scholarly journals Exosomal Vimentin from Adipocyte Progenitors Protects Fibroblasts against Osmotic Stress and Inhibits Apoptosis to Enhance Wound Healing

2021 ◽  
Vol 22 (9) ◽  
pp. 4678
Author(s):  
Sepideh Parvanian ◽  
Hualian Zha ◽  
Dandan Su ◽  
Lifang Xi ◽  
Yaming Jiu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Osmotic Stress ◽  
Mechanical Stress ◽  
Impaired Wound Healing ◽  
In Vivo Experiments ◽  
Adipocyte Progenitors ◽  
Osmotic Balance ◽  
Induced Apoptosis

Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts’ response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions.

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 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 Overview of Cold Atmospheric Plasma in Wounds Treatment

2020 ◽  
Vol 5 (10) ◽  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Atmospheric Plasma ◽  
Active Components ◽  
Negative Effects ◽  
Skin Wound Healing ◽  
Cold Atmospheric Plasma ◽  
In Vivo Experiments

Cold atmospheric plasma (CAP), a room temperate ionised gas, known as the fourth state of matter is an ionised gas and can be produced from argon, helium, nitrogen, oxygen or air at atmospheric pressure and low temperatures. CAP has become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing have gained huge success both in vitro and in vivo experiments without any known significant negative effects on healthy tissues. The development of CAP devices has led to novel therapeutic strategies in wound healing, tissue regeneration and skin infection management. CAP consists of a mixture of multitude of active components such as charged particles, electric field, UV radiation, and reactive gas species which can act synergistically. CAP has lately been recognized as an alternative approach in medicine for sterilization of wounds by its antiseptic effects and promotion of wound healing by stimulation of cell proliferation and migration of wound related skin cells. With respect to CAP applications in medicine, this review focuses particularly on the potential of CAP and the known molecular basis for this action. We summarize the available literature on the plasma devices developed for wound healing, the current in vivo and in vitro use of CAP, and the mechanism behind it as well as the biosafety issues.

scholarly journals Patterned Polyvinyl Alcohol Hydrogel Dressings with Stem Cells Seeded for Wound Healing

Polymers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 171 ◽  
Author(s):  
Tianlin Gao ◽  
Menghui Jiang ◽  
Xiaoqian Liu ◽  
Guoju You ◽  
Wenyu Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Polyvinyl Alcohol ◽  
Adipose Derived Stem Cells ◽  
In Vivo Experiments ◽  
Cell Counts ◽  
Surface Modified ◽  
Testing Instruments

Polyvinyl alcohol (PVA) hydrogel and stem cell therapy have been widely used in wound healing. However, the lack of bioactivity for PVA and security of stem therapy limited their application. In this study, an adipose-derived stem cells (ADSCs)-seeded PVA dressing (ADSCs/PVA) was prepared for wound healing. One side of the PVA dressing was modified with photo-reactive gelatin (Az-Gel) via ultraviolet (UV) irradiation (Az-Gel@PVA), and thus ADSCs could adhere, proliferate on the PVA dressings and keep the other side of the dressings without adhering to the wound. The structure and mechanics of Az-Gel@PVA were determined by scanning electron microscopy (SEM) and material testing instruments. Then, the adhesion and proliferation of ADSCs were observed via cell counts and live-dead staining. Finally, in vitro and in vivo experiments were utilized to confirm the effect of ADSCs/PVA dressing for wound healing. The results showed that Az-Gel was immobilized on the PVA and showed little effect on the mechanical properties of PVA hydrogels. The surface-modified PVA could facilitate ADSCs adhesion and proliferation. Protein released tests indicated that the bioactive factors secreted from ADSCs could penetrated to the wound. Finally, in vitro and in vivo experiments both suggested the ADSCs/PVA could promote the wound healing via secreting bioactive factors from ADSCs. It was speculated that the ADSCs/PVA dressing could not only promote the wound healing, but also provide a new way for the safe application of stem cells, which would be of great potential for skin tissue engineering.

Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes

2013 ◽  
Vol 305 (8) ◽  
pp. E951-E963 ◽  
Author(s):  
Milad S. Bitar ◽  
Samy M. Abdel-Halim ◽  
Fahd Al-Mulla
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Cellular Senescence ◽  
Dermal Fibroblasts ◽  
Premature Senescence ◽  
Mrna Levels ◽  
Impaired Wound Healing ◽  
Caveolin 1

A heightened state of oxidative stress and senescence of fibroblasts constitute potential therapeutic targets in nonhealing diabetic wounds. Here, we studied the underlying mechanism mediating diabetes-induced cellular senescence using in vitro cultured dermal fibroblasts and in vivo circular wounds. Our results demonstrated that the total antioxidant capacity and mRNA levels of thioredoxinreductase and glucose-6-phosphate dehydrogenase as well as the ratio of NADPH/NADP were decreased markedly in fibroblasts from patients with type 2 diabetes (DFs). Consistent with this shift in favor of excessive reactive oxygen species, DFs also displayed a significant increase in senescence-associated β-galactosidase activity and phospho-γ-histone H2AX (pH2AX) level. Moreover, the ability of PDGF to promote cell proliferation/migration and regulate the phosphorylation-dependent activation of Akt and ERK1/2 appears to be attenuated as a function of diabetes. Mechanistically, we found that diabetes-induced oxidative stress upregulated caveolin-1 (Cav-1) and PTRF expression, which in turn sequestered Mdm2 away from p53. This process resulted in the activation of a p53/p21-dependent pathway and the induction of premature senescence in DFs. Most of the aforementioned oxidative stress and senescence-based features observed in DFs were recapitulated in a 10-day-old diabetic wound. Intriguingly, we confirmed that the targeted depletion of Cav-1 or PTRF using siRNA- or Vivo-Morpholino antisense-based gene therapy markedly inhibited diabetes/oxidative stress-induced premature senescence and also accelerated tissue repair in this disease state. Overall, our data illuminate Cav-1/PTRF-1 as a key player of a novel signaling pathway that may link a heightened state of oxidative stress to cellular senescence and impaired wound healing in diabetes.

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 Puerarin Improves Dexamethasone-Impaired Wound Healing In Vitro and In Vivo by Enhancing Keratinocyte Proliferation and Migration

2021 ◽  
Vol 11 (19) ◽  
pp. 9343
Author(s):  
Ly Thi Huong Nguyen ◽  
Sang-Hyun Ahn ◽  
Min-Jin Choi ◽  
In-Jun Yang ◽  
Heung-Mook Shin
Keyword(s):  
Wound Healing ◽  
Healing Process ◽  
Wound Healing Process ◽  
Hacat Cells ◽  
Impaired Wound Healing ◽  
Keratinocyte Proliferation ◽  
And Migration ◽  
Proliferation And Migration

The delayed and impaired wound healing caused by dexamethasone (DEX) is commonly reported. Puerarin, the major isoflavone found in Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep promoted the wound healing process in diabetic rats. However, the effects and underlying mechanisms of puerarin on DEX-impaired wound healing have not been investigated. This study examined the potential uses of puerarin in upregulating keratinocyte proliferation and migration in dexamethasone (DEX)-suppressed wound healing model. The effects of puerarin on wound healing in vivo were investigated by taking full-thickness 5 mm punch biopsies from the dorsal skin of BALB/c mice and then treating them topically with 0.1% DEX. For the in vitro study, DEX-treated HaCaT cells were used to examine the effects of puerarin on DEX-induced keratinocyte proliferation and migration and the mechanisms of its action. Puerarin, when applied topically, accelerated the wound closure rate, increased the density of the capillaries, and upregulated the level of collagen fibers and TGF-β in the wound sites compared to the DEX-treated mice. Puerarin promoted the proliferation and migration of keratinocytes by activating the ERK and Akt signaling pathways in DEX-treated HaCaT cells. In conclusion, puerarin could be effective in reversing delayed and disrupted wound healing associated with DEX treatments.

Development of a novel keratin dressing which accelerates full-thickness skin wound healing in diabetic mice: In vitro and in vivo studies

2018 ◽  
Vol 33 (4) ◽  
pp. 527-540 ◽  
Author(s):  
Marek Konop ◽  
Joanna Czuwara ◽  
Ewa Kłodzińska ◽  
Anna K Laskowska ◽  
Urszula Zielenkiewicz ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Healing Process ◽  
Skin Wound ◽  
In Vivo Studies ◽  
Histopathological Analysis ◽  
Full Thickness ◽  
Impaired Wound Healing

Impaired wound healing is a major medical problem in diabetes. The objective of this study was to determine the possible application of an insoluble fraction of fur-derived keratin biomaterial as a wound dressing in a full thickness surgical skin wound model in mice ( n = 20) with iatrogenically induced diabetes. The obtained keratin dressing was examined in vitro and in vivo. In vitro study showed the keratin dressing is tissue biocompatible and non-toxic for murine fibroblasts. Antimicrobial examination revealed the keratin dressing inhibited the growth of S. aureus and E. coli. In vivo studies showed the obtained dressing significantly ( p < 0.05) accelerated healing during the first week after surgery compared to control wounds. Keratin dressings were incorporated naturally into granulation and regenerating tissue without any visible signs of inflammatory response, which was confirmed by clinical and histopathological analysis. It is one of the first studies to show application of insoluble keratin proteins and its properties as a wound dressing. The obtained keratin dressing accelerated wound healing in mice with iatrogenically induced diabetes. Therefore, it can be considered as a safe and efficient wound dressing. Although future studies are needed to explain the molecular mechanism behind fur-derived keratin effect during the multilayer wound healing process, our findings may open the way for a new class of insoluble fur keratin dressings in chronic difficult to heal wounds treatment.

scholarly journals GW4064 Enhances the Chemosensitivity of Colorectal Cancer to Oxaliplatin by Inducing Pyroptosis

2020 ◽  
Author(s):  
Jing Guo ◽  
Jianbao Zheng ◽  
Zhengshui Xu ◽  
Chenye Zhao ◽  
Kui Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Farnesoid X Receptor ◽  
Antitumor Effects ◽  
In Vivo Experiments ◽  
Stat3 Signaling ◽  
Synergistic Mechanism ◽  
Combination Study ◽  
Induced Apoptosis

Abstract Background Repeated and long-term oxaliplatin therapy leads to drug resistance and severe adverse events, which limit its clinical use. These difficulties highlight the importance of identifying potent and specific drug combinations to enhance the antitumor effects of oxaliplatin. The farnesoid X receptor (FXR) deficiency in colorectal cancer (CRC) suggests that restoring FXR function might be a promising strategy for CRC treatment.Methods A series of in vitro and in vivo experiments were conducted to assess the antitumor effect of the combination of oxaliplatin and FXR agonist GW4064 in CRC. The synergistic mechanism involved was explored.Results A drug combination study showed that the GW4064 acted synergistically with oxaliplatin in colon cancer cells. The combination of oxaliplatin plus GW4064 inhibited cell growth and colony formation, induced apoptosis and pyroptosis in vitro, and slowed tumor growth in vivo. Mechanistically, GW4064 enhanced the chemosensitivity of cells to oxaliplatin by inducing BAX/caspase-3/GSDME-mediated pyroptosis. Furthermore, the combination of oxaliplatin and GW4064 synergistically inhibited STAT3 signaling by restoring SHP expression.Conclusions Our study revealed that GW4064 could enhance the antitumor effects of oxaliplatin against CRC, which provides a novel therapeutic strategy based on a combinational approach for CRC treatment.

scholarly journals A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

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