CHEMICO-BIOLOGICAL INTERACTIONS
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2020
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IF 3.723
Yu Miao,Yanling Wu,Yingjin Jin,Mengze Lei,Jixing Nan,Xue Wu
Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone ( t Bu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SEPARATION SCIENCE AND TECHNOLOGY
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2022
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IF 2.799
Yu Zhang,Yun Jia,Yaoguo Huang,Linlin Chen,Ming Wang,Yali Zhang
In this study, thioacetamide (TAA) was used as the precipitant to selectively precipitate Cu2+, Cd2+, and Pb2+ in acidic solution. The effect of temperature, time, and pH conditions on the selective precipitation of metal ions were investigated. Meanwhile, the thermodynamic process of single metal precipitation was studied by Avrami equation. By continuously and accurately controlling pH, Cu2+, Cd2+, and Pb2+ were successfully precipitated at pH 2.5, 4.0, and 6.5, respectively. Traditional inorganic sulfide precipitator Na2S was also used to compare with TAA under the same conditions, and the results showed that compared with Na2S, TAA could be better to achieve the goal of selective precipitation of Cu2+, Cd2+, and Pb2+. The metal sulfide precipitation was measured by field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD).
研究领域:
环境化学
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分析化学
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材料科学
✓ 已验证
DOI
高影响因子
Journal of Cell Communication and Signaling
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2023
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IF 4.1
Zhao Ye,Wang Huiling,He Tianhua,Ma Bo,Chen Guoguang,Tzeng Chimeng
Liver fibrosis is an aberrant wound healing response to tissue injury characterized by excessive extracellular matrix deposition and loss of normal liver architecture. Hepatic stellate cells (HSCs) activation is regards to be the major process in liver fibrogenesis which is dynamic and reversible. Both Hippo signaling core factor Yap and Hedgehog (Hh) signaling promote HSCs transdifferentiation thereby regulating the repair process of liver injury. However, the molecular function of YAP and the regulation between Yap and Hh during fibrogenesis remain uncertain. In this study, the essential roles of Yap in liver fibrosis were investigated. Yap was detected to be increased in liver fibrotic tissue by the thioacetamide (TAA)-induced zebrafish embryonic and adult models. Inhibition of Yap by both embryonic morpholino interference and adult’s inhibitor treatment was proved to alleviate TAA-induced liver lesions by and histology and gene expression examination. Transcriptomic analysis and gene expression detection showed that Yap and Hh signaling pathway have a cross talking upon TAA-induced liver fibrosis. In addition, TAA induction promoted the nuclear colocalization of YAP and Hh signaling factor GLI2α. This study demonstrates that Yap and Hh play synergistic protective roles in liver fibrotic response and provides new theoretical insight concerning the mechanisms of fibrosis progression. Graphical abstract
研究领域:
分子生物学
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肝病学
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细胞信号传导
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Quanjuan Guo,Ailu Yang,Rongrong Zhao,Huajun Zhao,Yongliang Mu,Jian Zhang,Qiuju Han,Yuhang Su
Nimodipine, a calcium antagonist, exert beneficial neurovascular protective effects in clinic. Recently, Calcium channel blockers (CCBs) was reported to protect against liver fibrosis in mice, while the exact effects of Nimodipine on liver injury and hepatic fibrosis remain unclear. In this study, we assessed the effect of nimodipine in Thioacetamide (TAA)-induced liver fibrosis mouse model. Then, the collagen deposition and liver inflammation were assessed by HE straining. Also, the frequency and phenotype of NK cells, CD4 + T and CD8 + T cells and MDSC in liver and spleen were analyzed using flow cytometry. Furthermore, activation and apoptosis of primary Hepatic stellate cells (HSCs) and HSC line LX2 were detected using α-SMA staining and TUNEL assay, respectively. We found that nimodipine administration significantly attenuated liver inflammation and fibrosis. And the increase of the numbers of hepatic NK and NKT cells, a reversed CD4 + /CD8 + T ratio, and reduced the numbers of MDSC were observed after nimodipine treatment. Furthermore, nimodipine administration significantly decreased α-SMA expression in liver tissues, and increased TUNEL staining adjacent to hepatic stellate cells. Nimodipine also reduced the proliferation of LX2, and significantly promoted high level of apoptosis in vitro . Moreover, nimodipine downregulated Bcl-2 and Bcl-xl, simultaneously increased expression of JNK, p-JNK, and Caspase-3. Together, nimodipine mediated suppression of growth and fibrogenesis of HSCs may warrant its potential use in the treatment of liver fibrosis.
研究领域:
药理学
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免疫学
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肝病学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
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2023
·Vol. 14
·期 1
·1-19
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IF 16.6
Da Xingwen,Li Ziyan,Huang Xiaofan,He Zuhan,Yu Yubing,Tian Tongtong,Xu Chengqi,Yao Yufeng,Wang Qing K.
Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1 C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1 +/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1 smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1 +/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
研究领域:
心血管疾病
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
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2023
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IF 7.2
Weibin Chen,Chao Chen,Lei Li,Zhan Lin
Transition metal sulfides and their hybrids are promising alternative to precious metal catalyst for the oxygen evolution reaction (OER). Herein, the high-density Co 9 S 8 nanoparticles (NPs) embedded in N-doped carbon has been prepared by using surface-engineered zeolitic imidazolate framework-9 (ZIF-9) nanosheets as precursor. The surface of ZIF-9 was modified with TAA , which is able to create chemical barrier and prevents metal from aggregation in the subsequent pyrolysis , thus making small Co 9 S 8 NPs densely anchored on carbon layers . Arising from the unique structure, Co 9 S 8 @NC affords an optimized electronic structure and rich effective reactive sites for OER. As expected, Co 9 S 8 @NC exhibits small overpotential of 264 mV at 10 mA cm −2 , low Tafel slope of 68.4 mV dec −1 , and superior stability for alkaline OER (0.1 M KOH). The electrolysis cell , which was equipped with Co 9 S 8 @NC cathode and Pt/C anode, shows low water splitting voltage of 1.58 V at 10 mA cm −2 in 1.0 M KOH. This work employs an efficacious surface engineering strategy to design metal sulfide-based electrocatalysts for enhancing OER performance.
研究领域:
材料科学
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电化学
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催化
✓ 已验证
产品关联
DOI
高影响因子
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