scholarly journals Identification of Specific miRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression ofmiRNA-129-2-3pAccelerates Diabetic Wound Healing

Diabetes ◽  
2018 ◽  
Vol 68 (3) ◽  
pp. 617-630 ◽  
Author(s):  
Takahiro Umehara ◽  
Ryoichi Mori ◽  
Kimberly A. Mace ◽  
Takehiko Murase ◽  
Yuki Abe ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiren Jiao ◽  
Xiaolin Chen ◽  
Yongxia Niu ◽  
Sunxing Huang ◽  
Jingwen Wang ◽  
...  

Abstract Background Diabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton’s jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored. Methods Firstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay. Results In diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo. Conclusion PF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.


Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 920
Author(s):  
Jingjuan Huang ◽  
Jia Fu ◽  
Bing Liu ◽  
Rui Wang ◽  
Tianhui You

The impairment in diabetic wound healing represents a significant clinical problem, with no efficient targeted treatments for these wound disorders. Curcumin is well confirmed to improve diabetic wound healing, however, its low bioavailability and poor solubility severely limit its clinical application. This study aims to provide the pharmacological basis for the use of (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66). The results showed that topically applied C66 improved cutaneous wound healing in vivo. Further studies showed that C66 treatment increased the level of microRNA-146a (miR-146a) in the wounds in streptozotocin (STZ)-induced diabetic mice, downregulated the expression of interleukin-1 receptor-associated kinase 1 (IRAK1) and phosphorylated nuclear factor-κB (NF-κB) p65 subunit (p-p65) (both p < 0.05), and suppressed the mRNA expression of inflammation-related cytokines, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6). The in vitro data obtained in human umbilical vein endothelial cells (HUVECs) showed that C66 could reverse high glucose (HG)-induced NF-κB activation due to upregulation of miR-146a expression, which matched the in vivo findings. In conclusion, the present study indicates that C66 exerts anti-inflammation activity and accelerates skin wound healing of diabetic mice, probably via increasing miR-146a and inhibiting the NF-κB-mediated inflammation pathway. Therefore, C66 may be a promising alternative for the treatment of diabetic wounds.


2016 ◽  
Vol 58 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Saeka Mochizuki ◽  
Mayuko Takano ◽  
Naoyuki Sugano ◽  
Mariko Ohtsu ◽  
Kou Tsunoda ◽  
...  

2019 ◽  
Vol 15 (2) ◽  
pp. 81
Author(s):  
Eka Sakti Wahyuningtyas ◽  
Nasruddin Nasruddin ◽  
Heni Setyowati Esti Rahayu ◽  
Heni Lutfiyati ◽  
Isabella Meliawati Sikumbang ◽  
...  

The continued increase in the number of people with Diabetes Mellitus (DM) in Indonesia is a serious problem. One of the big problems for people with Diabetes Mellitus (DM) is the emergence of complications of diabetic wounds. To date the strategy for treatment of diabetic wounds has been limited to the use of wound dressing, cell therapy and oxygen therapy. The problem is that the strategy is not fully successful. Thus, it is very important to look for new strategies to improve the quality of diabetic wound healing, such as by applying a combination of plasma medicine and local natural product, like the extraction of Daun sirih (Piper betle) leaves. Plasma medicine is a relatively new and multidisciplinary study involving plasma science, biomedical, pharmaceutical and other health sciences aimed at applying plasma to therapeutic health. Plasma is the fourth phase of matter, after the solid, liquid and gas phase. The medical aspects of plasma are related to the ability of plasma to produce biological molecules Reactive Oxygen and Nitrogen Species (RONS). If RONS is controlled in the right dosage it can be efficacious for health therapy. This study intends to examine the effects of combinative treatment of plasma medicine and Piper betel leaf extract for proliferation phase of wound healing in diabetic small animal model. This study used male Balb c mice with acute wounds which were divided into 5 groups, namely groups of untreated normal mice (ND-TP), groups of untreated diabetic mice (D-TP), groups of diabetic mice wounds with Piper betel leaf extract (DS ), the wound group of diabetic mice with plasma medicine (DP) and the wound group of diabetic mice with plasma medicine and Piper betel leaf (DPS). The plasma medicine was treated on wound with condition non-contact style (the plasma jet did not touch the wound) with a distance of plasma jet reactor nozzle to the surface of wound about 20 mm, for 2 minutes, every day. Macroscopic observation of wounds is carried out every day from day 0 to 7. On day 7 it was seen that the size of the wound area for D-P-S was smaller than the other groups. The results of this study indicated that Piper betel leaf extract can potentially be used to optimize the performance of plasma medicine in accelerating diabetic wound healing during the proliferation phase. Further investigation, however, is important to be conducted to study the effect for all phases of wound healing and its mechanism histo-pathologically.


2020 ◽  
Author(s):  
Guang-Huar Young ◽  
Jiun-Tsai Lin ◽  
Yi-Fang Cheng ◽  
Chia-Fang Ho ◽  
Qian-Yu Kuok ◽  
...  

AbstractAdenine phosphoribosyltransferase (APRT) is the key enzyme in purine salvage by the incorporation of adenine and phosphoribosyl pyrophosphate to provide adenylate nucleotide. The up-regulated APRT found in wound skin correlated with the demands of repair in diabetic mice. Administration of adenine on the wound of diabetic mice exhibited elevated ATP levels in organismic skin and accelerated wound healing. In vitro studies showed that APRT utilized adenine to rescue cellular ATP levels and proliferation against hydrogen peroxide-induced oxidative damage. LC-MS/MS-based analysis of total adenylate nucleotides in NIH-3T3 fibroblast showed that adenine addition enlarged the cellular adenylate pool, reduced the adenylate energy charge, and provided more AMP for the generation of ATP in further. These data indicated the role of APRT during diabetic wound healing by regulating the nucleotide pool after injury and demonstrated the improvement by topical adenine, which highlights its value as a promising agent in therapeutic intervention. Our study provided an explanation for the up- regulation of APRT in tissue repair and adenine supplement resulted in an enlargement of the adenylate pool for ATP generation.


2018 ◽  
Vol 61 (4) ◽  
pp. 163-172 ◽  
Author(s):  
Ying Li ◽  
Fuzhe Ma ◽  
Huimin Li ◽  
Yuguo Song ◽  
Huan Zhang ◽  
...  

Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) – a master of cellular antioxidants scavenging excessive DM-induced free radicals – in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation and accelerated wound closure in diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG) or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) – inducible in DM – in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing.


2014 ◽  
Vol 307 (11) ◽  
pp. C1058-C1067 ◽  
Author(s):  
Song Hong ◽  
Haibin Tian ◽  
Yan Lu ◽  
James Monroe Laborde ◽  
Filipe A. Muhale ◽  
...  

Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10 R,17 S-dihydroxy-docosa-4 Z,7 Z,11 E,13 E,15 Z,19 Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MΦs from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MΦs. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MΦs functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MΦs involved 1) attenuating MΦ inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MΦ production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MΦs-produced factor that accelerates diabetic wound healing and promotes MΦ pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MΦs for treatment of diabetic wounds.


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