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BACKGROUND: Hypertrophic scar is a skin fibrosis disease characterized by excessive proliferation of fibroblasts, epidermal thickening, and stratum corneum dysfunction. At present, the pathogenesis of Hypertrophic scar is still unclear. OBJECTIVE: To screen the core (Hub) genes and important signaling pathways in hypertrophic scar-related datasets based on bioinformatics, and then verify them by cell experiments to predict small molecule drugs that may have therapeutic effects on hypertrophic scar. METHODS: Datasets related to hypertrophic scar were searched from Gene Expression Omnibus (GEO) database, and differentially expressed genes were identified by R software analysis. Gene ontology and KEGG enrichment analyses were performed for differentially expressed genes. Protein-protein interaction network of differentially expressed genes was constructed using String online platform. Then, the key genes and core modules in the protein-protein interaction network were screened by Cytohubba and MCODE plugin-in Cytoscape software respectively, and the Hub genes were obtained by the intersection of the above key genes and the genes that formed the core module. Real-time fluorescent quantitative PCR was used to verify the difference in Hub gene mRNA expression between human hypertrophic scar and normal skin epidermal stem cells. The histological data from the Human Protein Atlas were used to verify the differences in the expression and distribution of Hub gene-encoded proteins in the two kinds of human tissues. Finally, the potential drugs for hypertrophic scar were predicted by the connectivity map database. RESULTS AND CONCLUSION: Among the identified differentially expressed genes, 102 genes were up-regulated and 702 genes were down-regulated. Gene ontology and KEGG analysis showed that the enriched signaling pathways and biological processes were mainly involved in tight junction, arachidonic acid metabolism, extracellular matrix receptor interaction, epidermal development and keratinization. Eight Hub genes were found to be closely related to the mevalonate pathway that regulates cholesterol metabolism, including HMGCS1, DHCR7, MSMO1, FDPS, MVK, HMGCR, MVD and ACAT2. Compared with the normal skin group, the mRNA expression of HMGCS1, DHCR7, MSMO1, FDPS, HMGCR, MVD and ACAT2 in the hypertrophic scar group decreased significantly (P < 0.05), while MVK mRNA expression had no significant change (P > 0.05). Except for MVK, the expression levels of other Hub gene-encoded proteins in normal skin tissue were higher than those in hypertrophic scar tissue (P < 0.05). The top 10 candidate drugs included protein kinase A inhibitor (H-89), serine protease inhibitor (Dabigatran-Etexilate), FLT3 inhibitor (sunitinib), among which resveratrol and β-sitosterol are plant extracts. To conclude, Hub genes closely related to mevalonate metabolism may affect the structure and function of the epidermis by regulating lipid metabolism, which may an important pathogenesis of hypertrophic scar. The small-molecule compounds identified in this study can be used as candidate drugs for the treatment of hypertrophic scar. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Aesthetic & Plastic Surgery is the property of Chinese Journal of Aesthetic & Plastic Surgery Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: At present, effective preventive and therapeutic measures for hypertrophic scar are still limited. In contrast, most of botanical herbs have few side effects and abundant sources, offering new ideas and approaches for the prevention and treatment for hypertrophic scar. OBJECTIVE: To explore the potential molecular mechanism of plant-derived β-sitosterol on hypertrophic scar fibroblasts by network pharmacology and molecular docking techniques and to initially verify it by cytological experiments. METHODS: Through the network pharmacology, the relevant database and software were used to screen the drug targets of β-sitosterol and obtain the hypertrophic scar-related disease targets. The potential (intersection) targets of β-sitosterol on hypertrophic scar were obtained. Cytoscape software and STRING database were used to construct the “drug-target-disease” network and protein-protein interaction network, and screen out the core targets in the protein-protein interaction network. Gene ontology (GO) biological function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of intersection targets were conducted through the DAVID database, and the signaling pathways and core target genes closely related to the intersection targets were further identified through literature analysis. AutoDock software was used to perform the molecular docking of β-sitosterol and core target proteins. In vitro cellular assays were used to verify the effects of β-sitosterol on proliferation, apoptosis, cell cycle distribution and mRNA expression of core target genes in human hypertrophic scar fibroblasts. RESULTS AND CONCLUSION: There were 56 intersection targets of β-sitosterol and hypertrophic scar and 10 core targets were identified in the protein-protein interaction network, including tyrosine kinase, mitogen-activated protein kinase 3 (MAPK3), cysteine protease 3 (CASP3), apolipoprotein E, estrogen receptor 1, sterol regulatory element-binding transcription factor 1, peroxisome proliferator-activated receptor alpha, C-reactive protein, intercellular adhesion molecule 1, and catalase. Combined with the literatures and the functional analysis of the KEGG and GO, the MAPK signaling pathway was further identified to be closely related to the intersection targets, and MAPK3 (ERK1-MAPK), CASP3, P53 and tumor necrosis factor were identified as the core targets. The molecular docking results indicated that β-sitosterol was well bound to the core target proteins. Cellular assays showed that 100 μmol/L β-sitosterol inhibited hypertrophic scar fibroblast proliferation, decreased mitochondrial membrane potential and induced apoptosis (P < 0.01), increased the proportion of G1-phase cells and decreased the proportion of S-phase cells (P < 0.05), upregulated the mRNA expression of CASP3, P53 and tumor necrosis factor (P < 0.05), and downregulated the mRNA expression of MAPK3 (P < 0.001). To conclude, β-sitosterol may induce cell apoptosis in hypertrophic scar fibroblasts by activating the tumor necrosis factor pathway and upregulating the expression of CASP3 and P53, while inhibiting the ERK-MAPK pathway to arrest cell cycle and thus reduce the proliferation of hypertrophic scar fibroblasts. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Aesthetic & Plastic Surgery is the property of Chinese Journal of Aesthetic & Plastic Surgery Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Chinese Journal of Aesthetic & Plastic Surgery is the property of Chinese Journal of Aesthetic & Plastic Surgery Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To evaluate the effect of preoperative pulmonary artery pressure on perioperative prognosis of the recipients with end-stage heart failure undergoing heart transplantation. Methods Clinical data of 105 recipients receiving heart transplantation were retrospectively analyzed. The mean pulmonary artery pressure (mPAP) was used as the diagnostic criterion. The optimal cut-off value of mPAP for predicting perioperative prognosis of heart transplant recipients was determined. According to the optimal cut-off value of mPAP, all recipients were divided into the low mPAP group (n=66) and high mPAP group (n=39). Intraoperative indexes (cardiopulmonary bypass time, aortic occlusion time, assisted circulation time and cold ischemia time of donor heart) and postoperative indexes [intra-aortic balloon pump (IABP) support rate, IABP support time, extracorporeal membrane oxygenation (ECMO) support rate, ECMO support time, mechanical ventilation time, length of ICU stay, incidence of moderate and severe tricuspid regurgitation and perioperative mortality rate] were compared between the low and high mPAP groups. The prognosis of the two groups was compared. Results The optimal cut-off value of mPAP in predicting clinical prognosis of heart transplant recipients was 30.5 mmHg. In the high mPAP group, the ECMO support rate and perioperative mortality rate were higher than those in the low mPAP group (both P<0.05). No significant differences were observed in the cardiopulmonary bypass time, aortic occlusion time, assisted circulation time, cold ischemia time of donor heart, IABP support rate, IABP support time, ECMO support time, mechanical ventilation time, length of ICU stay and incidence of moderate and severe tricuspid regurgitation between two groups (all P>0.05). No significant differences were noted in the 1-, 2-, 3- and 4- survival rates between two groups (all P>0.05). Conclusions Preoperative mPAP in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off value of mPAP in predicting perioperative prognosis of heart transplant recipients is 30.5 mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation. [ABSTRACT FROM AUTHOR]