Theranostics
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2019
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IF 8.063
Yaodong Chen,Pengfei Liu,Peng Sun,Jian Jiang,Yuanbo Zhu,Tianxiu Dong,Yingzhe Cui,Yuan Tian,Tingting An,Jiuwei Zhang,Zizhuo Li,Xiuhua Yang
Glioblastoma multiforme (GBM) has been considered the most aggressive glioma type. Temozolomide (TMZ) is the main first-line chemotherapeutic agent for GBM. Decreased mutS homolog 6 (MSH6) expression is clinically recognized as one of the principal reasons for GBM resistance to TMZ. However, the specific functions of MSH6 in GBM, in addition to its role in mismatch repair, remain unknown. Methods: Bioinformatics were employed to analyze MSH6 mRNA and protein levels in GBM clinical samples and to predict the potential cancer-promoting functions and mechanisms of MSH6. MSH6 levels were silenced or overexpressed in GBM cells to assess its functional effects in vitro and in vivo . Western blot, qRT-PCR, and immunofluorescence assays were used to explore the relevant molecular mechanisms. Cu 2 (OH)PO 4 @PAA nanoparticles were fabricated through a hydrothermal method. Their MRI and photothermal effects as well as their effect on restraining the MSH6-CXCR4-TGFB1 feedback loop were investigated in vitro and in vivo . Results: We demonstrated that MSH6 is an overexpressed oncogene in human GBM tissues. MSH6, CXCR4 and TGFB1 formed a triangular MSH6-CXCR4-TGFB1 feedback loop that accelerated gliomagenesis, proliferation (G1 phase), migration and invasion (epithelial-to-mesenchymal transition; EMT), stemness, angiogenesis and antiapoptotic effects by regulating the p-STAT3/Slug and p-Smad2/3/ZEB2 signaling pathways in GBM. In addition, the MSH6-CXCR4-TGFB1 feedback loop was a vital marker of GBM, making it a promising therapeutic target. Notably, photothermal therapy (PTT) mediated by Cu 2 (OH)PO 4 @PAA + near infrared (NIR) irradiation showed outstanding therapeutic effects, which might be associated with a repressed MSH6-CXCR4-TGFB1 feedback loop and its downstream factors in GBM. Simultaneously, the prominent MR imaging (T1WI) ability of Cu 2 (OH)PO 4 @PAA could provide visual guidance for PTT. Conclusions: Our findings indicate that the oncogenic MSH6-CXCR4-TGFB1 feedback loop is a novel therapeutic target for GBM and that PTT is associated with the inhibition of the MSH6-CXCR4-TGFB1 loop.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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癌症治疗
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xinyue Zhang,Yawen Huang,Tao Luo,Chen Hu,Haihang Li,Xiaoju Fan,Kefeng Wang,Jie Liang,Yafang Chen,Yujiang Fan
Excessive fibrotic scar formation during skin defect repair poses a formidable challenge, impeding the simultaneous acceleration of wound healing and prevention of scar formation and hindering the restoration of skin integrity and functionality. Drawing inspiration from the structural, compositional, and biological attributes of skin, we developed a hydrogel containing modified recombinant human collagen type III and thiolated hyaluronic acid to address the challenges of regenerating skin appendages and improving the recovery of skin functions after injury by reducing fibrotic scarring. The hydrogel displayed favorable biocompatibility, antioxidant properties, angiogenic potential, and fibroblast migration stimulation in vitro. In a rat full-layer defect model, it reduced inflammation, promoted microvascular formation, and significantly enhanced the wound healing speed and effectiveness. Additionally, by upregulating fibrosis-associated genes, such as TGFB1, it facilitated collagen accumulation and a beneficial balance between type I and type III collagen, potentially expediting skin regeneration and functional recovery. In conclusion, the utilization of rhCol III-HS demonstrated considerable potential as a wound dressing, offering a highly effective strategy for the restoration and rejuvenation of complete skin defects.
研究领域:
组织工程
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伤口愈合
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生物材料
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Lei Qian,Hu Xu,Ruqiang Yuan,Weijing Yun,Yufang Ma
Formononetin, an isoflavone compound, has been extensively researched due to its various biological activities, including a potent protective effect on the cardiovascular system. However, the impact of formononetin on cardiac fibrosis has not been investigated. In this study, C57BL/6 mice were used to establish cardiac fibrosis animal models by subcutaneous injecting of isoproterenol (ISO) and formononetin was orally administrated. The results showed that formononetin reversed ISO-induced heart stiffness revealed by early-to-atrial wave ratio (E/A ratio). Masson staining, western blot, immunohistochemistry and real-time PCR exhibited that the cardiac fibrosis and fibrosis-related proteins (collage III, fibronectin, TGF-β1, α-SMA, and vimentin) and genes ( Col1a1 , Col3a1 , Acta2 and Tgfb1 ) induced by ISO were significantly suppressed by formononetin. Furthermore, by combining metabolomics and network pharmacology, we found three important targets ( ALDH2 , HADH , and MAOB ), which are associated with mitochondrial function, were involved in the beneficial effect of formononetin. Further validation revealed that these three genes were more abundance in cardiomyocyte than in cardiac fibroblast. The mRNA expression of ALDH2 and HADH were decreased, while MOAB was increased in cardiomyocyte upon ISO treatment and these phenomena were reversed by formononetin. In addition, we investigated mitochondrial membrane potential and ROS production in cardiomyocytes, the results showed that formononetin effectively improved mitochondrial dysfunction induced by ISO. In summary, we demonstrated that formononetin via regulating the expressions of ALDH2 , HADH, and MAOB in cardiomyocyte to improve mitochondrial dysfunction and alleviate β-adrenergic activation cardiac fibrosis.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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代谢组学
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）