BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff...BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.展开更多
AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METH...AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METHODS: The alkali -burned rat corneas (32 right eyes) were treated with eye drops containing Nodinhibit-1 or phosphate buffered solution (PBS, pH 7.4) only, four times per day. CNV and inflammation were monitored using slit lamp microscopy, and the area of CNV was measured by formula. Vascular endothelial growth factor (VEGF) and pigment epithelium -derived factor (PEDF) was determined by Western blot analysis. The TUNEL assay was used to assess the corneal apoptosis cells. RESULTS: Alkali-burn-induced progressive CNV and inflammation in the cornea. After treatment for 7d and 14d, there were statistically significant differences in the CNV areas and inflammatory index on that between two group(P<0.05, respectively). Epithelial defect quantification showed a significant difference between the two groups at days 4 and 7 after the alkali burns (P<0.05). The apoptotic. cells on days 1, 4, and 7 between the two groups showed significant differences at all time points (P<0.05, respectively). Compared to that in control group, the protein level of VEGF expression was significantly reduced whereas the PEDF expression was increase in the Nodinhibit-1 groups on day 14(P<0.05, respectively). CONCLUSION: Topical application of 10.0 mu g/mL Nodinhibit -1 may have potential effect for the alkali burn -induced CNV and inflammation. The effect of Nodinhibit -1 on CNV may be by regulation the equilibrium of VEGF and PEDF in the wounded cornea.展开更多
Objective:To discuss the main active components and potential mechanisms of moist burn ointment in the treat-ment of diabetic ulcer were discussed by network pharmacology and molecular docking technology.Methods:Based...Objective:To discuss the main active components and potential mechanisms of moist burn ointment in the treat-ment of diabetic ulcer were discussed by network pharmacology and molecular docking technology.Methods:Based on the TC-MSP database,the main active components and targets of MEBO were screened.The targets related to diabetic ulcers were searched from GeneCards,OMIM,PharmGkb,TTD,and DrugBank databases.The STRING 11.5 database was used to con-struct a protein-protein interaction(PPI)network to screen the core targets.The'drug-target-disease'network diagram was made in Cytoscape 3.8.2 software to screen the core active components.GO enrichment analysis and KEGG pathway enrichment analysis were performed using R language software.Finally,molecular docking was used to preliminarily verify the screening results.Results:A total of 37 active components of MEBO were screened to map 100 targets,5527 targets for diabetic ulcer dis-ease,and 77 intersection targets.PPI network topology analysis suggested that TP53,TNF,HSP90AA1 and other targets were key targets;the network diagram of ‘drug-target-disease’showed that acacetin,wogonin,quercetin,and rutaecarpine were the core active ingredients.GO function analysis mainly involved angiogenesis,ion transport,diameter regulation,cytokine receptor binding,and other processes.KEGG enrichment analysis mainly included PI3K-Akt,AGE-RAGE,and other signaling pathways.Molecular docking showed that the core active ingredients and key targets had good docking activity.Conclusion:The treatment of diabetic ulcer with MEBO is the result of multi-component,multi-target,and synergistic regulation,which provides a theoretical basis for the clinical application of MEBO and the treatment of diabetic ulcer.展开更多
BACKGROUND Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis,dermis and even subcutaneous tissue (including muscle and bones).First ...BACKGROUND Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis,dermis and even subcutaneous tissue (including muscle and bones).First reported by Cordon in 1767,ACC is a rare disease with a low incidence of 1/100000 to 3/10000.Currently,there are 500 cases reported worldwide.ACC can be accompanied by other malformations.The onset mechanism of the disease remains unknown but is thought to be correlated to factors such as genetics,narrow uterus,foetal skin and amniotic membrane adhesion,use of teratogenic drugs in early pregnancy and viral infection.CASE SUMMARY In August 2018,we treated a newborn with ACC on the left lower limbs using a combination of ionic silver dressing and moist exposed burn ointment (MEBO) and achieved a satisfactory treatment outcome.The skin defects were observed on the external genitals and on areas from the left foot to 3/4 of the upper left side.Subcutaneous tissue and blood vessels were observed in the regions with skin defects.The following treatments were provided.First,the wound was rinsed with 0.9% sodium chloride solution followed by disinfection with povidone-iodine twice.And then MEBO was applied to the wound at a thickness of approximately 1 mm.After applying ionic silver dressing,the wound was covered with sterile gauze.The wound dressing was replaced every 2-3 d.At the 4-mo follow-up,the treatment outcome was satisfactory.There was minimal scar tissue formation,and limb function was not impaired.CONCLUSION The combination of ionic silver dressing and MEBO to ACC is helpful.展开更多
AIM:To investigate the potential effect and mechanism of leucine-richα-2-glycoprotein-1(LRG1)on corneal angiogenesis and lymphangiogenesis.METHODS:Corneal neovascularization and lymphatics were induced by establishin...AIM:To investigate the potential effect and mechanism of leucine-richα-2-glycoprotein-1(LRG1)on corneal angiogenesis and lymphangiogenesis.METHODS:Corneal neovascularization and lymphatics were induced by establishing alkali burn mouse model.Immunofluorescence staining was performed to detect the location of LRG1 in cornea tissues and to verify the source of LRG1-positive cells.Corneal whole-mount staining for CD31(a panendothelial cell marker)and lymphatic endothelial hyluronan receptor-1(LYVE-1;lymphatic marker)was performed to detect the growth of blood and lymphatic vessels after local application of exogenous LRG1 protein or LRG1 si RNA.In addition,expressions of the proangiogenic vascular endothelial growth factor(VEGF)related proteins were detected using Western blot analysis.RESULTS:LRG1 was dramatically increased in alkali burned corneal stroma in both the limbal and central areas.LRG1-positive cells in the corneal stroma were mainly derived from Vimentin-positive cells.Local application ofexogenous LRG1 protein not only aggravated angiogenesis but also lymphangiogenesis significantly(P<0.01).LRG1 group upregulated the levels of VEGF and the vascular endothelial growth factor receptor(VEGFR)family when compared with the phosphate-buffered saline(PBS)control group.We also found that LRG1-specific si RNA could suppress corneal angiogenesis and lymphangiogenesis when compared with the scramble si RNA-treated group(P<0.01).CONCLUSION:LRG1 can facilitate corneal angiogenesis and lymphangiogenesis through heightening the stromal expression of VEGF-A,B,C,D and VEGFR-1,2,3;LRG1-specific si RNA can suppress corneal angiogenesis and lymphangiogenesis in corneal alkali burn mice.展开更多
基金Supported by the Hospital Research Fund,No.SDFEYBS1805,No.SDFEYGJ2013 and No.XKTJ-HRC20210015Suzhou Science and Technology Development Project,No.SYS2020105,No.SKJY2021078 and No.2022SS43+2 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLZD2021002CNNC Elite Talent Program2022 State Key Laboratory of Radiological Medicine and Radiation Protection jointly built by Province and Ministry,No.GZK1202244.
文摘BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.
基金Supported by the National Natural Science Foundation of China(No.81400372,No.81300729,No.81160118)Clinical Medicine Research Special-purpose Foundation of China(No.L2012052)+6 种基金Jiangxi Province Sailing Engineering(No.2014022)Shan Hai Foundation of China(No.2013SH008)Science Technology Foundation of Jiangxi Province(No.20151BBG70223)Youth Science Foundation of Jiangxi Province(No.20151BAB215016)Natural Science Foundation of Fujian Province(No.2015J05170)Education Department Youth Scientific Research Foundation(No.GJJ14170)Health Development Planning Commission Science Foundation of Jiangxi Province(No.20155154)
文摘AIM: To evaluate the therapeutic effect of Nodinhibit-1 on alkali-burn-induced corneal neovascularization (CNV) and inflammation. The nucleotide-binding oligomerzation domain 1 (NOD1) is a potent angiogenic gene. METHODS: The alkali -burned rat corneas (32 right eyes) were treated with eye drops containing Nodinhibit-1 or phosphate buffered solution (PBS, pH 7.4) only, four times per day. CNV and inflammation were monitored using slit lamp microscopy, and the area of CNV was measured by formula. Vascular endothelial growth factor (VEGF) and pigment epithelium -derived factor (PEDF) was determined by Western blot analysis. The TUNEL assay was used to assess the corneal apoptosis cells. RESULTS: Alkali-burn-induced progressive CNV and inflammation in the cornea. After treatment for 7d and 14d, there were statistically significant differences in the CNV areas and inflammatory index on that between two group(P<0.05, respectively). Epithelial defect quantification showed a significant difference between the two groups at days 4 and 7 after the alkali burns (P<0.05). The apoptotic. cells on days 1, 4, and 7 between the two groups showed significant differences at all time points (P<0.05, respectively). Compared to that in control group, the protein level of VEGF expression was significantly reduced whereas the PEDF expression was increase in the Nodinhibit-1 groups on day 14(P<0.05, respectively). CONCLUSION: Topical application of 10.0 mu g/mL Nodinhibit -1 may have potential effect for the alkali burn -induced CNV and inflammation. The effect of Nodinhibit -1 on CNV may be by regulation the equilibrium of VEGF and PEDF in the wounded cornea.
基金National Natural Science Foundation Project (No.81774327)Guangxi Graduate Education Innovation Program Project (No.YCSW2023496)+1 种基金The"139"Plan for Senior and Secondary Backbone Talents in Guangxi Medicine (No.Gui Wei Ke Jiao Fa[2018]No.22)Graduate Innovation Program Project of Youjiang Ethnic Medical College (No.YXCXJH2022004)。
文摘Objective:To discuss the main active components and potential mechanisms of moist burn ointment in the treat-ment of diabetic ulcer were discussed by network pharmacology and molecular docking technology.Methods:Based on the TC-MSP database,the main active components and targets of MEBO were screened.The targets related to diabetic ulcers were searched from GeneCards,OMIM,PharmGkb,TTD,and DrugBank databases.The STRING 11.5 database was used to con-struct a protein-protein interaction(PPI)network to screen the core targets.The'drug-target-disease'network diagram was made in Cytoscape 3.8.2 software to screen the core active components.GO enrichment analysis and KEGG pathway enrichment analysis were performed using R language software.Finally,molecular docking was used to preliminarily verify the screening results.Results:A total of 37 active components of MEBO were screened to map 100 targets,5527 targets for diabetic ulcer dis-ease,and 77 intersection targets.PPI network topology analysis suggested that TP53,TNF,HSP90AA1 and other targets were key targets;the network diagram of ‘drug-target-disease’showed that acacetin,wogonin,quercetin,and rutaecarpine were the core active ingredients.GO function analysis mainly involved angiogenesis,ion transport,diameter regulation,cytokine receptor binding,and other processes.KEGG enrichment analysis mainly included PI3K-Akt,AGE-RAGE,and other signaling pathways.Molecular docking showed that the core active ingredients and key targets had good docking activity.Conclusion:The treatment of diabetic ulcer with MEBO is the result of multi-component,multi-target,and synergistic regulation,which provides a theoretical basis for the clinical application of MEBO and the treatment of diabetic ulcer.
文摘BACKGROUND Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis,dermis and even subcutaneous tissue (including muscle and bones).First reported by Cordon in 1767,ACC is a rare disease with a low incidence of 1/100000 to 3/10000.Currently,there are 500 cases reported worldwide.ACC can be accompanied by other malformations.The onset mechanism of the disease remains unknown but is thought to be correlated to factors such as genetics,narrow uterus,foetal skin and amniotic membrane adhesion,use of teratogenic drugs in early pregnancy and viral infection.CASE SUMMARY In August 2018,we treated a newborn with ACC on the left lower limbs using a combination of ionic silver dressing and moist exposed burn ointment (MEBO) and achieved a satisfactory treatment outcome.The skin defects were observed on the external genitals and on areas from the left foot to 3/4 of the upper left side.Subcutaneous tissue and blood vessels were observed in the regions with skin defects.The following treatments were provided.First,the wound was rinsed with 0.9% sodium chloride solution followed by disinfection with povidone-iodine twice.And then MEBO was applied to the wound at a thickness of approximately 1 mm.After applying ionic silver dressing,the wound was covered with sterile gauze.The wound dressing was replaced every 2-3 d.At the 4-mo follow-up,the treatment outcome was satisfactory.There was minimal scar tissue formation,and limb function was not impaired.CONCLUSION The combination of ionic silver dressing and MEBO to ACC is helpful.
基金Supported by the National Natural Science Foundation of China(No.81670828)the Shandong Provincial Key Research and Development Program(No.2017GSF18141).
文摘AIM:To investigate the potential effect and mechanism of leucine-richα-2-glycoprotein-1(LRG1)on corneal angiogenesis and lymphangiogenesis.METHODS:Corneal neovascularization and lymphatics were induced by establishing alkali burn mouse model.Immunofluorescence staining was performed to detect the location of LRG1 in cornea tissues and to verify the source of LRG1-positive cells.Corneal whole-mount staining for CD31(a panendothelial cell marker)and lymphatic endothelial hyluronan receptor-1(LYVE-1;lymphatic marker)was performed to detect the growth of blood and lymphatic vessels after local application of exogenous LRG1 protein or LRG1 si RNA.In addition,expressions of the proangiogenic vascular endothelial growth factor(VEGF)related proteins were detected using Western blot analysis.RESULTS:LRG1 was dramatically increased in alkali burned corneal stroma in both the limbal and central areas.LRG1-positive cells in the corneal stroma were mainly derived from Vimentin-positive cells.Local application ofexogenous LRG1 protein not only aggravated angiogenesis but also lymphangiogenesis significantly(P<0.01).LRG1 group upregulated the levels of VEGF and the vascular endothelial growth factor receptor(VEGFR)family when compared with the phosphate-buffered saline(PBS)control group.We also found that LRG1-specific si RNA could suppress corneal angiogenesis and lymphangiogenesis when compared with the scramble si RNA-treated group(P<0.01).CONCLUSION:LRG1 can facilitate corneal angiogenesis and lymphangiogenesis through heightening the stromal expression of VEGF-A,B,C,D and VEGFR-1,2,3;LRG1-specific si RNA can suppress corneal angiogenesis and lymphangiogenesis in corneal alkali burn mice.
