iScience
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2025
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IF 4.1
Shuyuan Chang,Ayaka Tomii,Yunfei Zhou,Xun Yang,Yihong Dong,Jun Yan,Aodi Wu,Yumeng Wang,Qingxin Zhang,Hongxue Meng,Lei Yu,Wei Sun,Dabin Liu
Succinate is a crucial metabolite in the TCA cycle and contributes to cancer development. However, the role of exogenous succinate in hepatocellular carcinoma (HCC) is unclear. Here, we report that the concentration of succinate in HCC tissues is lower compared to adjacent normal tissues, as determined by spatial metabolomics and quantitative metabolomics analysis. Succinate supplementation exhibits an anti-tumorigenic effect, inhibiting cell proliferation and colony formation in liver cancer cells but not in non-tumor LO2 cells. Additionally, succinate supplementation significantly reduces tumor formation in xenograft nude mice models and carcinogen-induced WT mice models. The anti-tumorigenic function of succinate is mechanistically mediated by FN1-activated SQLE-related cholesterol biosynthesis. Our study demonstrates that exogenous succinate acts as a cholesterol biosynthesis inhibitor to suppress HCC both in vitro and in vivo , highlighting its potential therapeutic applications.
研究领域:
肿瘤学
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代谢组学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR BIOLOGY
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2023
·Vol. 69
·期 7
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IF 1.6
Jingmei Cao,Qing Zhao,Qing Jia,Yiming Li
Growing evidence suggested that long non-coding RNA (lncRNA) played a crucial role in the progression of ulcerative colitis (UC). Therefore, the purpose of this study is to understand how the lncRNA CBR3-AS1, which has been found to be up-regulated in UC, contributes to the bio-progression of the disease. To determine the concentration and relationship of the lncRNA CBR3-AS1, miRNA-145-5p, and FN1 in the LPS-induced Caco-2 model cells, qRT-PCR was employed in this study. Starbase was used to predict the target sites of the lncRNA CBR3-AS1 and the miRNA-145-5p, and Targetscan was used to predict the probable linking points of the FN1 and the miRNA-145-5p, which was confirmed by a twofold luciferase reporter test. The vitality of Caco-2 cells was determined using the CCK-8 and FCM tests. Using the ELISA kit, TNF, IFN, IL-6, and IL-17 were identified. The results of the experiment show that in Caco-2 cells treated with 10 ng/mL LPS, LncRNA CBR3-AS1 was up-regulated. Additionally, Caco-2 cells' LPS-induced apoptosis and inflammatory response were inhibited by lncRNA CBR3-AS1 inhibition. Dual-luciferase reporter experiments demonstrated that miRNA-145-5p and lncRNA CBR3-AS1 might connect. Moreover, miRNA-145-5p, which was shown to be poorly expressed in UC, was found to suppress inflammatory and apoptotic responses in Caco-2 cells activated by LPS. It's significant that FN1 was confirmed to be miRNA-145-5p's downstream target. Sh-CBR3-AS1's inhibitory effects were reversed by miRNA-145-5p knockdown, and the effects of the miRNA-145-5p inhibitor were reversed by sh-FN1. In conclusion, LncRNA CBR3-AS1 may offer a unique method for treating UC by suppressing the function of miRNA-145-5p, which is implicated in the development of UC.
研究领域:
分子生物学
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胃肠病学
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免疫学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Chunfan Huang,Xiaoqi Jing,Qianhu Wu,Kan Ding
Renal fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. However, there are no effective clinical available drugs for the treatment. Notoginsenoside from Panax notoginseng could ameliorate renal fibrosis. We hypothesized that polysaccharide from this herb might have similar bioactivity. Here, we elucidated structure of a novel pectin-like polysaccharide designed SQD4S2 with a netty antenna backbone of glucogalacturonan substituted by glucoarabinan, glucurogalactan and galactose residues from this herb. Interestingly, SQD4S2 could reverse the morphological changes of human renal tubular HK-2 cells induced by TGF-β. Mechanism study suggested that this bioactivity might associate with N-cadherin (CDH2), Snail (SNAI1), Slug (SNAI2) depression and E-cadherin (CDH1) enhancement. In addition, SQD4S2 could impede critical fibrogenesis associated molecules such as α-SMA, fibronectin , vimentin , COL1A1, COL3A1, FN1 and ACTA2 expression induced by TGF-β in HK-2 cells. Current findings outline a novel leading polysaccharide for against renal fibrosis new drug development.
研究领域:
药理学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Min Wu,Yitao Zhao,Meihan Tao,Meimei Fu,Yue Wang,Qi Liu,Zhihui Lu,Jinshan Guo
The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.
研究领域:
生物医学工程
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组织工程
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细胞生物能学
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再生医学
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产品关联
DOI
PubMed
高影响因子
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