• Journal of Ginseng Research
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• v.47 no.6
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• pp.784-794
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• 2023

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Lepr^db/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

• Molecules and Cells
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• v.37 no.9
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• pp.637-643
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• 2014

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.540-567
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• 2003

Metabolic disease such as diabetes, which is caused by stress or imbalanced diet, has been increasing. A diabetic tend to suffer from a delay or difficulty of wound healing. The extract of SHIKON (SK), that is the root of Lithospermun erythrorhison, has been reported to have an effect on healing for normal wound, but has never studies for intractable wound so far. Therefore we examined the effect of SK extract on wound healing with healing impaired mouse model. Full-thickness round wounds were created on the backs of db/db mice and applied SK, and we observed neovascularization and collagen synthesis, distribution of apoptotic cells, and vascular endothelial growth factor (VEGF)- positive cells in granulation tissue. After two weeks, a number of capillary vessel and collagen synthesis were increased in SK-treated wounds. Infiltration of VEGF-positive neutrophils was also seen in the wound, besides apoptotic fibroblasts and endothelial cells were appeared in the granulation tissue. After three weeks, the wound closed completely with SK-treated but not in control. These results suggest that SK enhanced neovascularization by VEGF and this kind of apoptosis process makes the scar smooth. In this study, it is obvious that SK also accelerates healing of intractable wound.

• Archives of Reconstructive Microsurgery
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• v.17 no.1
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• pp.28-35
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• 2008

The purpose of this study was to present the clinical analysis of the results of lateral arm free flap for small sized and infected diabetic foot ulcer around toes. From May 2006 to December 2007, Seven patients were included in our study. Average age was 52.8 years, six were males and one was female. All had infected diabetic foot ulcer and had exposures of bone or tendon structures. Ulcers were located around great toe in four patients, 4th toe in one and 5th toe in two. Three patients had osteomyelitis of metatarsal or phalanx. After appropriate control of infection by serial wound debridement and intravenous antibiotics, lateral arm flap was applied to cover remained soft tissue defects. Posterior radial collateral artery of lateral arm flap was reanastomosed to dorsalis pedis artery of recipient foot by end to side technique in all cases in order to preserve already compromised artery of diabetic foot. All flaps were designed over lateral epicondyle to get longer pedicle and averaged pedicle length was 8 cm. Two cases were used as a sensate flap to achieve protective sensation of foot. All flaps survived and provided satisfactory coverage of soft tissue defects on diabetc foot ulcers. All patients could achieve full weight-bearing ambulation. No patients has had recurrence of infection, ulceration and further toe amputations. There were three complications, a delayed wound healing of flap with surrounding tissue, a partial peripheral loss of flap and a numbness of forearm below donor site. All patients were satisfied with their clinical results, especially preserving their toes and could return to the previous activity levels. Lateral arm free flap could be recommend for infected diabetic foot ulcers around toes, to preserve toes, coverage of soft tissue defect and control of infection with low donor site morbidity.

• Journal of Korean Foot and Ankle Society
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• v.27 no.2
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• pp.49-54
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• 2023

Purpose: The present study examined the effectiveness of the preoperative ischemia-modified albumin (IMA) levels in predicting the healing period of amputation wounds in patients with diabetes mellitus following a non-traumatic below-knee amputation (BKA). Materials and Methods: This study enrolled 41 diabetic foot ulcer patients who underwent BKA at the authors' hospital diabetic foot center from April 2016 to April 2022. Among the 41 patients, 29 (70.7%) were male and 12 (29.3%) were female. Their mean age was 64.54±11.38 years (41~81 years). The mean follow-up period was 19.48±5.56 weeks (14~48 weeks) after BKA. The patients were divided into two groups (high IMA group and normal IMA group), which evaluated the healing period, wound dehiscence, and revision operation rate using a Fisher's exact test and Mann-Whitney U test. Three orthopedic surgeons performed stump wound evaluation, and they were evaluated as healing when all sutures were fused without oozing. Results: Thirty patients (73.2%) (group A) showed a high level of IMA (median: 91.2 U/mL), and 11 (26.8%) patients (group B) showed a normal range of IMA (median: 82.7 U/mL). In group A, the median period for wound healing took 1.4 weeks longer, which was significant (p=0.001). No statistical relationship was observed between wound dehiscence, revision operation rate, and IMA value. There was no correlation between the other risk factors (estimated glomerular filtration rate, HbA1c) and the wound healing period. Conclusion: Although there was a limitation in using IMA as the sole factor to predict the healing period of amputation wounds in patients after BKA, this study revealed a significant positive correlation between IMA and the period of stump healing after BKA. Therefore, the preoperative IMA levels may help predict the period of stump healing after BKA.

• Journal of Yeungnam Medical Science
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• v.40 no.4
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• pp.343-351
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• 2023

Diabetic foot is one of the most devastating consequences of diabetes, resulting in amputation and possibly death. Therefore, early detection and vigorous treatment of infections in patients with diabetic foot are critical. This review seeks to provide guidelines for the therapy and rehabilitation of patients with moderate-to-severe diabetic foot. If a diabetic foot infection is suspected, bacterial cultures should be initially obtained. Numerous imaging studies can be used to identify diabetic foot, and recent research has shown that white blood cell single-photon emission computed tomography/computed tomography has comparable diagnostic specificity and sensitivity to magnetic resonance imaging. Surgery is performed when a diabetic foot ulcer is deep and is accompanied by bone and soft tissue infections. Patients should be taught preoperative rehabilitation before undergoing stressful surgery. During surgical procedures, it is critical to remove all necrotic tissue and drain the inflammatory area. It is critical to treat wounds with suitable dressings after surgery. Wet dressings promote the formation of granulation tissues and new blood vessels. Walking should begin as soon as the patient's general condition allows it, regardless of the wound status or prior walking capacity. Adequate treatment of comorbidities, including hypertension and dyslipidemia, and smoking cessation are necessary. Additionally, broad-spectrum antibiotics are required to treat diabetic foot infections.

• Journal of Korean Foot and Ankle Society
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• v.16 no.4
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• pp.217-222
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• 2012

Purpose: The purpose of this study is to establish guidelines for ankle-brachial index (ABI), toe-brachial index (TBI) and toe pressure with regard to healing of diabetic foot amputation wound. Material and Methods: We designed a retrospective study that included patients with diabetic foot ulcer. From 2008 to 2011, 46 patients who had suffered from amputation of a foot due to diabetic foot ulcer were included in this study. We divided them into amputation-success group and amputation-revision group, and compared their ankle-brachial index (ABI), toe-brachial index (TBI) and toe pressure between two groups. Amputation-revision group is that first forefoot amputation is failed to heal successfully and need to have another proximal amputation. Results: Toe pressure was 78 mmHg (54~107) in the amputation success group, 0 mmHg (0~43) in the amputation revision group (p=0.000). Ankle-brachial index was 1.1650(1.0475~1.1975) in the amputation success group, 0.92(0.5275~1.0750) in the amputation revision group (p=0.05), and toe-brachial index was 0.6100(0.4050~0.7575) in the amputation success group, 0.00(0.00~0.4150) in the amputation revision group (p=0.04), respectively. Conclusion: ABI, TBI, toe pressure of amputation success group were significantly higher than those of amputation revision group.

• BMB Reports
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• v.55 no.11
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• pp.559-564
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• 2022

Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.12 no.1
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• pp.14-26
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• 1990

This study was undertaken to observe the histopathologic changes of the extraction wounds of diabetic rats when exposed to hyperbaric oxygen. A total of 50 rats (Spraque-Dawley strain) were used, which were all induced with diabetes using streptozotocin before the experiment. The experimental group was exposed to hyperbaric oxygen at 2.5atm. for 2 hours a day during the experimental period. The obtained results were summarized as follows : 1. Severe infiltration of inflammatory cells was observed in the initial stages of both the control and experimental groups. The infiltration showed a decreasing tendency at 3rd week in the experimental group, while severe inflammatory infiltration observed in the control group during the entire experimental period. 2. There was abundant proliferation of capillary blood vessels at 1st week after extraction in the experimental group, while moderate capillary growth in the control group was observed at 1st week after extraction. 3. Osteoblastic activity was started at 1st week after extraction in the experimental group, but there showed markedly delayed appearance in the control group, which showed at 2nd week after extraction. 4. The proliferation of fibroblasts showed rather in the experimental group at 1st week, but it was moderate in the control group at 1st week, 2nd week and 3rd week. 5. Epithelialization of the extraction wound was started at 2 days after extraction and reached its peak at 3rd week in the experimental group, while control group seemed to be delayed and incompleted during the experiment. With regard to these results, hyperbaric oxygen therapy disclosed an effective results on the healing of the extraction wound in diabetic rats under exposure at 2.5 atm for 2 hours daily.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.14 no.2
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• pp.89-111
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• 2001

In order to investigate the effects of GamiTakliSodocyum(GTS) on wound healing, migration of epidermis, formation of granulation tissue and number of capillary within the granulation tissue were measured in diabetic mice by local application and NZW rabbits by local application and prescription of medicine in vivo, and proliferation of human epidermal keratinocytes and human dermal fibroblasts and composition of extracellular matrix were measured in vitro. The results were summerized as follows. 1. $2\%,\;10\%$ GTS remarkably increased migration of epidermis in diabetic mice by local application. 2. $2\%,\;10\%$ GTS remarkably increased formation of granulation tissue, number of neovascularization within the granulation tissue in diabetic mice by local application. 3. 5\%,\;10\%$ GTS remarkably increased migration of epidermis in NZW rabbits by local application. 4. $5\%,\;10\%$ GTS remarkably increased fonnation of granulation tissue, number of neovascularization within the granulation tissue in NZW rabbits by local application. 5. $5\%,\;10\%$ GTS increased migration of epidennis in NZW rabbits by prescription of medicine. 6. $5\%,\;10\%$ GTS increased formation of granulation tissue, number of neovascularization within the granulation tissue in NZW rabbits by prescription of medicine. 7. GTS didn't show effect on the proliferation of human epidermal keratinocytes. 8. GTS increased the proliferation of cultured human dermal fibroblasts. 9. GTS increased the expression of procoliagen ${\alpha}1(I) mRNA in cultured human dermal fibroblasts. 10. GTS increased the expression of fibronectin mRNA in cultured human dennal fibroblasts according to dosage of GTS using northern blot hybridization but didn't increase, using RT-PCR. From the above results, it is conclude that GTS might use on wound healing.