Improved stability of KGF by conjugation with gold nanoparticles for diabetic wound therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (22) ◽  
pp. 2909-2923 ◽  
Author(s):  
Shuaihua Li ◽  
Qiyu Tang ◽  
Hongbo Xu ◽  
Qiangru Huang ◽  
Zi Wen ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Wound Healing ◽  
Binding Affinity ◽  
Biological Effects ◽  
Diabetic Rats ◽  
Diabetic Wound ◽  
Wound Therapy ◽  
Improved Stability ◽  
Diabetic Wound Healing

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.

scholarly journals Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function

2020 ◽  
Vol 8 ◽  
Author(s):  
Pei Wei ◽  
Chenjian Zhong ◽  
Xiaolan Yang ◽  
Futing Shu ◽  
Shichu Xiao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Biological Effects ◽  
Mtor Pathway ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Human Amniotic Epithelial Cells

Abstract Background Diabetic wounds are one of the most common and serious complications of diabetes mellitus, characterized by the dysfunction of wound-healing-related cells in quantity and quality. Our previous studies revealed that human amniotic epithelial cells (hAECs) could promote diabetic wound healing by paracrine action. Interestingly, numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy. However, whether exosomes derived from hAECs (hAECs-Exos) mediate the effects of hAECs on diabetic wound healing remains unclear. This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism. Methods hAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy, dynamic light scattering and flow cytometry. A series of in vitro functional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts (HFBs) and human umbilical vein endothelial cells (HUVECs) in a high-glycemic microenvironment. High-throughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs. Subsequently, the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs, as well as in diabetic wound healing, was assessed. Results hAECs-Exos presented a cup- or sphere-shaped morphology with a mean diameter of 105.89 ± 10.36 nm, were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs. After that, hAECs-Exos not only significantly promoted the proliferation and migration of HFBs, but also facilitated the angiogenic activity of HUVECs in vitro. High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway. Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs, as well as on wound healing, in diabetic mice. Conclusions Our findings demonstrated that hAECs-Exos represent a promising, novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway.

Therapeutic Properties of Honey for the Management of Wounds; Is There a Role in the Armamentarium of Diabetic Foot Ulcer Treatment? Results From In vitro and In vivo Studies

2021 ◽  
pp. 153473462110268
Author(s):  
Ioanna A. Anastasiou ◽  
Ioanna Eleftheriadou ◽  
Anastasios Tentolouris ◽  
Georgia Samakidou ◽  
Nikolaos Papanas ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Diabetic Animal ◽  
Cochrane Library ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Therapeutic Properties

Diabetic foot ulcers are one of the most dreadful complications of diabetes mellitus and efforts to accelerate diabetic wound healing are of paramount importance to prevent ulcer infections and subsequent lower-limb amputations. There are several treatment approaches for the management of diabetic foot ulcers and honey seems to be a safe and cost-effective therapeutic approach on top of standard of care. The aim of this review was to summarize the therapeutic properties of honey and the data regarding its possible favorable effects on diabetic wound healing. A literature search of articles from 1986 until April 2021 was performed using MEDLINE, EMBASE, and the Cochrane Library to assess for studies examining the therapeutic wound healing properties of honey, it's in vitro effect, and the efficacy and/or mechanism of action of several types of honey used for the treatment of diabetic animal wounds. Honey has antioxidant, anti-inflammatory, and antibacterial properties and in vitro studies of keratinocytes and fibroblasts, as well as studies in diabetic animal models show that treatment with honey is associated with increased re-epithelialization and collagen production, higher wound contraction, and faster wound healing. The use of honey could be a promising approach for the management of diabetic foot ulcers.

Extracellular vesicles derived from adipose-derived stem cells accelerate diabetic wound healing by suppressing the expression of matrix metalloproteinase-9

2021 ◽  
Vol 22 ◽  
Author(s):  
Jiang-wen Wang ◽  
Yuan-zheng Zhu ◽  
Xuan Hu ◽  
Jia-ying Nie ◽  
Zhao-hui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mouse Model ◽  
Adipose Derived Stem Cells ◽  
Collagen Deposition ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds ◽  
Metalloproteinase 9

Background: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. Objective: In this study, we explored if ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. Methods: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA), using CCK-8 western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effect of ADSC-EVs on the healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids was evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson’s trichrome, and immunofluorescence staining for MMP-9. Results: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells.In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. Conclusion: ADSC-EVs possessed the healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition.Thus ,ADSC-EVs are a promising candidate for the treatment of diabetic wounds .

scholarly journals Identification of Structurally Similar Phytochemicals to Quercetin with High SIRT1 Binding Affinity and Improving Diabetic Wound Healing by Using In silico Approaches

2021 ◽  
Vol 12 (6) ◽  
pp. 7621-7632
Keyword(s):  
Wound Healing ◽  
In Silico ◽  
Binding Free Energy ◽  
Biological Properties ◽  
In Vivo Studies ◽  
Diabetic Wound ◽  
Binding Modes ◽  
Diabetic Wound Healing

Diabetes Mellitus is the most prevalent metabolic disorder that is increasing at an alarming rate worldwide. The unregulated glucose level leads to various types of health disorders, and one of the major diabetic complications is delayed wound healing. Due to the more side effects of synthetic drugs, there is a need to explore plants and their phytochemicals for medicinal purposes. It was found that Quercetin, a flavonoid, increases the rate of diabetic wound healing by enhancing the expression of SIRT1. This demands more insight towards Quercetin and its similar compounds, as it is hypothesized that similar compounds may have similar biological properties. Thus similarity searching was done to identify the most similar compounds of Quercetin, and then the molecular docking of the screened compounds was performed using AutoDock Vina. The unique ligands were docked into the active site of SIRT1 protein (PDB ID: 4ZZJ). The binding free energy of the interacting ligand with the protein was estimated. Six compounds were identified which possess the maximum structural similarity with Quercetin, and upon docking, it was found that gossypetin and herbacetin have similar binding modes and binding energy as that of Quercetin (-7.5 kcal/mol). Therefore, the hypothesis has been validated by in silico analysis. Our study identified two phytochemicals, Gossypetin, and Herbacetin which can prove beneficial for improving diabetic wound healing but needs to be validated further by in vitro and in vivo studies.

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.

Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats

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

scholarly journals KLF4 Promotes Diabetic Chronic Wound Healing by Suppressing Th17 Cell Differentiation in an MDSC-Dependent Manner

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xiong Yang ◽  
Bryan J. Mathis ◽  
Yu Huang ◽  
Wencheng Li ◽  
Ying Shi
Keyword(s):  
Wound Healing ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Chronic Wound ◽  
Suppressor Cells ◽  
Dependent Manner ◽  
Diabetic Wound ◽  
Diabetic Wound Healing ◽  
Th17 Differentiation

Objectives. Diabetic wound inflammation deficiencies lead to ulcer development and eventual amputation and disability. Our previous research demonstrates that myeloid-derived suppressor cells (MDSCs) accumulate during inflammation and promote chronic wound healing via the regulation of Kruppel-like factor 4 (KLF4). In this study, we aimed to investigate the potential roles of MDSCs and KLF4 in diabetic wound healing. Methods. An ob/ob mouse pressure ulcer (PU) model was used to evaluate the process of wound healing. The expression levels of KLF4 and IL-17A were measured by real-time PCR, and the population of MDSCs and Th17 cells was measured by flow cytometry. The levels of cytokines were determined by an immunosuppression assay. Results. KLF4 deficiency in the diabetic PU model resulted in decreased accumulation of MDSCs, increased expansion of Th17 cells, and significantly delayed wound healing. Conversely, KLF4 activation by APTO-253 accelerated wound healing accompanied by increased MDSC populations and decreased numbers of Th17 cells. MDSCs have been proven to mediate Th17 differentiation via cytokines, and our in vitro data showed that elevated KLF4 expression in MDSCs resulted in reduced Th17 cell numbers and, thus, decreased levels of cytokines indispensable for Th17 differentiation. Conclusions. Our study revealed a previously unreported function of KLF4-regulated MDSCs in diabetic wound healing and identified APTO-253 as a potential agent to improve the healing of pressure ulcers.

scholarly journals Huangbai Liniment Accelerated Wound Healing by Activating Nrf2 Signaling in Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Jingjing Zhang ◽  
Rui Zhou ◽  
Changpei Xiang ◽  
Qiang Jia ◽  
Hongwei Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oxidative Damage ◽  
Drug Targets ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Diabetic Wound ◽  
Antioxidant Genes ◽  
Thioredoxin System ◽  
Forsythia Suspensa

As a serious complication of diabetes, nonhealing skin ulcer leads to high mortality and disability in diabetic patients. However, limited therapy is available in managing diabetic wounds. In this study, RNA-seq technology was used to systematically investigate the effect of Huangbai (HB) liniment, a traditional Chinese medicine, on the streptozotocin- (STZ-) induced diabetic wound. HB liniment significantly accelerated the wound closure and enhanced the generation of extracellular matrix in diabetic rats, and oxidative stress was identified to play a vital role in HB-mediated wound healing. Importantly, HB liniment activated nuclear factor erythroid-derived 2-like 2 (Nrf2) and its downstream antioxidant genes (e.g., genes involved in glutathione system, thioredoxin system, and GAPDH generation as well as other antioxidant genes), which inhibited oxidative damage and apoptosis. By associating drug targets of HB liniment with Nrf2 and its downstream genes, 54 components in HB liniment were screened out, and the majority was from Cortex Phellodendri and Forsythia suspensa. Additionally, HB liniment enhanced TGF-β1 and reduced MMP9 level, accelerating wound healing in diabetes. The in vitro experiment showed HB facilitated cell proliferation and inhibited oxidative damage in high glucose-induced HaCaT cells. Our findings provided the experimental evidence for the treatment of diabetic wound with HB, clarified the potential mechanism of HB, and improved our understanding of diabetic wound healing.

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