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| 1 | Rho/ROCK pathway and neural regeneration: a potential therapeutic target for central nervous system and optic nerve damage显示文摘· Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway in vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cells was also discussed. · | Hai-Bo Tan Yi-Sheng Zhong Yu Cheng and Xi Shen | 2011 | International Journal of Ophthalmology(English edition)2011，4，6： | 31 |
| 2 | 基于活性筛选和靶标网络预测的蒲黄和赤芍选择性抑制血小板聚集作用显示文摘目的:探讨常用活血化瘀中药抗血小板活性的激动剂选择性及可能的作用通路。方法:通过体外高通量血小板聚集实验系统评价24种常用活血化瘀中药醇提取物抗二磷酸腺苷(ADP)和凝血酶诱导的血小板聚集活性;通过Ingenuity Pathway Analysis(IPA)预测代表性药物蒲黄与赤芍已知单体成分的作用靶点,并加以验证。结果:蒲黄抗ADP,凝血酶诱导血小板聚集的半数抑制浓度(IC50)分别为55.27,300.60 mg·L^(-1);赤芍抗ADP,凝血酶诱导血小板聚集的IC50分别为336.20,101.60 mg·L^(-1)。IPA预测提示,蒲黄与赤芍有可能通过调节Ca2+,环磷酸腺苷(c AMP)和一氧化氮(NO)水平抑制血小板聚集。实验发现,蒲黄可明显抑制ADP对血小板内Ca2+的升高(P<0.05,P<0.01);赤芍可显著提高凝血酶导致的血小板内NO浓度降低(P<0.01);蒲黄、赤芍均不能逆转ADP,凝血酶引起的血小板内c AMP浓度降低。结论:蒲黄和赤芍醇提物分别具有选择性抗ADP和凝血酶诱导的大鼠血小板聚集活性。与IPA预测相符,蒲黄可降低血小板内钙离子水平,赤芍可提高血小板内NO浓度,可能分别激活嘌呤能P2Y1受体下游的Gq亚基/磷脂酶C(PLC)/三磷酸肌醇(IP3)和磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)/内皮型一氧化氮合酶(e NOS)通路抑制血小板聚集。 | 王潇毅 田晓轩 张砚 吴红华 王跃飞 朱彦 | 2017 | 中国实验方剂学杂志2017，23，1： | 33 |
| 3 | Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway显示文摘Diabetic nephropathy(DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin(30 mg·kg^(-1) body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L^(-1) were selected for experiments. The DN rats were treated with Taxus chinensis orally(0.32, 0.64, and 1.28 g·kg^(-1)) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway. | WENG Hong-Bo HAN Wen-Ke XIONG Yan-Wen JIN Zhou-Hui LAN Zhen LIU Cheng ZHANG Xue-Mei PENG Wen | 2018 | Chinese Journal of Natural Medicines2018，16，2： | 28 |
| 4 | Pathways of Influence of the Northern Hemisphere Mid–high Latitudes on East Asian Climate: A Review显示文摘This paper reviews recent progress made by Chinese scientists on the pathways of influence of the Northern Hemisphere mid-high latitudes on East Asian climate within the framework of a“coupled oceanic-atmospheric(land-atmospheric or seaice-atmospheric)bridge”and“chain coupled bridge”.Four major categories of pathways are concentrated upon,as follows:Pathway A—from North Atlantic to East Asia;Pathway B—from the North Pacific to East Asia;Pathway C—from the Arctic to East Asia;and Pathway D—the synergistic effects of the mid-high latitudes and tropics.In addition,definitions of the terms“combined effect”,“synergistic effect”and“antagonistic effect”of two or more factors of influence or processes and their criteria are introduced,so as to objectively investigate those effects in future research. | Jianping LI Fei ZHENG Cheng SUN Juan FENG Jing WANG | 2019 | Advances in Atmospheric Sciences2019，36，9： | 27 |
| 5 | Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma显示文摘Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to 'interval cancers'. If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap'', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates. | Takashi Murakami Naoto Sakamoto Akihito Nagahara | 2018 | World Journal of Gastroenterology2018，24，29： | 25 |
| 6 | Up-Regulation of Trem2 Inhibits Hippocampal Neuronal Apoptosis and Alleviates Oxidative Stress in Epilepsy via the PI3K/Akt Pathway in Mice显示文摘Epilepsy is a chronic and severe neurological disorder that has negative effects on the autonomous activities of patients. Functionally, Trem2(triggering receptor expressed on myeloid cells-2) is an immunoglobulin receptor that affects neurological and psychiatric genetic diseases. Based on this rationale, we aimed to assess the potential role of Trem2 integration with the PI3 K/Akt pathway in epilepsy. We used microarray-based gene expression profiling to identify epilepsy-related differentially-expressed genes. In a mouse hippocampal neuron model of epilepsy, neurons were treated with lowMg^2+ extracellular fluid, and the protein and mRNA expression of Trem2 were determined. Using a gain-offunction approach with Trem2, neuronal apoptosis and its related factors were assessed by flow cytometry, RT-qPCR,and Western blot analysis. In a pilocarpine-induced epileptic mouse model, the malondialdehyde(MDA) and8-hydroxy-20-deoxyguanosine(8-OHdG) content and superoxide dismutase(SOD) and glutathione-peroxidase(GSH-Px) activity in the hippocampus were determined,and the protein expression of Trem2 was measured. In addition, the regulatory effect of Trem2 on the PI3 K/Akt pathway was analyzed by inhibiting this pathway in both the cell and mouse models of epilepsy. Trem2 was found to occupy a core position and was correlated with epilepsy.Trem2 was decreased in the hippocampus of epileptic miceand epileptic hippocampal neurons. Of crucial importance,overexpression of Trem2 activated the PI3 K/Akt pathway to inhibit neuronal apoptosis. Moreover, activation of the PI3 K/Akt pathway through over-expression of Trem2 alleviated oxidative stress, as shown by the increased expression of SOD and GSH-Px and the decreased expression of MDA and 8-OHdG. The current study defines the potential role of Trem2 in inhibiting the development of epilepsy, indicating that Trem2 up-regulation alleviates hippocampal neuronal injury and oxidative stress, and inhibits neuronal apoptosis in epilepsy by activating the PI3 K/Akt pathway. | Ai-Hua Liu Min Chu Yu-Ping Wang | 2019 | Neuroscience Bulletin2019，35，3： | 25 |
| 7 | Pilose antler aqueous extract promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells by stimulating the BMP-2/Smad1, 5/Runx2 signaling pathway显示文摘Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not well understood. Here, PAAE was isolated and purified to explore the molecular mechanisms underlying PAAE’s effects on BMSCs as well as its osteoprotective effects in ovariectomized rats. Our results showed that PAAE promoted proliferation and differentiation of BMSCs to become osteoblasts by enhancing ALP activity and increasing extracellular matrix mineralization. The trabecular microarchitecture of ovariectomized rats was also found to be protected by PAAE. Quantitative reverse transcription-polymerase chain reaction(Quantitative RT-PCR) results suggest that PAAE also increased the expression of osteogenic markers including, alkaline phosphatase(ALP), runt-related transcription factor 2(Runx2), osteocalcin(OCN), bone morphogenetic protein-2(BMP-2), and collagen I(COL-I). Immunoblotting results indicated that PAAE upregulated the levels of BMP-2 and Runx2 and was associated with Smad1/5 phosphorylation. PAAE A at the concentration of 200μg·mL^-1 showed the strongest effect on proliferation and osteogenic differentiation of BMSCs after 48 h. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS), we identified the molecular weight of PAAE A and found that it is less than 3000 Da and showed several significant peaks. In conclusion, PAAE activates the BMP-2/Smad1, 5/Runx2 pathway to induce osteoblastic differentiation and mineralization in BMSCs and can inhibit OVX-induced bone loss. These mechanisms are likely responsible for its therapeutic effect on postmenopausal osteoporosis. | REN Cong GONG Wei LI Feng XIE Ming | 2019 | Chinese Journal of Natural Medicines2019，17，10： | 25 |
| 8 | Mechanisms of resistance to sorafenib and the corresponding strategies in hepatocellular carcinoma显示文摘Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc . Based on the investigated mechanisms,some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC. | Bo Zhai Xue-Ying Sun | 2013 | World Journal of Hepatology2013，5，7： | 24 |
| 9 | Total alkyl dibenzothiophenes content tracing the filling pathway of condensate reservoir in the Fushan Depression,South China Sea显示文摘The condensates are generally characterized by high maturity,low concentration of steranes and ter-panes biomarkers and low content of non-hydrocarbon fraction. In this case commonly used steranes,terpanes and carbazoles parameters cannot be effectively applied in the reservoir-filling tracing. The hydrogen bond formed by sulfur atom in the dibenzothiophenes (DBTs) results in molecule adsorption and fractionation during oil migration in reservoir. Like carbazoles,total DBTs content decreases with the increasing of oil migration distance. Therefore,a new parameter——total DBTs content is proposed to be used to trace the oil migration orientation and filling pathway. In present study,total DBTs con-tents of condensates and light oils are obtained by adding internal standard——eight deuterium atoms substituted DBT during Gas Chromatography-Mass Spectrometry analysis of aromatic fraction. Except for a few samples with much lower content of non-hydrocarbon fraction,the total DBTs content shows a fine positive correlation with that of carbazoles. Large errors can be caused in the process of pyrrolic nitrogen compounds separation. The application of this new parameter in the Fushan Depression of Beibu Gulf Basin,South China Sea indicates that this parameter is a reliable one to trace filling pathway in condensate reservoirs. Combined with other DBTs-related parameters,such as 4-/1-methydibenzo-thiophene and 2,4-/1,4-dimethyldibenzothiophene,oil migration orientation and filling pathway of the Fushan Depression was determined. The accumulations of Huachang oil field in the Fushan Depres-sion are mainly migrated and charged from northeast to southeast along the Huachang uplift. It can be predicated that the light oil and condensates in the Huachang oil field should be sourced from the source kitchen at the Bailian Sag. It shows that total DBTs content is an effective parameter to tracing oil migration orientation and filling pathway. | LI MeiJun1,WANG TieGuan1,LIU Ju2,ZHANG MeiZhu2,LU Hong3,MA QinLin2 & GAO LiHui2 1 State Key Laboratory of Petroleum Resources and Prospecting,Earth Sciences and Geoinformatics School,China University of Petroleum,Beijing 102249,China 2 Southern Oil Exploration and Development Company,PetroChina,Guangzhou 510640,China 3 Guangzhou Institute of Geochemistry,Chinese Academy of Sciences,Guangzhou 510240,China | 2008 | Science China Earth Sciences2008，51，S2： | 24 |
| 10 | Abnormal β-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China显示文摘AIM To study the abnormal expression of β-catenin gene and its relationship with invasiveness of primary hepatocellular carcinoma among Chinese people.METHODS Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, 4 normal liver tissues were immunohistochemically stained to study subcellular distribution of β-catenin. Semiquantitive analysis of expression of β-catenin gene exon 3 mRNA was examined by RT-PCR and in situ hybridization. The relationship between expressions of both β-catenin protein, mRNA and clinicopathological characteristics of HCC was also analyzed.RESULTS Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined displayed membranous type staining for β-catenin protein,occasionally with weak expression in the cytoplasm.While 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. The accumuled type Labling Index (LI) of cancer tissue and paracancarous tissue was (59.9 ± 26.3) and (18.3 ± 9.7)respectively (P<0.01). Higher accumulated type LI was closely related with invasiveness of HCC. Results of RTPCR showed the β-catenin gene exon 3 mRNA Expression Index (El) of 34 HCCs was higher than that of paracancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to β-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of para-cancerous and normal liver tissues. Over expression of β-catenin exon 3 was also found to be correlated with high metastatic potential of HCC.CONCLUSION Abnormal expression of β-catenin gene may contribute importantly to the invasiveness of HCC among Chinese people. | Maija H Zile | 2001 | World Journal of Gastroenterology2001，7，4： | 22 |
| 11 | Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats显示文摘AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis. | Ji-Wu Han,Department of Gastroenterology,The 4th Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China Xiao-Rong Zhan,Xin-Yu Li,Bing Xia,Yue-Ying Wang,Jing Zhang,Department of Endocrinology,First Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China Bao-Xin Li,Department of Pharmacology,State Key Laboratory of Biomedicine and Pharmacology,Harbin Medical University,Harbin 150001,Heilongjiang Province,China | 2010 | World Journal of Gastroenterology2010，16，48： | 22 |
| 12 | 普通油茶种子4个发育时期的转录组分析显示文摘我国油茶产业迅速发展,种苗繁育及栽培技术不断进步,但油茶分子基础研究薄弱,决定油茶产量、茶油质量、抗性等指标的重要经济、生长性状的分子机理研究甚少,这必将阻碍油茶产业的可持续发展。本项目首次采用高通量测序技术solexa技术对普通油茶'长林4号'无性系种子发育的4个时期转录组进行测序,经组装分析获得80 310条unigene,其中确定编码蛋白功能的有21 789条,分为24大类,占All-unigene的27.13%。通过与KEGG库比对,对42 638个unigene进行了Pathway注释,涉及的pathway有265个,主要包括新陈代谢、遗传信息加工、细胞代谢等相关pathway。这些相关研究为分析基因表达的数量及调控模式,分析基因表达调控元件的变化规律,揭示不同发育期基因表达差异等研究打下了良好基础,将为定向育种提供有力的理论指导和技术支持。 | 林萍 曹永庆 姚小华 王开良 滕建华 | 2011 | 分子植物育种2011，9，4： | 23 |
| 13 | Acacetin protects against cerebral ischemia-reperfusion injury via the NLRP3 signaling pathway显示文摘Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway. | Juan Bu Shen Shi Hui-Qin Wang Xiao-Shan Niu Zong-Feng Zhao Wei-Dong Wu Xiao-Ling Zhang Zhi Ma Yan-Jun Zhang Hui Zhang Yi Zhu | 2019 | Neural Regeneration Research2019，14，4： | 22 |
| 14 | Redox imbalance stress in diabetes mellitus: Role of the polyol pathway显示文摘In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase(AR) and sorbitol dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed. | Liang-jun Yan | 2018 | Animal Models and Experimental Medicine2018，1，1： | 22 |
| 15 | Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway显示文摘AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway. | Zhi-Gang Ma Xiao-Dan Lv Ling-Ling Zhan Lan Chen Qi-Yuan Zou Ji-Qiao Xiang Jiao-Li Qin Wei-Wei Zhang Zhao-Jing Zeng Hui Jin Hai-Xing Jiang Xiao-Ping Lv | 2016 | World Journal of Gastroenterology2016，22，6： | 21 |
| 16 | Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway显示文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is the most deadly type of tumor, and its pathogenesis remains unknown. Circular RNAs(circRNAs) may be functional and bind to micro RNAs and consequently, influence the activity of targeted mRNAs. Recent researches indicate that one circRNA, ciRS-7, acts as a sponge of miR-7 and thus, inhibits its activity. It is well known that miR-7 is a cancer suppressor in many cancers. However, the relationship between ciRS-7 and miR-7, and the role of ciRS-7 in PDAC, remains to be elucidated. Methods: miR-7 and ciRS-7 expression in 41 pairs of PDAC tumors and their paracancerous tissues were detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR). The relationships between their expression levels and clinicopathological features in PDAC tissues were assessed. The relationship between miR-7 and ciRS-7 was also assessed by Spearman’s correlation. We also used cell lines to evaluate the role of ciRS-7 in cell line behavior. The ciRS-7 interfere RNA(si RNA) and its empty vector were transfected into PDAC cells. PDAC cells proliferation and invasion abilities were detected by MTT assay and invasion analysis. The expression of proteins was assessed by Western blotting. Results: ciRS-7 expression was significantly higher in PDAC tissues than paracancerous tissues( P = 0.002). However, miR-7 expression showed the opposite trend( P = 0.048). Moreover, ciRS-7 expression was inversely correlated with miR-7 in PDAC( r s =-0.353, P = 0.023). ciRS-7 expression was also significantly elevated in venous invasion(3.72 ± 2.93 vs. 2.14 ± 1.26;P = 0.028) and lymph node metastasis(4.19 ± 2.75 vs. 2.32 ± 1.90;P = 0.016) in PDAC patients. Furthermore, ciRS-7 knockdown suppressed cell proliferation and invasion of PDAC cells( P < 0.05), and the downregulation of ciRS-7 resulted in miR-7 overexpression and subsequent inhibition of epidermal growth factor receptor(EGFR) and signal transducer and activator of transcription 3(STAT3). Conclusions: Circular RNA ciRS-7 plays an oncogene role in PDAC, partly by targeting miR-7 and regulating the EGFR/STAT3 signaling pathway. | Lei Liu Fu-Bao Liu Mei Huang Kun Xie Qing-Song Xie Chen-Hai Liu Min-Jing Shen Qiang Huang | 2019 | Hepatobiliary & Pancreatic Diseases International2019，18，6： | 21 |
| 17 | Up-regulation of PIK3CA promotes metastasis in gastric carcinoma显示文摘AIM:To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase(PI3K)/Akt pathway.METHODS:mRNA and protein levels of PIK3CA were assessed,respectively,by real-time quantitative polymerase chain reaction and immunohistochemistry in specimens of normal gastric mucosa,primary foci and lymph node and distant metastasis of gastric cancer.Akt and phosphorylated Akt protein were also examined by Western blotting in these tissues,in order to analyze the effect of PIK3CA expression level changes on the activation of PI3K/Akt signaling pathway.RESULTS:PIK3CA mRNA in lymph node metastasis were approximately 5 and 2 folds higher,respectively,than that in the corresponding normal gastric mucosa and primary gastric cancer tissues(P<0.05),while no statistical significance was found compared with distant metastasis.Immunohistochemically,PIK3CA protein expression was discovered in 7(35%)specimens of 20 primary foci vs 10(67%)of 15 of lymph node metastasis or 11(61%)of 18 of distant metastasis(35%vs 67%,P=0.015;35%vs 61%,P=0.044).With the increased level of PIK3CA expression,the total Akt protein expression remained almost unchanged,but p-Akt protein was upregulated markedly.CONCLUSION:Increased expression of PIK3CA is expected to be a promising indicator of metastasis in gastric cancer.Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt signaling. | Liu JF Zhou XK Chen JH Yi G Chen HG Ba MC Lin SQ Qi YC. | 2010 | World Journal of Gastroenterology2010，16，39： | 20 |
| 18 | Regulation and function of signal transducer and activator of transcription 3显示文摘Signal transducer and activator of transcription 3(STAT3), a member of the STAT family, is a key regulator of many physiological and pathological processes. Significant progress has been made in understanding the transcriptional control, posttranslational modification, cellular localization and functional regulation of STAT3. STAT3 can translocate into the nucleus and bind to specific promoter sequences, thereby exerting transcriptional regulation. Recent studies have shown that STAT3 can also translocate into mitochondria, participating in aerobic respiration and apoptosis. In addition, STAT3 plays an important role in inflammation and tumorigenesis by regulating cell proliferation, differentiation and metabolism. Conditional knockout mouse models make it possible to study the physiological function of STAT3 in specific tissues and organs. This review summarizes the latest advances in the understanding of the expression, regulation and function of STAT3 in physiological and tumorigenic processes. | Qian-Rong Qi Zeng-Ming Yang | 2014 | World Journal of Biological Chemistry2014，5，2： | 20 |
| 19 | Long noncoding RNA LINC00520 prevents the progression of cutaneous squamous cell carcinoma through the inactivation of the PI3K/Akt signaling pathway by downregulating EGFR显示文摘Background: Long noncoding RNAs (lncRNAs) play pivotal roles in various malignant tumors. Epidermal growth factor receptor (EGFR) signaling is associated with the pathogenesis of cutaneous squamous cell carcinoma (cSCC). This study aimed to explore the role of LINC00520 in the development of cSCC via EGFR and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways. Methods: A microarray analysis was applied to screen differentially expressed lncRNAs in cSCC samples. The A431 cSCC cell line was transfected and assigned different groups. The expression patterns of LINC00520, EGFR, and intermediates in the PI3K/Akt pathway were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Cell proliferation, migration, and invasion were detected using the MTT assay, scratch test, and Transwell assay, respectively. Cell-based experiments and a tumorigenicity assay were conducted to assess the effect of LINC00520 on cSCC progression. This study was ended in September 2017. Comparisons between two groups were analyzed with t-test and comparisons among multiple groups were analyzed using one-way analysis of variance. The nonparametric Wilcoxon rank sum test was used to analyze skewed data. The enumerated data were analyzed using the chi-square test or Fisher exact test. Results: Data from chip GSE66359 revealed depletion of LINC00520 in cSCC. Cells transfected with LINC00520 vector and LINC00520 vector + si-EGFR showed elevated LINC00520 level but decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the si-LINC00520 group showed opposite trends (all P < 0.05). Compared with the LINC00520 vector group, the LINC00520 vector + si-EGFR group showed decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the LINC00520 vector+ EGFR vector group showed opposite results (all P < 0.05). Conclusion: Based on our results, LINC00520-targeted EGFR inhibition might result in the inactivation of the PI3K/Akt pathway, thus inhibiting cSCC development. | Xue-Ling Mei Shah Zhong | 2019 | Chinese Medical Journal2019，，4： | 20 |
| 20 | Carotenoid Pigment Accumulation in Horticultural Plants显示文摘Carotenoids are a group of widely distributed natural pigments.They give many horticultural plants the bright red,orange,and yellow colors,as well as the aroma and flavor.Carotenoids enhance the health value and represent an essential quality trait of horticultural products.Significant efforts have been made to correlate specific carotenoid production with pathway gene expression.Some transcription factors that directly regulate transcription of the pathway genes have been identified.Horticultural crops have evolved with complicated and multifaceted regulatory mechanisms to generate the enormous diversity in carotenoid content and composition.However,the diverse and complex control of carotenoid accumulation is still not well understood.In this review,we depict carotenoid accumulation pathways and highlight the recent progress in the regulatory control of carotenoid accumulation in horticultural plants.Because of the critical roles of chromoplasts for carotenoid hyperproduction,we evaluate chromoplast ultrastructures and carotenoid sequestrations.A perspective on carotenoid research in horticultural crops is provided. | Anna S.Hermanns Xuesong Zhou Qiang Xu Yaakov Tadmor Li Li | 2020 | Horticultural Plant Journal2020，6，6： | 20 |
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