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        Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells

        Peng Song,Yang Hai,Xin Wang,Longhe Zhao,Baoqiang Chen,Peng Cui,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.4

        Realgar (As4S4), as an arsenic sulfide mineraldrug, has a good therapeutic reputation for anticancer inTraditional Chinese Medicine, and has recently beenreported to inhibit angiogenesis in tumor growth. However,considering the poor solubility and low bioavailability ofrealgar, large dose of realgar and long period of treatmentare necessary for achieving the effective blood medicineconcentration. In present study, we resolved the crucialproblem of poor solubility of realgar by using intrinsicbiotransformation in microorganism, and investigatedunderlying mechanisms of realgar transforming solution(RTS) for antiangiogenesis. Our results demonstrated thatRTS had a strong activity to inhibit HUVECs proliferation,migration, invasion, and tube formation. Moreover, RTSinhibited VEGF/bFGF-induced phosphorylation ofVEGFR2 and the downstream protein kinases includingERK, FAK, and Src. In vivo zebrafish and chickenchorioallantoic membrane model experiments showed thatRTS remarkably blocked angiogenesis. Finally, comparedwith the control, administration of 2.50 mg/kg RTSreached more than 50% inhibition against H22 tumorallografts in KM mice, but caused few toxic effects in thehost. The antiangiogenic effect was indicated by CD31immunohistochemical staining and alginate-encapsulatedtumor cell assay. In summary, our findings suggest thatRTS inhibits angiogenesis and may be a potential drugcandidate in anticancer therapy.

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        Photobiomodulation Facilitates Rat Cutaneous Wound Healing by Promoting Epidermal Stem Cells and Hair Follicle Stem Cells Proliferation

        Wang Tong,Song Yajuan,Yang Liu,Liu Wei,He Zhen’an,Shi Yi,Song Baoqiang,Yu Zhou 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.1

        Background: Cutaneous wound healing represents a common fundamental phenomenon requiring the participation of cells of distinct types and a major concern for the public. Evidence has confirmed that photobiomodulation (PBM) using near-infrared (NIR) can promote wound healing, but the cells involved and the precise molecular mechanisms remain elusive. Methods: Full-thickness skin defects with a diameter of 1.0 cm were made on the back of rats and randomly divided into the control group, 10 J, 15 J, and 30 J groups. The wound healing rate at days 4, 8, and 12 postoperatively was measured. HE and Masson staining was conducted to reveal the histological characteristics. Immunofluorescence staining was performed to label the epidermal stem cells (ESCs) and hair follicle stem cells (HFSCs). Western blot was performed to detect the expressions of proteins associated with ESCs and HFSCs. Cutaneous wound tissues were collected for RNA sequencing. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analysis was performed, and the hub genes were identified using CytoHubba and validated by qRT-PCR. Results: PBM can promote reepithelialization, extracellular matrix deposition, and wound healing, increase the number of KRT14+/PCNA+ ESCs and KRT15+/PCNA+ HFSCs, and upregulate the protein expression of P63, Krt14, and PCNA. Three hundred and sixty-six differentially expressed genes (DEGs) and 7 hub genes including Sox9, Krt5, Epcam, Cdh1, Cdh3, Dsp, and Pkp3 were identified. These DEGs are enriched in skin development, cell junction, and cadherin binding involved in cell–cell adhesion etc., while these hub genes are related to skin derived stem cells and cell adhesion. Conclusion: PBM accelerates wound healing by enhancing reepithelialization through promoting ESCs and HFSCs proliferation and elevating the expression of genes associated with stem cells and cell adhesion. This may provide a valuable alternative strategy to promote wound healing and reepithelialization by modulating the proliferation of skin derived stem cells and regulating genes related to cell adhesion. Background: Cutaneous wound healing represents a common fundamental phenomenon requiring the participation of cells of distinct types and a major concern for the public. Evidence has confirmed that photobiomodulation (PBM) using near-infrared (NIR) can promote wound healing, but the cells involved and the precise molecular mechanisms remain elusive. Methods: Full-thickness skin defects with a diameter of 1.0 cm were made on the back of rats and randomly divided into the control group, 10 J, 15 J, and 30 J groups. The wound healing rate at days 4, 8, and 12 postoperatively was measured. HE and Masson staining was conducted to reveal the histological characteristics. Immunofluorescence staining was performed to label the epidermal stem cells (ESCs) and hair follicle stem cells (HFSCs). Western blot was performed to detect the expressions of proteins associated with ESCs and HFSCs. Cutaneous wound tissues were collected for RNA sequencing. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analysis was performed, and the hub genes were identified using CytoHubba and validated by qRT-PCR. Results: PBM can promote reepithelialization, extracellular matrix deposition, and wound healing, increase the number of KRT14+/PCNA+ ESCs and KRT15+/PCNA+ HFSCs, and upregulate the protein expression of P63, Krt14, and PCNA. Three hundred and sixty-six differentially expressed genes (DEGs) and 7 hub genes including Sox9, Krt5, Epcam, Cdh1, Cdh3, Dsp, and Pkp3 were identified. These DEGs are enriched in skin development, cell junction, and cadherin binding involved in cell–cell adhesion etc., while these hub genes are related to skin derived stem cells and cell adhesion. Conclusion: PBM accelerates wound healing by enhancing reepithelialization through promoting ESCs and HFSCs proliferation and elevating the expression of genes associated with stem cells and cell adhesion. This may provide a valuable alternative strategy to promote wound healing and reepithelialization by modulating the proliferation of skin derived stem cells and regulating genes related to cell adhesion.

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