Roridin E, a constituent of Podostroma cornu-damae, has excellent medicinal properties and exhibits powerful anticancer effects. However, being a poisonous mushroom, P. cornu-damae is difficult to find in its natural environment. Therefore, only a limited amount of roridin E is isolated from P. cornu-damae. We isolated roridin E from mycelial culture medium of P. cornu-damae and examined its effects on five breast cancer cell lines. The purity of the isolated roridin E was 96%. It exhibited anticancer effects on all five breast cancer cell lines, with an IC50 of at least 0.0006 mg/L. To the best of our knowledge, this is the first report on the investigation of effects of roridin E isolated from the mycelium of P. cornu-damae mushrooms on five breast cancer cell lines. However, safety issues should be investigated and addressed in future studies before roridin E is used in clinical settings.

This case report describes satisfactory correction of deep and large canine corneal ulcerations by application of bidirectional corneo-conjunctival transposition (CCT). A 12-year-old spayed female Maltese dog with a large corneal descemetocele, perforation, and blepharospasm of the right eye was referred to Chungbuk National University Veterinary Teaching Hospital. More than half of the thickness of the cornea was damaged, and the ulcer was progressive. On ophthalmic examination, menace response and dazzle reflex were absent. No corneal melting was observed. As the patient had large and deep corneal ulcers, traditional one-sided CCT was not sufficient to cover the wound lesion. To increase corneal transparency after recovery, we decided to perform bidirectional CCT from 12 o’ clock on the dorsal side to 7 o’ clock on the ventral side. The dog was medicated with topical eye drops, ofloxacin, atropine, and moxifloxacin before surgery. Debridement with a diamond burr was then performed around the descemetocele. Five weeks after surgery, the dazzle reflex was restored as the blood vessel receded from the cornea to the conjunctiva. Eight weeks after surgery, corneal transparency and corneal stability were gradually restored, but not completely. Bidirectional CCT provides structural support and helps corneal wound healing in large canine corneal ulceration.

This study investigated the regenerative and healing effect of spirulina on corneal epithelial injury by acid burn in zebrafish. Corneal epithelium of adult zebrafish was evaluated at 0, 12, 24, 48 h after acid burn injury with or without immersion with 0.02 and 0.04 mg/mL of spirulina water extract. The pathological changes of corneal epithelium were assessed by light microscopy. Gene and protein expressions of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP) 9 and MMP13 were determined by immunohistochemistry or real-time PCR. Corneal epithelium was denuded totally after acid burn and gradually regenerated. PCNA-positive cells significantly increased in spirulina treated group. MMP9 and MMP13 mRNA transcripts were significantly decreased in spirulina treated groups. In conclusion, spirulina has regenerative and healing properties by increased keratocyte proliferation, and inhibited extracellular matrix degradation during the regeneration process of corneal epithelial injury by acid burn in zebrafish.

Astaxanthin(Ast) is considered a powerful antioxidant. However, the efficacy of Ast is limited due to its poor water solubility and stability. To enhance the properties of Ast, 2-hydroxypropyl-γ-cyclodextrin(HPγ-CyD) can be used through complexation. In this study, we investigated the wound healing ability of Ast/HP-γCyD(Ast/HP-γ-CyD) complex in sacran-based hydrogel. HP-γ-CyD played an important role to increase the elastic modulus of the sacran-based hydrogel with high swelling ability. Unusually, the Ast/HP-γ-CyD complex in sacran-based hydrogel provided the highest wound healing ability in mice. These results suggest that the Ast/HP-γ-CyD complex in sacran-based hydrogel has the potential for use as a new transdermal therapeutic system to promote the wound-healing process

The objective of the present study was to examine the effects of β-glucan originating from Aureobasidium on full-thickness skin wound healing in diabetic C57BL/KsJ-db/db mouse models. In the diabetic C57BL/KsJ-db/db model, test articles were topically applied twice a day for 20 days starting from 1 day after wounding. The results were compared to that of MadecassolTM ointment (madecassol; 1% Centella asiatica extracts) topically applied at a concentration of 100 mg/kg. Treatment with β-glucan resulted in significant (p<0.01 or p<0.05) and dose-dependent decreases in wound size compared with that of vehicle control showing increased wound size (WS, %). In addition, 50% contraction time (CT50) was dramatically and dose-dependently reduced, and inflammatory cells in granulation tissues of the wound area were significantly (p<0.01 or p<0.05) and dose-dependently reduced compared with that of vehicle control showing increased numbers of micro-vessels and fibroblasts as well as re-epithelialization. In the madecassol group, similar changes in inflammatory cells and fibroblasts with re-epithelialization were also observed, but madecassol did not influence angiogenesis. No meaningful changes in body weight were detected in all tested groups compared with the vehicle control. Therefore, these data suggest that β-glucan has a beneficial effect on diabetic delayed skin wound healing and may be useful to manage incurable skin wounds in diabetic animals.

This study investigated the effects of changes to the pulsation factor of pulsed direct currents on wound healing. Patients with a pressure ulcer at a care hospital for the elderly were randomly divided into three groups: Group 1 involved the application of 100㎲ in pulse duration, 10 ㎳ in pulse period, 100 pps in a pulsation factor, 15 ㎃ in pulse amplitude, and polarity red+ by using pulsed direct currents; Group 2 involved a change of pulse period to 8 ms; and Group 3 received general wound management. Although there were no statistically significant differences in the changing stages of pressure ulcers among the groups, all the groups dropped in numerical stages. In the two groups to which pulsed direct currents were applied, there was a statistically significant reduction in the stages of pressure ulcers from the initial assessment to the 12-week assessment (p<.05). Even though there were no statistically significant differences in changes to the area of pressure ulcers among the groups, a statistically significant decrease was found in pulsed direct current group 2 whose pulse period was shortened (p<.05). There was no difference in the healing rate of pressure ulcers among the groups, but it made a numerical increase in pulsed direct current group 1 and group 2 and a numerical decrease in group 3. There were no significant differences in the characteristics of those who had a full recovery among the groups. Those findings indicate that pulsed direct currents have positive effects on the wound healing of patients with a pressure ulcer and that a treatment with pulsed direct currents whose pulsation factor is raised by reducing the pulse duration is especially effective.

We pathologically investigated the effects of water irrigation during Er:YAG laser irradiation on wound healing in mouse skin. Fifty-one 6-week-old ICR male mice were used in the present study. Dermal wounds were generated on the skin of the backs using the Er:YAG laser at 100 mJ/pulse and 10 Hz with (4 ml/min) or without (control) water irrigation. Mice were then sacrificed on 0, 1, and 3 days after laser irradiation, and the crust of the skin and thickness of the thermal coagulation layer were evaluated pathologically. The epidermis extended faster in the water irrigation group than in the control group on 1 day. The epidermis with keratinized layers became thicker and the crust had completely detached after 3 days in the water irrigation group. The thermal coagulation layer was thinner in the water irrigation group than in the control group. Apoptotic cell death was prominent in the control group. Detachment of the crust was observed after 3 days in 50% of the water irrigation group and 20% of the control group. These results demonstrated that Er:YAG laser irradiation with water irrigation promoted faster wound healing

Royal jelly (RJ) is exclusive food that is secreted from the hypopharyngeal and mandibular glands of worker honeybees, and it is well known to be a necessary for the growth of the queen honeybee Although fresh royal jelly have been demonstrated to enhance wound healing, the wound healing effects of water soluble royal jelly (WSRJ) have not been elucidated. We investigated whether WSRJ promotes the migration, attachment, and proliferation of human dermal fibroblasts (HDFs) during in vitro wound healing. HDFs were treated with 1-5ug/ml WSRJ and RJ for up to 24hr following wound formation. Cell migration was assessed by measuring recovery from wound margin, while cell attachment and proliferation were determined by MTT assay. By observing the numbers of cell attached, we confirmed that not only WSRJ but also RJ did not affect on the initial cell adhesion. WSRJ (5 ug/ml) enhanced cell migration rate approximately 84.3% in HDFs at 24hr, whereas RJ (5 ug/ml) increased cell migration rate 71.3% in HDFs at 24hr, which is similar to cell migration rate of WSRJ 1 ug/ml (73.7%). In cell proliferation assays, WSRJ induced an increase in the number of HDFs, compared with control and RJ. In conclusion, WSRJ promotes cell migration with increased cell proliferation in an in vitro wound healing model.

Experiments were conducted in order to assess the healing effect of bee venom (BV) cream on full-thickness skin wounds in rabbits. BV cream was compared with silver sulfadiazine (SS) as a topical medicament against a control on experimentally created full-thickness wounds. Two wounds measuring 2 × 2 cm were created bilaterally (four wounds/rabbit) on the dorsolateral aspect of the trunk of seven New Zealand white rabbits. Wound treatments were evenly distributed on four sites, using a Latin square design. The contact layer of wounds was treated with physiological saline (control), SS cream, and BV cream over a period of 28 days. Assessment of wound healing was based on scab hardness, wound exudates, wound area, unepithelialized granulation tissue, and histopathological findings. Topical application of BV and SS creams to wounds resulted in reduced inflammation, debridement of necrotic tissue, and promoted granulation and epithelialization. Wound healing was faster, with statistical significance in BV and SS treatments, compared to the control (P<0.05). Treatment with BV evoked an anti-inflammation effect in a rabbit model. BV cream produced a wound healing effect similar to that of commercially available SS cream. Anti-inflammation effect as a topical treatment with BV cream appears to be better than that with SS cream. These results suggest that topical application of BV cream may be an alternative treatment for full-thickness skin wounds.

LEDs have been shown to be a safe, efficient, light-weight, and less-expensive alternative to heal wound. LED irradiation at the same biostimulatory wavelength of previous laser studies have similar biochemical effects The purpose of present study is to evaluate the effects of wound healing by LED irradiation. Thirty 34-day-old sprague dawley were used for present study. 1.5mm diameter defected holes were formed in both ear lobes of rat by rubber dam punch. 635nm and 890nm irradiation was performed by LED for 2 weeks, followed by histologíc examination staíned with H&E and Masson trichrome. Also, RT-PCR was carried out to find out the mRNA expression level in gingival fjbroblast irradiated by 635nm for 1 hour. In gross exarnination, wound healing was observed in irradiated group comparing to control For microscopic exarnination, repair by connective tissues was filled in defects of irradiated group, while dense cellular bands consisting of fjbroblasts and capi llaries were found at the end of defect in control By staining of masson trichrome, amount of collagens were found in irradiated group. In a result of RT-PCR, mRNA expressions of TGF- ß , MMP-1,3 and Timp-3 were down-regulated in irradiated group comparing with their expression in control group. Taken together, LED irradiation increase the prolifeation and the activity of fibroblasts and down-regualted the TGF-ß , MMP- 1,3 and Timp- 3 mRNA, followed by activation of would healing.

The purpose of this study was to evaluate the effects of pulsed ultrasound on wound healing and observe during the wound healing process the distribution of mast cells according to histopathologic findings. Eighty Sprague Dawley rats which were divided into 4 groups received full thickness skin wounds on the back. Each of the 5 animals was sacrificed immediately and then sacrificed again 1, 3, 6, and 12 days after injury. Specimens from the wounds were removed during healing and routinely processed with a hematoxylin-eosin stain and a toluidine blue stain. The authors then observed the distribution of mast cells under a light microscope. The results of this study were as follows: The rate of wound healing and the length of the wounds of the pulsed ultrasound group II was significantly faster than group I on day 6 and day 12 (p<.001). Group III showed the most significant effect after12 days (p<.001). Group IV also showed a significant effect at 12 days (p<.01). A low-intensity ultrasound .5 resulted in a fast healing rate. During the wound healing process mast cells had a tendency to decrease in the acute inflammatory phase. During the wound healing process mast cells were thought to contribute to the healing of the wound.

The purpose of this study was to determine whether high voltage pulsed current stimulation (HVPCS) would enhance wound healing in neuropathic rabbits. Ten rabbits were assigned to either an experimental or a control group. The wounded part around the peripheral neuropathy of the experimental rabbits was stimulated for two hours twice a day for six days under the following conditions: pulse frequency 80 pps, pulse duration , and stimulation intensity 30~40 V. The results indicated that there was no difference in the wound closure between the experimental and control groups. The two groups showed similar aspects in collagen and reticulum, which were observed by colored Masson's trichome. While the rabbits in the control group had more or less thick fibers, the rabbits in the experimental group had thin and branched-shape fibers. The rabbits in the experimental group showed both strong responses in the shaping of elastic fibers and the increased aspects in fibroblast when compared with the control group.

This study was performed to assess the efficacy of high voltage pulsed galvanic current for the healing of wounds in rabbits. Skin wounds were created laterally on the flank of 12 domestic rabbits(). The wounds of each group were treated with an intensity of 170 V at a frequency of 70 pulses per second, which was applied for 30 minutes a day for 10 days. The experimental groups were randomly assigned to either EXP I (n=3), EXP II(n=3), EXP III(n=3) or control(n=3). Each group was stimulated under the following conditions : 1) EXP I (Negative polarity), 2) EXP II (Change in polarity, negative electrode stimulation during the first 3 days and then positive electrode stimulation from 4 to 10 days), 3) EXP III(Positive polarity), 4) control(No stimulation). An active electrode was placed over the wound and a dispersive electrode on the buttock. The rate of wound closure was compared with the original wound size, evaluated by a tracing film in each measurement period. Finally, on the wound in each group, skin tissue was excised for histological evaluation after treatment for 10 days. The results obtained are as follows : 1) It was found that the control group did not show a complete remodeling of epitherial layer and had a chronic inflammatory response. Judging from the irregularity of intercellular space and the loose alignment of connective tissue, these findings show that wound healing was delayed. 2) EXP I showed a significant bactericidal effect, but a moderate response of vasodilation. The rate of wound closure was slower when compared with EXP II, III. 3) EXP II showed a complete remodeling of epitherial layer and a positive repair of connective tissue. Its rate of wound closure was best when compared with the others. 4) EXP III had a slower rate of wound closure than EXP II, but judging from the greater proliferation of collagen fibers and the dense alignment of connective tissue, this positive electrode was very effective in the formation of neo - connective tissue.

While adipose-derived stem cell-conditioned medium (ADSC-CM) has been demonstrated to promote skin wound healing, the mechanism regulating this effect remains unelucidated. In this study, we aimed to investigate the role of Ell3 in the wound healing activity of ADSC-CM. In vitro analysis revealed that Ell3 suppression in ADSCs impairs the promotive activity of ADSC-CM on the proliferation and migration of mouse embryonic fibroblasts (MEF) and normal human dermal fibroblasts (NHDF). Consistently, the expression of MMP family genes, which regulate cell proliferation and migration, was significantly suppressed in MEF and NHDF treated with siEll3-transfected ADSC-CM. Proinflammatory cytokines, such as interleukin-1 and interleukin-6, were highly expressed in MEF treated with siEll3-transfected ADSC-CM. The wound healing activity of siEll3-transfected ADSC-CM was significantly lower than that of the control in vivo. Our results suggest that Ell3 may contribute to the inhibition of inflammatory response during skin wound healing.

본 연구에서는 피부재생 화장품 소재로 활용하고자 저분자화 시킨 Polydeoxynucleotide (PDRN)의 창 상 치유 효과를 조사하였다. 이를 위하여 연어 정소 유래 PDRN 단백질 제거공정, 내독소 제거공정을 거쳐 순수 분리 정제하였고 분자량 저감공정을 거쳐 기존 PDRN 보다 피부 침투율을 높인 고순도 PDRN을 제조하였다. 상처 치료 과정 중 PDRN 처리에 의한 효능을 평가하기 위해 sprague-dawley rats (SD)의 배부에 bioxy punch를 이용한 4개의 창상을 유발하고, 시료를 포함한 총 5종의 실험시료를 마리당 500 μL씩 도포한 후 7일 간격으로 4주간 피부조직 변화를 관찰하였다. 상처에 PDRN을 도포한 후, 절개된 상처의 표피화와 수축이 더 빨라졌고, 창상면적에 있어서 PDRN의 도포는 양성대조군인 FucidinⓇ 도포군과 비교하여 유의하게 줄어들었다. 염색한 조직의 현미경 관찰 결과에서는 양성대조군이 가장 빠르게 재상피화가 이루어졌으며, 그 다음으로는 PH 군, PD군, HA군으로 교원질 재합성 및 형성 수준을 보였다. 또한, 병변의 형질전환성장인자(TGF-β) 및 혈관 내피성장인자(VEGF) 등의 성장인자에서도 염색 조직의 결과와 유사하게 나타났다. 이러한 결과를 종합하여 볼 때, 저분자화된 PDRN은 창상에 치료효과가 있다고 판단되며, 화장품 및 의료산업 분야의 기능성 소재로 활용 가능할 것으로 판단되어 진다.

Prostaglandin (PG) E2 is an important mediator of skin wound healing without excessive scarring and gastric ulcer healing. However, PGE2 has a short lifetime in vivo because it is metabolized rapidly by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Ethanol extract of Eriobotryae folium (EFEE) elevated intracellular and extracellular PGE2 levels in HaCaT cells and inhibited 15-PGDH (ED50 : 168.4μg/mL) with relatively low cytotoxicity (IC50 : 250.0μg/mL). Real-time PCR analysis showed that mRNA expression of cyclooxygenase (COX)-1 and COX-2 enzymes were increased and prostaglandin transporter (PGT) was decreased in HaCaT cells by EFEE. Moreover, wound healing effect of EFEE (168.4μg/mL) was comparable to that of TGF-β1 (300 pg/mL) as a positive control. These results demonstrate that EFEE may be valuable therapeutic materials for the treatment of PGE2 level dependent diseases.