scholarly journals Specific PKC βII inhibitor: one stone two birds in the treatment of diabetic foot ulcers

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Sushant Kumar Das ◽  
Yi Feng Yuan ◽  
Mao Quan Li

To explore whether or not inhibition of protein kinase C βII (PKC βII) stimulates angiogenesis as well as prevents excessive NETosis in diabetics thus accelerating wound healing. Streptozotocin (STZ, 60 mg/kg/day for 5 days, i.p.) was injected to induce type I diabetes in male ICR mice. Mice were treated with ruboxistaurin (30 mg/kg/day, orally) for 14 consecutive days. Wound closure was evaluated by wound area and number of CD31-stained capillaries. Peripheral blood flow cytometry was done to evaluate number of circulating endothelial progenitor cells (EPCs). NETosis assay and wound tissue immunofluorescence imaging were done to evaluate the percentage of neutrophils undergoing NETosis. Furthermore, the expression of PKC βII, protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and histone citrullation (H3Cit) were determined in the wound by Western blot analysis. Ruboxistaurin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in ruboxistaurin-treated diabetic mice. Moreover, ruboxistaurin treatment significantly decreases the percentages of H3Cit+ cells in both peripheral blood and wound areas. This prevented excess activated neutrophils forming an extracellular trap (NETs) formation. The expressions of phospho-Akt (p-Akt), phospho-eNOS (p-eNOS), and VEGF increased significantly in diabetic mice on ruboxistaurin treatment. The expressions of PKC βII and H3Cit+, on the other hand, decreased with ruboxistaurin treatment. The results of the present study suggest that ruboxistaurin by inhibiting PKC βII activation, reverses EPCs dysfunction as well as prevents exaggerated NETs formation in a diabetic mouse model; thereby accelerating the wound healing process.

2021 ◽  
Vol 26 ◽  
pp. 2515690X2098676
Author(s):  
Ana Bertha Hernandez-Hernandez ◽  
Francisco Javier Alarcon-Aguilar ◽  
Mario Garcia-Lorenzana ◽  
Marco Aurelio Rodriguez-Monroy ◽  
Maria Margarita Canales-Martinez

Jatropha neopauciflora is an endemic species of Mexico. Its latex is used to treat wounds, scarring, oral infections, and loose teeth. To date, there are no studies that validate at a morphological level a wound-healing use in diabetes. The present research aimed to evaluate the wound-healing capacity of the latex of J. neopauciflora in the skin of healthy and streptozotocin-induced diabetic mice. Also, a chemical analysis of the latex through molecular exclusion chromatography and HPLC were performed. Male mice ( Mus musculus) of 7-week-old CD1 strain were used. Groups of healthy and diabetic mice were formed. A longitudinal cut of 1 cm was performed on the depilated skin. All treatments were topically applied to the wound area twice a day for ten days. At the end of the experiments, the skin sections were obtained from the wound area and stained with Hematoxylin-Eosin. Then we counted the number of active fibroblasts in all the experimental groups. In normal mice, the latex accelerated the wound-healing process and decreased the number of active fibroblasts, similarly to Recoveron. In diabetic mice, the latex and Recoveron increased the number of active fibroblasts. In normal and diabetic mice, a thin and orderly epidermis was observed. Molecular exclusion chromatography exhibited 58 fractions, 14 of which were subjected to HPLC, to detect catechin, a flavonoid with antioxidant, antimicrobial, and anti-inflammatory properties. J. neopauciflora latex can be useful for wound treatment in patients with diabetes mellitus because it accelerates and promotes the wound-healing process.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2554
Author(s):  
Marek Konop ◽  
Anna K. Laskowska ◽  
Mateusz Rybka ◽  
Ewa Kłodzińska ◽  
Dorota Sulejczak ◽  
...  

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.


2019 ◽  
Vol 34 (8) ◽  
pp. 1171-1187
Author(s):  
Farnoush Oveissi ◽  
Naser Tavakoli ◽  
Mohsen Minaiyan ◽  
Mohammad Reza Mofid ◽  
Azade Taheri

Epidermal lipoxygenase enzyme extracted from Ambystoma mexicanum (AmbLOXe) is known to accelerate the wound-healing process. AmbLOXe as a protein suffers from inactivation and losing its activity during formulation. Therefore, a delivery system that protects AmbLOXe from inactivation and preserves its activity is needed. We prepared AmbLOXe-loaded pectin nanoparticles (AmbLOXe Pec-NPs) and placed them into an alginate hydrogel. AmbLOXe Pec-NPs incorporation into the alginate hydrogel provides a means for controlled and sustained delivery of AmbLOXe to the wound site. Furthermore, the suitable swelling behavior and mechanical properties of AmbLOXe Pec-NPs alginate hydrogel make it feasible for clinical use. AmbLOXe Pec-NPs alginate hydrogel significantly enhanced the wound-healing process on the rat full-thickness excisional wounds, increased the rate of wound closure, enhanced the re-epithelialization and decreased the incidence of abnormal scarring. AmbLOXe Pec-NPs alginate hydrogel can be proposed as an effective wound hydrogel for improving wound healing with minimal scarring.


2019 ◽  
Vol 81 (4) ◽  
Author(s):  
Ulfah Anwar ◽  
Siti Pauliena Mohd Bohari

The aim of this research is to investigate the wound healing process in in vitro by combining the Manihot esculenta aqueous extract and therapeutic ultrasound. Firstly, the optimization seeding densities of HSF cell 1184 in six-well plate, and then followed by the scratch assay experiment. The scratched that made was treated with the remedial treatments (Manihot esculenta aqueous extract only; ascorbic acid+ therapeutic ultrasound; Manihot esculenta aqueous extract+ ascorbic acid; Manihot esculenta aqueous extract+ therapeutic ultrasound and also the combination of these three materials). The rate of wound closure was observed and analysed at a time interval of 0, 2, 4, 6, 8, 10 and 24 h by using image J software. Then, the cells viability were analysed using the MTT assay. The result showed that Manihot esculenta aqueous extract coupled with specific dose therapeutic ultrasound represents a significantly high rate of wound closure at 96.10 % with the cell numbers at 5.44×105 cells/mL when compared to the other combination therapy. The finding of this study revealed that Manihot esculenta aqueous extract 200 µg/mL and the therapeutic ultrasound specific dose (3 MHz, 300 mWatt/cm2, 50% in 5 min) have the potential in accelerating wound healing process of cells in in vitro.


2019 ◽  
Vol 10 ◽  
Author(s):  
Sandra Helena Penha Oliveira ◽  
Victor Gustavo Balera Brito ◽  
Sabrina Cruz Tfaile Frasnelli ◽  
Bianca da Silva Ribeiro ◽  
Milena Nunes Ferreira ◽  
...  

2020 ◽  
Vol 45 (6) ◽  
Author(s):  
I. A. Ajayi ◽  
O. B. Omolere

This study investigated the wound healing potential of hexane and methanolic seed extracts of Azadirachta indica using 35 wistar rats that were divided into 5 groups of 7 rats each. Phytochemical screening and antimicrobial activity of the extracts were carried out while the wound healing potential was evaluated by treating the test rats with 5 % and 10 % hexane and methanol extracts in an experiment that lasted for 21 days. Wound area and percentage of wound closure of the rats were noted at four-day intervals and at 21 days, the blood and organs of the rats were subjected to haematological and histopathological analyses respectively. The extracts were found to contain tannins, glycosides and phenols and they inhibited the growth of tested organisms. All the test rats displayed better and faster healing than the control ones but there were no significant differences between their haematological and histophatological results. The seed extracts quickened the wound healing process of the rats and might therefore be useful in wound treatment.


2020 ◽  
Vol 5 (01) ◽  
pp. 1-10
Author(s):  
Risa Umami ◽  
Riwayati Malika

Diabetes mellitus (DM) is characterized by an increase in glucose levels in the blood due to disorders of glucose metabolism in the body. The pancreas organ of people with DM has a weakness in producing the hormone insulin. As a result, the distribution of blood glucose to other organs of the body is inhibited so that glucose levels in the blood increase which causes DM sufferers to experience longer wound healing than normal humans. Binahong leaves contain alkaloids, saponins and flavonoids which have antibacterial activity which can accelerate the wound healing process. The purpose of this study was to determine the antibacterial effect of binahong leaf extract ointment (Anredera cordifolia) against Staphylococcus aureus bacteria from diabetic wounds. This research includes antibacterial test for binahong leaf extract ointment (Anredera cordifolia) with variations in the concentration of 10%, 20%, and 30% of the concentration of binahong leaf extract of 25% which resulted in a wound coverage percentage of up to 100%, namely at 30% ointment concentration. The conclusion of this study is that there was no wound closure for negative control and positive control in the form of oxytetracycline, the percentage of wound closure was 85%.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir

Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.


2000 ◽  
Vol 278 (1) ◽  
pp. L13-L18 ◽  
Author(s):  
Hiroyuki Miki ◽  
Tadashi Mio ◽  
Sonoko Nagai ◽  
Yuma Hoshino ◽  
Takeo Tsutsumi ◽  
...  

Fibroblast contractility plays a useful role in the wound healing process but contributes to architectural distortion in the lungs. Glucocorticoids (GCs) have been reported to reduce dermal fibroblast contractility, which may result in delaying wound healing, but the effects on lung fibroblasts are unknown. In this study, we examined how human lung fibroblast contractility is altered in the presence of GCs. Lung fibroblast cell lines ( n = 5) were established from normal parts of surgically resected lung tissue. The effects of GCs on contractility were investigated with a type I collagen gel contraction assay. Filamentous actin (F-actin) content was detected by confocal microscopy and measured with a fluorescent phalloidin binding assay. GCs augmented fibroblast contraction in a concentration-dependent manner, with an approximate EC50 of 1.8 × 10−8 M, whereas other steroid derivatives had no effects. GC contractility needed de novo protein synthesis. The GC-induced increase in contractility was found to be consistent with an increase in F-actin content. In conclusion, lung fibroblast contractility was enhanced with GCs through an upregulation of lung fibroblast F-actin.


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