scholarly journals A Synthetic Curcuminoid Analog, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone, Ameliorates Impaired Wound Healing in Streptozotocin-Induced Diabetic Mice by Increasing miR-146a

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 920
Author(s):  
Jingjuan Huang ◽  
Jia Fu ◽  
Bing Liu ◽  
Rui Wang ◽  
Tianhui You
Keyword(s):  
Wound Healing ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Skin Wound Healing ◽  
Promising Alternative ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

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.

scholarly journals Shedding Light on a New Treatment for Diabetic Wound Healing: A Review on Phototherapy

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Nicolette N. Houreld
Keyword(s):  
Wound Healing ◽  
Laser Irradiation ◽  
Diabetic Wound ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing ◽  
New Treatment ◽  
Underlying Mechanisms ◽  
Intensity Laser

Impaired wound healing is a common complication associated with diabetes with complex pathophysiological underlying mechanisms and often necessitates amputation. With the advancement in laser technology, irradiation of these wounds with low-intensity laser irradiation (LILI) or phototherapy, has shown a vast improvement in wound healing. At the correct laser parameters, LILI has shown to increase migration, viability, and proliferation of diabetic cellsin vitro; there is a stimulatory effect on the mitochondria with a resulting increase in adenosine triphosphate (ATP). In addition, LILI also has an anti-inflammatory and protective effect on these cells. In light of the ever present threat of diabetic foot ulcers, infection, and amputation, new improved therapies and the fortification of wound healing research deserves better prioritization. In this review we look at the complications associated with diabetic wound healing and the effect of laser irradiation bothin vitroandin vivoin diabetic wound healing.

scholarly journals Novel long non-coding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1

2020 ◽  
Author(s):  
Ada Admin ◽  
Mengdie Hu ◽  
Yuxi Wu ◽  
Chuan Yang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Diabetic Foot ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Delayed Wound Healing ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, w<a>e identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA <u>U</u>p<u>R</u>egulated <u>i</u>n <u>D</u>iabetic <u>S</u>kin), which regulates wound healing in diabetes mellitus. </a>Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment <i>in vitro</i> and accelerated diabetic wound healing <i>in vivo</i>. Mechanistically, <a>lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. </a><a>The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. </a><a>The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.</a>

scholarly journals Novel long non-coding RNA lnc-URIDS delays diabetic wound healing by targeting Plod1

2020 ◽  
Author(s):  
Ada Admin ◽  
Mengdie Hu ◽  
Yuxi Wu ◽  
Chuan Yang ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Wound Healing ◽  
Diabetic Foot ◽  
Dermal Fibroblasts ◽  
Diabetic Wound ◽  
Delayed Wound Healing ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

Impaired wound healing is one of the main reasons that leads to diabetic foot ulcerations. However, the exact mechanism of delayed wound healing in diabetes mellitus is not fully understood. Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes and diseases, including diabetes and its associated complications. Here, w<a>e identified a novel lncRNA MRAK052872, named lnc-URIDS (lncRNA <u>U</u>p<u>R</u>egulated <u>i</u>n <u>D</u>iabetic <u>S</u>kin), which regulates wound healing in diabetes mellitus. </a>Lnc-URIDS was highly expressed in diabetic skin and dermal fibroblasts treated with advanced glycation end products (AGEs). Lnc-URIDS knockdown promoted migration of dermal fibroblasts under AGEs treatment <i>in vitro</i> and accelerated diabetic wound healing <i>in vivo</i>. Mechanistically, <a>lnc-URIDS interacts with procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (Plod1), a critical enzyme responsible for collagen cross-linking. </a><a>The binding of lnc-URIDS to Plod1 results in a decreased protein stability of Plod1, which ultimately leads to the dysregulation of collagen production and deposition and delays wound healing. Collectively, this study identifies a novel lncRNA that regulates diabetic wound healing by targeting Plod1. </a><a>The findings of the present study offer some insight into the potential mechanism for the delayed wound healing in diabetes and provide a potential therapeutic target for diabetic foot.</a>

scholarly journals Dimethyl fumarate accelerates wound healing under diabetic conditions

2018 ◽  
Vol 61 (4) ◽  
pp. 163-172 ◽  
Author(s):  
Ying Li ◽  
Fuzhe Ma ◽  
Huimin Li ◽  
Yuguo Song ◽  
Huan Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oxidative Damage ◽  
Critical Role ◽  
Dimethyl Fumarate ◽  
Related Factor ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing

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.

scholarly journals Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiqiang Hu ◽  
Ranyang Tao ◽  
Lang Chen ◽  
Yuan Xiong ◽  
Hang Xue ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Diabetic Rat ◽  
Diabetic Wound ◽  
Ecm Remodeling ◽  
Diabetic Wound Healing

Abstract Background Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Results We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. Conclusions PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing. Graphic abstract

scholarly journals Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic mice by suppressing NF-κB-mediated inflammatory genes

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
YiFeng Yuan ◽  
Sushant K. Das ◽  
MaoQuan Li
Keyword(s):  
Vitamin D ◽  
Wound Healing ◽  
Inflammatory Responses ◽  
Vitamin D Supplementation ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Diabetic wounds are characterized by delayed wound healing due to persistent inflammation and excessive production of reactive oxygen species. Vitamin D, which is well acknowledged to enhance intestinal calcium absorption and increase in plasma calcium level, has recently been shown to display beneficial effects in various vascular diseases by promoting angiogenesis and inhibiting inflammatory responses. However, the role of Vitamin D in diabetic wound healing is still unclear. In the present study, we investigated the role of Vitamin D in cutaneous wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after injection of STZ, a full thickness excisional wound was created with a 6-mm diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation significantly accelerated wound healing in diabetic mice and improved the healing quality as assessed by measuring the wound closure rate and histomorphometric analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL) 6 (IL-6), IL-1β) in the wounds, reduced inflammatory response was found in VD treatment group. Furthermore, nuclear factor κB (NF-κB) pathway was found to be involved in the process of diabetic wound healing by assessing the relative proteins in diabetic wounds. Vitamin D supplementation obviously suppressed NF-κB pathway activation. These results demonstrated that Vitamin D improves impaired wound healing in STZ-induced diabetic mice through suppressing NF-κB-mediated inflammatory gene expression.

scholarly journals A low dose of simvastatin enhanced the therapeutic efficacy of mesenchymal stem cell (MSC) transplantation in skin wound healing in diabetic mice associated with increases in pAkt, SDF-1, and angiogenesis

2019 ◽  
Author(s):  
Supakanda Sukpat ◽  
Nipan Israsena ◽  
Jutamas Wongphoom ◽  
Praewphan Ingrungruanglert ◽  
Tao Ming Sim ◽  
...  
Keyword(s):  
Wound Healing ◽  
Therapeutic Efficacy ◽  
Wound Closure ◽  
Low Dose ◽  
Skin Wound ◽  
Diabetic Wound ◽  
Diabetic Mice ◽  
Skin Wound Healing ◽  
Wound Induction ◽  
Diabetic Wound Healing

AbstractPurposeWe aimed to determine the possible mechanisms of underlying the effects of low dose simvastatin on enhancing the therapeutic efficacy of MSC transplantation in diabetic wound healing.MethodsBalb/c nude mice were divided into five groups:- control mice (CON), diabetic mice (DM), diabetic mice pretreated with low-dose simvastatin (DM+SIM), diabetic mice implanted with MSCs (DM+MSCs) and diabetic mice pretreated with low-dose simvastatin and implanted with MSCs (DM+MSCs+SIM). Seven days before wound induction, low dose simvastatin was orally administered to the DM+SIM and DM+MSCs+SIM groups. Eleven weeks after the induction of diabetes, all mice were given bilateral full-thickness excisional back skin wounds.ResultsBy comparing the DM+MSCs+SIM and DM+MSCs groups, the results showed that on day 14; the wound closure (%WC) and capillary vascularity (%CV) in the DM+MSCs+SIM group were significantly increased compared to those in the DM+MSCs group. In addition, by using immunohistochemical techniques, it was also shown that the expression of SDF-1, a chemotactic factor regulating the migration of stem cells, in the DM+SIM+MSCs group was increased compared with that in the DM+MSCs group. Furthermore, using phospho-Akt (S473) Pan Specific DuoSet IC ELISA (R&D Systems, USA) kits, the increased tissue Akt levels were found in the DM+SIM+MSCs group but not in the other groups.ConclusionsOur study suggests that a low dose of simvastatin enhanced the therapeutic efficacy of MSCs in diabetic wound healing, and this effect was associated with increases in pAkt levels, SDF-1 levels, and angiogenesis, and improved wound closure.

scholarly journals Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix

2021 ◽  
Vol 12 ◽  
pp. 204173142199975
Author(s):  
Jihyun Kim ◽  
Kyoung-Mi Lee ◽  
Seung Hwan Han ◽  
Eun Ae Ko ◽  
Dong Suk Yoon ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Type I ◽  
Diabetic Mice ◽  
Patients With Diabetes ◽  
Diabetic Wound Healing ◽  
Epidermal Growth ◽  
Wound Healing Effect ◽  
Growth Factor Production

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors—stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

scholarly journals A small molecule HIF-1α stabilizer that accelerates diabetic wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Impaired Wound Healing ◽  
Von Hippel Lindau ◽  
Design And Synthesis

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.

scholarly journals Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2554
Author(s):  
Marek Konop ◽  
Anna K. Laskowska ◽  
Mateusz Rybka ◽  
Ewa Kłodzińska ◽  
Dorota Sulejczak ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Diabetic Mice ◽  
Full Thickness ◽  
Skin Wound Healing ◽  
Impaired Wound Healing

Impaired wound healing is a major medical challenge, especially in diabetics. Over the centuries, the main goal of tissue engineering and regenerative medicine has been to invent biomaterials that accelerate the wound healing process. In this context, keratin-derived biomaterial is a promising candidate due to its biocompatibility and biodegradability. In this study, we evaluated an insoluble fraction of keratin containing casomorphin as a wound dressing in a full-thickness surgical skin wound model in mice (n = 20) with iatrogenically induced diabetes. Casomorphin, an opioid peptide with analgesic properties, was incorporated into keratin and shown to be slowly released from the dressing. An in vitro study showed that keratin-casomorphin dressing is biocompatible, non-toxic, and supports cell growth. In vivo experiments demonstrated that keratin-casomorphin dressing significantly (p < 0.05) accelerates the whole process of skin wound healing to the its final stage. Wounds covered with keratin-casomorphin dressing underwent reepithelization faster, ending up with a thicker epidermis than control wounds, as confirmed by histopathological and immunohistochemical examinations. This investigated dressing stimulated macrophages infiltration, which favors tissue remodeling and regeneration, unlike in the control wounds in which neutrophils predominated. Additionally, in dressed wounds, the number of microhemorrhages was significantly decreased (p < 0.05) as compared with control wounds. The dressing was naturally incorporated into regenerating tissue during the wound healing process. Applied keratin dressing favored reconstruction of more regular skin structure and assured better cosmetic outcome in terms of scar formation and appearance. Our results have shown that insoluble keratin wound dressing containing casomorphin supports skin wound healing in diabetic mice.

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