PHYTOTHERAPY RESEARCH
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2021
·Vol. 35
·期 7
·3799-3811
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IF 5.882
Min Wen,Yubei Liu,Ruiying Chen,Ping He,Feihua Wu,Rui Li,Yining Lin
Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.
研究领域:
肝病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Xiaohui Xu,Xinyue Wang,Qiang Xie,Jingyao Wu,Kwangnak Koh,Hongxia Chen
Ternary MXene/AuNRs/pSC4 interface enables oriented antibody immobilization. • 1.15 ng mL −1 detection limit in serum, 10–200 ng mL −1 linear range. • Hydrophilic MXene/AuNRs surface resists biofouling without serum pretreatment. • 5.7× signal gain over single-component devices via synergistic amplification. • Clinically distinguishes PD patients from healthy controls ( p < 0.001). Parkinson's disease (PD) management requires point-of-care accessible tools for personalized monitoring of levodopa therapy. Plasma dopa decarboxylase (DDC), a drug-responsive biomarker, has emerged as a promising target to guide dosing and anticipate adverse effects. However, current DDC assays rely on costly, labor intensive platforms that preclude rapid, sensitive detection in complex biological fluids. Here we report an electrochemical biosensor based on a novel ternary supramolecular interface combining MXene, Au nanorods, and p-sulfonatocalix[4]arene (pSC₄). In this design, pSC₄ serves as a supramolecular adapter to orient anti DDC antibodies via host–guest recognition, while the MXene/AuNRs hybrid provides synergistic signal amplification and contributes to reduced nonspecific adsorption. The sensor achieves a detection limit of 1.15 ng mL −1 and a linear range of 10–200 ng mL −1 in undiluted human serum, representing an approximately 5.7 fold signal amplification over single component devices. In an exploratory study of 12 subjects (6 PD patients under chronic dopaminergic therapy, 6 healthy controls), sera from PD patients showed a significantly higher ΔRct than controls (approximately threefold, P < 0.001). This work establishes an analytical proof-of-concept for DDC detection by integrating supramolecular chemistry with nanomaterials, providing a foundation for future clinical studies. Download: Download high-res image (109KB) Download: Download full-size image
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DOI
高影响因子
CELL PROLIFERATION
·
2024
·
IF 5.9
Yaqing Chen,Yi Yan,Yujing Li,Liang Zhang,Tingting Luo,Xinlong Zhu,Dan Qin,Ning Chen,Wendong Huang,Xiangmei Chen,Liqiang Wang,Xianmin Zhu,Lisheng Zhang
Transglutaminase 2 (Tgm2) plays an essential role in hepatic repair following prolonged toxic injury. During cholestatic liver injury, the intrahepatic cholangiocytes undergo dynamic tissue expansion and remodelling, referred to as ductular reaction (DR), which is crucial for liver regeneration. However, the molecular mechanisms governing the dynamics of active cells in DR are still largely unclear. Here, we generated Tgm2-knockout mice (Tgm2 −/− ) and Tgm2- CreERT2 -Rosa26-mTmG flox/flox (Tgm2 CreERT2 -R26T/G f/f ) mice and performed a three-dimensional (3D) collagen gel culture of mouse hepatocytes to demonstrate how Tgm2 signalling is involved in DR to remodel intrahepatic cholangiocytes. Our results showed that the deletion of Tgm2 adversely affected the functionality and maturity of the proliferative cholangiocytes in DR, thus leading to more severe cholestasis during DDC-induced liver injury. Additionally, Tgm2 hepatocytes played a crucial role in the regulation of DR through metaplasia. We unveiled that Tgm2 regulated H3K4me3Q5ser via serotonin to promote BMP signalling activation to participate in DR. Besides, we revealed that the activation or inhibition of BMP signalling could promote or suppress the development and maturation of cholangiocytes in DDC-induced DR. Furthermore, our 3D collagen gel culture assay indicated that Tgm2 was vital for the development of cholangiocytes in vitro. Our results uncovered a considerable role of BMP signalling in controlling metaplasia of Tgm2 hepatocytes in DR and revealed the phenotypic plasticity of mature hepatocytes.
研究领域:
肝病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 5
·2119
·
IF 4.9
Chengwei Wang,Chunjie Wu,Linjiang Song
Saiga antelope horn (SAH), a rare traditional Chinese medicine, exhibits activities of anti-feverish convulsions and anti-inflammation, whereas its underlying mechanism and specific pharmacological components are still unclear. In the present study, transient receptor potential ankyrin 1 (TRPA1), a major transient receptor potential cation channel was used as a target protein to identified TRPA1 high-affinity peptides (THPs) from SAH digests. Firstly, the SAH was digested under in vitro gastrointestinal conditions. With the method of affinity ultrafiltration and liquid chromatography–mass spectrometry (AUF-LC/MS), about 200 peptides that have a high-affinity interaction with the TRPA1 protein were screened from SAH digests. Subsequently, bioactivity databases and molecular docking were further exploited to identified three THPs, including RCWPDCR, FGFDGDF, and WFCEGSF. Furthermore, RIN-14B cells, characterized by the high expression of TRPA1 on cell surfaces, were used as the cell model to investigate the biological effect of THPs. Immunofluorescence and ELISA were conducted and showed that THPs can increase the intracellular Ca2+concentration and serotonin (5-HT) secretion in RIN-14B cells by activating TRPA1, which is evidenced by impaired upregulation of intracellular Ca2+levels and 5-HT secretion after pretreatment with the TRPA1 inhibitor (HC-030031). Moreover, an analysis of Western blots displayed that THPs up-regulated the expression levels of the 5-HT synthesis rate-limiting enzyme (TPH1) and 5-hydroxytryptophan decarboxylase (Ddc), while serotonin reuptake transporter (SERT) levels were down-regulated, suggesting that THPs enhance 5-HT secretion by regulating the 5-HT synthesis pathway. In summary, our findings demonstrate that THPs, which were identified from SAH digest via TRPA1-targeted affinity panning, exhibited the activation of the TRPA1 channel and enhanced 5-HT release in RIN-14B cells.
研究领域:
药理学
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分子生物学
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传统中药
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2022
·
IF 6.633
Huiwen Wang,Jian Zhang,Xiaoxun Zhang,Nan Zhao,Zongtao Zhou,Lijian Tao,Lei Fu,Shifang Peng,Jin Chai
Cholestasis is characterized by intrahepatic accumulation of bile acids (BAs), resulting in liver injury, fibrosis, and liver failure. To date, only ursodeoxycholic acid and obeticholic acid have been approved for the treatment of cholestasis. As fluorofenidone (AKF-PD) was previously reported to play significant anti-fibrotic and anti-inflammatory roles in various diseases, we investigated whether AKF-PD ameliorates cholestasis. A mouse model of cholestasis was constructed by administering a 0.1 % 3,5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) diet for 14 days. Male C57BL/6 J mice were treated with either AKF-PD or pirfenidone (PD) orally in addition to the DDC diet. Serum and liver tissues were subsequently collected and analyzed. We found that AKF-PD significantly reduced the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bile salts (TBA), as well as hepatic bile acids (BAs) levels. Hepatic histological analyses demonstrated that AKF-PD markedly attenuated hepatic inflammation and fibrosis. Further mechanistic analyses revealed that AKF-PD markedly inhibited expression of Cyp7a1, an enzyme key to BAs synthesis, by increasing Fxr nuclear translocation, and decreased hepatic inflammation by attenuating Erk/-Egr-1-mediated expression of inflammatory cytokines and chemokines Tnfα, Il-1β, Il-6, Ccl2, Ccl5 and Cxcl10. Moreover, AKF-PD was found to substantially reduce liver fibrosis via inhibition of Tgfβ1/Smad pathway in our mouse model. Here, we found that AKF-PD effectively attenuates cholestasis and hepatic fibrosis in the mouse model of DDC-induced cholestasis. As such, AKF-PD warrants further investigation as a candidate drug for treatment of cholestasis.
研究领域:
肝病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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