MOLECULAR CARCINOGENESIS
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2019
·Vol. 58
·期 8
·1481-1491
·
IF 3.411
Yuan-yuan Guo,Chen Xu,Yan Fang,Cai-e Wang,Na Gao,Qiang Wen,Hai-ling Qiao
Cytochrome P450 2E1 (CYP2E1) is an important drug-metabolizing enzyme that has been recognized as one of the risk factors for hepatofibrosis. Macrophages play key roles in regulating hepatofibrosis progression and resolution. However, whether CYP2E1 is involved in the regulation of macrophage polarization during hepatofibrosis is still unclear. Herein, we measured CYP2E1 activity and the expression of CD163 (an M2 marker) and CD68 (a pan-macrophage marker) in hepatofibrotic tissue from HCC patients (n = 26) with comparison to normal liver tissue (n = 26). The relationship of CYP2E1 activity in vivo and the CD163/CD68 ratio (an indicator of M2 polarization), as well as the extent of hepatofibrosis, were evaluated in diethylnitrosamine (DEN)-treated Sprague-Dawley rats. Strikingly, CYP2E1 activity and expression of CD68 increased and the CD163/CD68 ratio decreased, especially in hepatofibrotic tissue with higher CYP2E1 activity. Expression of α-SMA, Ki67, and PCNA were positively correlated with CYP2E1 activity and inversely correlated with the CD163/CD68 ratio. Furthermore, CYP2E1 activity showed an inverse correlation with the CD163/CD68 ratio. Overall, high CYP2E1 activity aggravates hepatofibrosis by restraining M2 macrophage polarization, providing a novel insight for understanding the profibrotic activity of CYP2E1 and a promising avenue for hepatofibrosis therapy.
研究领域:
肝病学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2018
·
IF 3.115
Zhi-Yong Lei,Jing-Jing Chen,Zhi-Jian Cao,Ming-Zhang Ao,Long-Jiang Yu
Ethnopharmacological relevance In traditional Chinese medicine , the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection , hepatitis, enteritis , dysentery , nyctalopia , conjunctivitis, urticaria , and furuncle . However, no scientific investigation has been conducted on its wound healing potential. Aim of the study To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. Materials and methods The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68 , CCR7 (CD197), CD163, TGF-β1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. Results We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-β1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. Conclusion Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-β1 and α-SMA expression.
研究领域:
药理学
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民族药理学
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伤口愈合
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传统中药
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Xiao-guo Suo,Fang Wang,Chuan-hui Xu,Xiao-yan He,Jia-nan Wang,Yao Zhang,Wei-jian Ni,Hao Lu,Ming-lu Ji,Yuan He,Shuai-shuai Xie,Ya-ru Yang,Jia-gen Wen,Juan Jin,Qian Gong,Jun Li,Ming-ming Liu,Xiao-ming Meng
Renal fibrosis , a common feature of chronic kidney disease , causes the progressive loss of renal function, in which TGF-β 1 plays a critical role. In this study, we found that expression levels of TGF-β 1 and its receptor 1 (TGF-βR1) were both significantly increased in obstructive fibrosis kidneys. AZ12601011 is a small molecular inhibitor of TGF-βR1; however, its therapeutic potential for renal fibrosis remains unclear. During the experiments, AZ12601011 was applied to various models of renal fibrosis followed by unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R) in vivo , in addition to renal tubular epithelial cells (TECs) challenged by hypoxia/reoxygenation (H/R) and TGF-β 1 in vitro. Our results revealed that AZ12601011 ameliorated renal injuries and fibrosis shown by PAS, HE , and Masson staining , which was consistent with the decrease in Col-1 and α-SMA expression in the kidneys from UUO and I/R mice. Similarly, in vitro data showed that AZ12601011 inhibited the induction of Col-1 and α-SMA in both TECs treated with TGF-β 1 and H/R. In addition, the results of cellular thermal shift assay (CETSA), molecular docking , and western bolt indicated that AZ12601011 could directly bind to TGF-βR1 and block activation of the downstream Smad3. Taken together, our findings suggest that AZ12601011 can attenuate renal fibrosis by blocking the TGF-β/Smad3 signaling pathway and it might serve as a promising clinical candidate in the fight against fibrotic kidney diseases.
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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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2018
·
IF 3.457
Lifeng Qin,Jinmei Qin,Xiumei Zhen,Qian Yang,Liyi Huang
The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis . Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis . Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin . The alleviation of liver fibrosis with curcumin treatment was associated with a reduction of CXCL12, CXCR4, α-SMA and RhoA. In addition, curcumin markedly inhibited the proliferation and migration of HSC-T6 cells. This study indicates that curcumin could protect against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DERMATOLOGICAL TREATMENT
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2020
·
IF 2.156
Yifeng Xiao
Background This study explored the function and mechanism of miR-486-5p in HSFBs.Methods Qualitative real-time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-486-5p in HS and hypertrophic scar fibroblasts (HSFBs). Viability, migration, invasion ability, apoptosis, and expressions of Collagen I, Collagen III, α-SMA and Cleaved caspase-3 in HSFBs after transfection with miR-486-5p mimic or inhibitor were measured by CCK-8, wound-healing, transwell, and Western blot, respectively. Interaction between miR-486-5p and IGF1 was predicted by Targetscan version 7.2 and further confirmed by dual-luciferase assay, and functional rescue experiments were conducted to verify the predicted molecular mechanism. The activation of PI3K/AKT pathway was also analyzed by Western blot.Results MiR-486-5p was low-expressed in HS and HSFBs, and that overexpression of miR-486-5p suppressed the viability, migration, invasion, and expressions of Collagen I, Collagen III, and α-SMA of HSFBs, meanwhile, it also promoted apoptosis and Cleaved caspase-3 expression in HSFBs. Moreover, IGF1 was targeted by miR-486-5p, and increased viability, migration, invasion, and collagens expressions, the activation of PI3K/Akt pathway, and decreased apoptosis and Cleaved caspase-3 induced by miR-486-5p inhibitor could be partly alleviated by siIGF1.Conclusions Overexpressed miR-486-5p inhibited the hyperproliferation and excessive production of collagen in HSFBs via IGF1/PI3K/AKT pathway.
研究领域:
分子生物学
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细胞生物学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2020
·Vol. 11
·期 5
·4582-4590
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IF 4.171
Xiaohua Lei,Qiang Liu,Qiang Liu,Zhenyu Cao,Ju Zhang,Tao Kuang,Yu Fang,Guoxing Liu,Ke Qian,Jie Fu,Huihui Du,Zhiqiang Liu,Zhihong Xiao,Changzhu Li,Xundi Xu
Liver fibrosis is a common part of the pathological development of many chronic liver diseases. As liver fibrosis progresses, it may lead to cirrhosis, portal hypertension, liver decompensation, liver tumours, and death. Camellia oil (Camellia oleifera Abel.) is widely used as an edible oil in China. It has a wide range of biological activities and is used as a traditional medicine to treat conditions such as burns and stomach pains. However, whether camellia oil can ameliorate liver fibrosis remains unclear. We constructed a liver fibrosis model induced by carbon tetrachloride (CCl4) and then confirmed the role of camellia oil in liver fibrosis by biochemical examination, histopathological morphology, immunohistochemistry, and western blot analysis. We found that camellia oil ameliorated histopathological lesions, improved liver function and antioxidant capacity, decreased the expression of TGF-β1 and α-SMA proteins, and downregulated the expression of the pro-apoptotic proteins in CCl4-induced liver fibrosis. Therefore, these results suggest that camellia oil attenuates CCl4-induced liver fibrosis in mice, and its mechanism may function via reduction of hepatocyte apoptosis to inhibit hepatic stellate cell (HSC) activation. Camellia oil may provide a potential new treatment for liver fibrosis as an auxiliary treatment by addition of the edible oil to the daily diet.
研究领域:
药理学
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肝病学
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病理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yi Lin,Wangdu Luo,Bingcai Jiang,Qianyi Lin,Min Tang,Xiangji Li,Lin Xie
Excessive scarring is the main cause of surgical failure in glaucoma filtration surgery. S58 has been shown to have an excellent antifibrotic effect but its duration of action is not sufficient to achieve the desired antiscarring effect. In this study, a light-cured bioadhesive hydrogel composed of GelMA and oxidized dextran (ODex), namely, GelDex, was used to load S58 (GelDex-S58). The microscopic morphology of GelDex-S58 appeared to be a porous structure with good slow-release properties and suitable degradation time. Cell Counting Kit-8, cell scratch and transwell assays showed that GelDex-S58 significantly reduced TGF-β-induced fibroblast proliferation, increased migration and invasion ability. In in vivo studies, GelDex-S58 treatment prolonged follicular retention, reduced mean intraocular pressure, and significantly reduced collagen deposition and α-SMA expression levels in the conjunctival tissue compared to treatment with S58 alone. In conclusion, GelDex-S58 could reduce scar formation after glaucoma filtration surgery.
研究领域:
眼科
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药学
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生物医学工程
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
·
IF 3.712
Fan Zhang,Jingxing Li,Chengxiong Gu,Haibo Zhang
Background The role and function of microRNA (miRNA, miR)-140-5p in the calcification of vascular smooth muscle cells (VSMCs) have been explored in this study.Methods The calcium nodules formed in transfected and β-glycerophosphate (β-GP)-treated VSMCs were observed using Alizarin Red S staining, and alkaline phosphatase (ALP) activity was determined. VSMC apoptosis was detected with flow cytometry assay. The target gene of miR-140-5p was predicted and confirmed with dual-luciferase reporter assay. Relative expressions of miR-140-5p, toll like receptor 4 (TLR4) and vascular calcification-related proteins (α-smooth muscle actin, α-SMA; Msh Homeobox 2, MSX2; bone morphogenetic protein 2, BMP2; Kruppel-like factor 4, KLF4; Runt-related transcription factor 2, RUNX2) were measured through quantitative real time polymerase chain reaction (qRT-PCR) and western blot.Results MiR-140-5p upregulation reversed the effects of β-GP on downregulating miR-140-5p and α-SMA expressions, enhancing ALP activity, calcium nodule formation and cell apoptosis, and upregulating levels of MSX2, BMP2, KLF4 and RUNX2. TLR4 was the target of miR-140-5p, and offset the effects of miR-140-5p on β-GP-induced VSMCs.Conclusions MiR-140-5p upregulation represses β-GP-induced calcification of VSMCs via targeting TLR4, providing a potential therapeutic method for vascular calcification.
研究领域:
分子生物学
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心血管疾病
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Gastrointestinal Surgery
·
2023
·
IF 2
Fan Ding,Run Guo,Fang Chen,Li-Ping Liu,Zheng-Yu Cui,Yi-Xing Wang,Gang Zhao,Hai Hu
BACKGROUND Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility. AIM To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. METHODS Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot. RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group. CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.
研究领域:
胃肠病学
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生理学
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病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Peng Wei,Zhang Shiwen,Zhou Wei,Zhao Xinchen,Wang Kexue,Yue Chengxu,Wei Xinyu,Pang Siyan,Dong Wei,Chen Sulian,Chen Changjie,Yang Qingling,Wang Wenrui
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
研究领域:
药理学
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细胞生物学
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肝病学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
·
2022
·Vol. 261
·期 3
·723-734
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IF 3.535
Zhou Jin,Ding Yuanyuan,Zhang Yongqiang,Zheng Dehui,Yan Lifeng,Guo Mengxiang,Mao Yani,Yang Lihong
Purpose This study was aimed at exploring the function of Exosomes isolated from bone marrow-derived mesenchymal stem cells (BMSC-Exos) in corneal wound healing and at revealing the underlying mechanisms involving the p44/42 mitogen-activated protein kinase (MAPK) pathway. Methods The isolated BMSC-Exos were identified by transmission electron microscopy, Western blot, and nanoparticle tracking analysis. After coculture with BMSC-Exos, the proliferation and migration of human corneal epithelial cells (HCEs) were evaluated. The protein expression of p-MEK/MEK and p44/42 MAPK was detected by Western blot. A mouse model of alkali-burned cornea was established via NaOH exposure. After injection with BMSC-Exos, the pathological changes and expression of α-SMA (a fibrosis marker) and CD31 (a vascularization marker) in corneal tissues were detected. Results BMSC-Exos enhanced the proliferation and migration of HCEs in a dose-dependent manner. The p44/42 MAPK pathway was activated by the treatment of BMSC-Exos, and its blocking using U0126 partially abrogated the effects of BMSC-Exos on promoting the proliferation and migration of HCEs. In vivo , the injection of BMSC-Exos facilitated the remission of the pathological changes (inflammation) and weakened the upregulation of α-SMA (fibrosis) and CD31 (vascularization) in corneal tissues of mice with alkali-burn injury. Conclusion BMSC-Exos promoted the proliferation and migration of HCEs via activating the p44/42 MAPK pathway in vitro and also inhibited alkali burn-induced inflammation, fibrosis, and vascularization in corneal tissues in vivo . BMSC-Exos may be promising resources for promoting corneal wound healing.
研究领域:
眼科学
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干细胞生物学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
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
·
肝病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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