scholarly journals Topical Application of Propolis Enhances Cutaneous Wound Healing by Promoting TGF-Beta/Smad-Mediated Collagen Production in a Streptozotocin-Induced Type I Diabetic Mouse Model

2015 ◽  
Vol 37 (3) ◽  
pp. 940-954 ◽  
Author(s):  
Wael N. Hozzein ◽  
Gamal Badr ◽  
Ahmad A. Al Ghamdi ◽  
Ayat Sayed ◽  
Noori S. Al-Waili ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mouse Model ◽  
Topical Application ◽  
Marked Reduction ◽  
Diabetic Mouse ◽  
Type I ◽  
Diabetic Mice ◽  
Tnf Α ◽  
Diabetic Wounds ◽  
Tgf Β1

Background/Aims: Impaired wound healing is considered to be one of the most serious complications associated with diabetes as it significantly increases the susceptibility of patients to infection. Propolis is a natural bee product used extensively in foods and beverages that has significant benefits to human health. In particular, propolis has antioxidant, anti-inflammatory and analgesic effects that could be useful for improving wound healing. In this study, we investigated the effects of topical application of propolis on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model. Methods: Sixty male mice were distributed equally into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated daily with a topical application of propolis. Results: We found that diabetic mice exhibited delayed wound closure characterized by a significant decrease in the levels of TGF-β1 and a prolonged elevation of the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and MMP9 in wound tissues compared with control non-diabetic mice. Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad2 and Smad3 as well as a marked reduction in collagen production. Interestingly, compared with untreated diabetic mice, topical application of propolis significantly enhanced the closure of diabetic wounds and decreased the levels of IL-1β, IL-6, TNF-α and MMP9 to near normal levels. Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-β1/Smad2,3 signaling axis in wounded tissues. Conclusion: Our findings reveal the molecular mechanisms underlying the improved healing and closure of diabetic wounds following topical propolis application.

scholarly journals Topical treatment of ointment containing ethanol extract of Archidendron pauciflorum fruit peel on the wound healing in streptozotocin-induced diabetic mice

2017 ◽  
Vol 9 (3) ◽  
pp. 306-311 ◽  
Author(s):  
DESAK MADE MALINI ◽  
MADIHAH MADIHAH ◽  
FITRI KAMILAWATI ◽  
NINING RATNINGSIH ◽  
KARTIAWATI ALIPIN ◽  
...  
Keyword(s):  
Wound Healing ◽  
Topical Application ◽  
Topical Treatment ◽  
Healing Process ◽  
Ethanol Extract ◽  
Negative Control ◽  
Control Group ◽  
Diabetic Mice ◽  
Fruit Peel ◽  
Diabetic Wounds

Malini DM, Madihah, Kamilawati F, Ratningsih N, Alipin K, Iskandar J. 2017. Topical treatment of ointment containing ethanol extract of Archidendron pauciflorum fruit peel on the wound healing in streptozotocin-induced diabetic mice. Nusantara Bioscience 9: 306-311. Diabetic wounds lead to severe tissue damage and are difficult to cure. One alternative medicine known well by local Indonesian communities to treat diabetic wounds is the fruit peel of djengkol. This study aimed to evaluate the ointment containing ethanol extract of djengkol fruit peel to accelerate wound healing process in the skin of streptozotocin-induced diabetic mice. The method was experimental using completely randomized design with six treatments and four replications. Diabetes was induced by intraperitoneal injection of streptozotocin 180 mg/kg BW. Mice with blood glucose level ≥150 mg/dL were used for diabetic mice models. The incision wound created at dorsolateral region of shaven skin at ±1 cm2 using sterile scissors. The ointment containing extract was applied topically to the diabetic mice wounds at concentration of 5%, 10% and 15%, as well as Betadine® as the reference group. The ointment basis was applied to the wound of diabetic mice as a positive control and to the wound of non-diabetic mice as a negative control. The treatment was done twice a day for 14 days. The results showed that topical application of ointment containing ethanol extract of djengkol fruit peel at concentration of 10% gave significant recovery (p<0.05) on the wounded skin by the enhancement of re-epithelization and granulation tissue, as well as the increase of capillary number and collagen density which were higher than other treatments and comparable to negative control group. It was concluded that the topical application of ointment containing ethanol extract of djengkol fruit peel can support the healing of diabetic wounds.

scholarly journals Sodium Butyrate Plus EGF and PDGF-BB Aids Cutaneous Wound Healing in Diabetic Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Rohini Keshava ◽  
Rajalakshmi Gope
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Topical Application ◽  
Sodium Butyrate ◽  
Diabetic Patients ◽  
Cutaneous Wound Healing ◽  
Diabetic Mice ◽  
Tissue Samples ◽  
Cutaneous Wound ◽  
Diabetic Wounds

Topical application of growth factors is known to aid defective and/or delayed wound healing in diabetic patients. In this study, the effect of topical application of sodium butyrate (Na-Bu), EGF, and PDGF-BB was analysed on the acute cutaneous wound healing in streptozotocin (STZ) induced diabetic mouse model. Two cutaneous wounds were created, one on each of the dorsolateral sides of the diabetic mice. Na-Bu, EGF, and PDGF-BB were applied to the wound either individually or in various combinations. The wound healing was monitored visually and scored as percentage wound closure. The tissue samples were collected from the wound site at 1, 7, and 14 days after wounding from the treated and untreated diabetic wounds and analysed for the levels of EGF-R, β-PDGF-R, HDAC1, p21, and phosphorylated and hypophosphorylated pRb proteins. Our results indicate that application of EGF plus PDGF-BB at the initial stages followed by subsequent addition of Na-Bu along with these growth factors helps wound healing in diabetic mice. It appears that, in addition to cell proliferative agents, a cell differentiation agent, Na-Bu, is necessary for diabetic wound healing. Topical application of EGF plus PDGF-BB along with Na-Bu could be developed as therapeutic agents to treat and manage human diabetic wounds.

scholarly journals Topical Application of Adelmidrol + Trans-Traumatic Acid Enhances Skin Wound Healing in a Streptozotocin-Induced Diabetic Mouse Model

2018 ◽  
Vol 9 ◽  
Author(s):  
Rosalba Siracusa ◽  
Daniela Impellizzeri ◽  
Marika Cordaro ◽  
Enrico Gugliandolo ◽  
Alessio F. Peritore ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mouse Model ◽  
Topical Application ◽  
Diabetic Mouse ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Traumatic Acid

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.

A mitochondria-targeted near-infrared fluorescent probe for imaging viscosity in living cells and a diabetic mice model

2021 ◽  
Author(s):  
Bochao Chen ◽  
Shumei Mao ◽  
Yanyan Sun ◽  
Liyuan Sun ◽  
Ning Ding ◽  
...  
Keyword(s):  
Mouse Model ◽  
Fluorescent Probe ◽  
Near Infrared ◽  
Diabetic Mouse ◽  
Living Cells ◽  
Pancreatic Tissue ◽  
Diabetic Mice ◽  
Mice Model ◽  
Viscosity Changes

A mitochondria-targeted near-infrared fluorescent probe NIR-V with 700 nm emission was designed to monitor cell viscosity changes, which was applied to detect the intracellular viscosity and imagine pancreatic tissue in diabetic mouse model.

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 .

Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy

2018 ◽  
Vol 52 (4) ◽  
pp. 373-383 ◽  
Author(s):  
Sisse A Nørgaard ◽  
Fredrik W Sand ◽  
Dorte B Sørensen ◽  
Klas SP Abelson ◽  
Henrik Søndergaard
Keyword(s):  
Weight Loss ◽  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Diabetic Mouse ◽  
Diabetic Mice ◽  
Reduce Weight Loss ◽  
Normal Chow ◽  
Corticosterone Metabolites ◽  
Reducing Stress ◽  
Humane Endpoint

The streptozotocin (STZ)-induced diabetic mouse is a widely used model of diabetes and diabetic nephropathy (DN). However, it is a well-known issue that this model is challenged by high weight loss, which despite supportive measures often results in high euthanization rates. To overcome these issues, we hypothesized that supplementing STZ-induced diabetic mice with water-softened chow in addition to normal chow would reduce weight loss, lower the need for supportive treatment, and reduce the number of mice reaching the humane endpoint of 20% weight loss. In a 15 week STZ-induced DN study we demonstrated that diabetic male mice receiving softened chow had reduced acute weight loss following STZ treatment ( p = 0.045) and additionally fewer mice were euthanized due to weight loss. By supplementing the diabetic mice with softened chow, no mice reached 20% weight loss whereas 37.5% of the mice without this supplement reached this humane endpoint ( p = 0.0027). Excretion of corticosterone metabolites in faeces was reduced in diabetic mice on softened chow ( p = 0.0007), suggesting lower levels of general stress. Finally, it was demonstrated that the water-softened chow supplement did not significantly affect the induction of key disease parameters, i.e. %HbA1C and albuminuria nor result in abnormal teeth wear. In conclusion, supplementation of softened food is refining the STZ-induced diabetic mouse model significantly by reducing stress, weight loss and the number of animals sacrificed due to humane endpoints, while maintaining the key phenotypes of diabetes and nephropathy.

scholarly journals Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew P. Sawaya ◽  
Rivka C. Stone ◽  
Stephen R. Brooks ◽  
Irena Pastar ◽  
Ivan Jozic ◽  
...  
Keyword(s):  
Wound Healing ◽  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Diabetic Mouse ◽  
Transcriptional Networks ◽  
Life Threatening ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Abstract Diabetic foot ulcers (DFUs) are a life-threatening disease that often result in lower limb amputations and a shortened lifespan. However, molecular mechanisms contributing to the pathogenesis of DFUs remain poorly understood. We use next-generation sequencing to generate a human dataset of pathogenic DFUs to compare to transcriptional profiles of human skin and oral acute wounds, oral as a model of “ideal” adult tissue repair due to accelerated closure without scarring. Here we identify major transcriptional networks deregulated in DFUs that result in decreased neutrophils and macrophages recruitment and overall poorly controlled inflammatory response. Transcription factors FOXM1 and STAT3, which function to activate and promote survival of immune cells, are inhibited in DFUs. Moreover, inhibition of FOXM1 in diabetic mouse models (STZ-induced and db/db) results in delayed wound healing and decreased neutrophil and macrophage recruitment in diabetic wounds in vivo. Our data underscore the role of a perturbed, ineffective inflammatory response as a major contributor to the pathogenesis of DFUs, which is facilitated by FOXM1-mediated deregulation of recruitment of neutrophils and macrophages, revealing a potential therapeutic strategy.

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