with a cofidence interval 5% and significance level (p<0.05) using SPSS 16 software to compare the difference and correlation between wound diameters, number of EPCs and CECs as well as the levels of VEGF and eNOS.RESULTS: The results of this study showed that aloe gel oral treatment in diabetic wistar rats was able to accelerate the wound healing process. It was shown by significant reduction of wound diameter (0.27±0.02); the increased number of CECs (0.42±0.57), respectively (p<0.05). On the other hand, the wound diameter and eNOS indicators showed significant differences at the dose of 60 mg, while the number of EPCs and CECs and the level of VEGF showed significantly different results at a dose of 120 mg. Aloe gel oral therapy showed a positive indication of wound healing acceleration at the optimum dose range 60-120 mg a day.CONCLUSIONS: Aloe gel is potential to be a herbal therapy candidate for diabetic wound healing through enhancing EPCs homing, decreasing the CECs number, and stimulating the increase of VEGF and eNOS levels,hence proving to be a dominant factor in the angiogenesis process.KEYWORDS: aloe gel, diabetes, wound healing, angiogenesis


Author(s):  
Samuel A. Akwetey ◽  
Douglas B. Aidoo ◽  
Wisdom Ahlidja ◽  
Bright B. Boafo ◽  
Joseph M. Acquah ◽  
...  

Background: This study evaluated the potential of Ziziphus abysinnica root extract in managing hyperglycaemia in type 2 diabetes mellitus (T2DM), diabetic wound healing and diabetic nephropathy. Methodology: Blood glucose concentrations were measured daily for 14 days after daily administrations of either Ziziphus abysinnica (30, 100, and 300 mg/kg, p.o), metformin (300 mg/kg, p.o) or normal saline as negative control before diabetes induction using a single dose of Streptozotocin (60 mg/kg, i.p) and nicotinamide (120 mg/kg, i.p). Histopathological analysis was performed on the harvested kidneys following administration with Ziziphus abysinnica in diabetic rats. The diabetic wound healing potentials of the plant was also evaluated in streptozotocin-induced diabetic rats by treating them with 15%w/w ZAE ointment. Results: Generally, the percentage of blood glucose levels analysed following administration of drugs were found to be dose-dependent. The highest dose of ZAE (300 mg/kg) had a higher percentage reduction in blood glucose concentration when compared to metformin (300 mg/kg).  The lowest dose (30 mg/kg) of ZAE administered attenuated STZ induced pathological damage and showed moderate to maximal improvement to the kidney nephrons. In contrast, the 100 mg/kg and 300 mg/kg dose ZAE demonstrated minimal pathological changes to the kidney architecture. Conclusion: Overall, our study demonstrated the antidiabetic potential of Ziziphus abysinnica, suggesting its possible therapeutic benefit in diabetic wound healing and diabetic nephropathy. 


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