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| 1 | Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance显示文摘AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis. | De Yun Feng Hui Zheng Yi Tan Rui Xue Cheng Department of Pathology, Hunan Medical University, Changsha 410078, Hunan Province, China New England Biolab, MA, USA | 2001 | World Journal of Gastroenterology2001，7，1： | 75 |
| 2 | 5'-Monophosphate-activated protein kinase (AMPK) improves autophagic activity in diabetes and diabetic complications显示文摘Diabetes mellitus(DM),an endocrine disorder,will be one of the leading causes of death world-wide in about two decades.Cellular injuries and disorders of energy metabolism are two key factors in the pathogenesis of diabetes,which also become the important causes for the process of diabetic complications.AMPK is a key enzyme in maintaining metabolic homeostasis and has been implicated in the activation of autophagy in distinct tissues.An increasing number of researchers have confirmed that autophagy is a potential factor to affect or induce diabetes and its complications nowadays,which could remove cytotoxic proteins and dysfunctional organelles.This review will summarize the regulation of autophagy and AMPK in diabetes and its complications,and explore how AMPK stimulates autophagy in different diabetic syndromes.A deeper understanding of the regulation and activity of AMPK in autophagy would enhance its development as a promising therapeutic target for diabetes treatment. | Fan Yao Ming Zhang Li Chen | 2016 | Acta Pharmaceutica Sinica B2016，6，1： | 24 |
| 3 | Mnk kinase pathway: Cellular functions and biological outcomes显示文摘The mitogen-activated protein kinase(MAPK) interacting protein kinases 1 and 2(Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs(p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E(eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4 E. The role of Mnk kinases in inflammation and inflammationinduced malignancies is also discussed. | Sonali Joshi Leonidas C Platanias | 2014 | World Journal of Biological Chemistry2014，5，3： | 16 |
| 4 | Shenfu injection attenuates lipopolysaccharide-induced myocardial inflammation and apoptosis in rats显示文摘Shenfu injection(SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide(LPS)-induced myocardial inflammation and apoptosis.Experiments were carried out in Sprague-Dawley(SD) rats treated with LPS or LPS + SFI, and in H9 C2 cardiomyocytes. The sepsisassociated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS(20 mg·kg–1). SFI attenuated the increased expression of tumor necrosis factor(TNF)-α and interleukin(IL)-1β induced by LPS both in serum and heart. In LPS group,cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase(p-MEK) and phosphorylated extracellular regulated protein kinases(p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways. | CHEN Rui-Juan RUI Qing-Lin WANG Qiong TIAN Fang WU Jian KONG Xiang-Qing | 2020 | Chinese Journal of Natural Medicines2020，18，3： | 12 |
| 5 | 法舒地尔临床应用的研究进展显示文摘法舒地尔是一种Rho激酶(Rho-associated kinases,ROCK)抑制剂,是日本旭化成株式会社和名古屋大学药理学研究室合作开发的一种新型异喹啉磺胺衍生物。做为一种新型、高效的血管扩张药,法舒地尔可以有效缓解脑血管痉挛,改善蛛网膜下隙出血(SAH)患者的预后,并取得了大量成果。现进行综述如下。 | 张琳 张骅 | 2011 | 临床肺科杂志2011，16，4： | 11 |
| 6 | Cyclin B1在细胞周期调控及肿瘤发生发展中的作用显示文摘 | 秦丽莉 樊飞跃 詹启敏 | 2008 | 医学研究杂志2008，37，1： | 9 |
| 7 | Inhibition of pacemaker activity in interstitial cells of Cajal by LPS via NF-κB and MAP kinase显示文摘AIM:To investigate lipopolysaccharide(LPS) related signal transduction in interstitial cells of Cajal(ICCs) from mouse small intestine.METHODS:For this study,primary culture of ICCs was prepared from the small intestine of the mouse.LPS was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp technique.Immunocytochemistry was used to examine the expression of the proteins in ICCs.RESULTS:LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809,a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-Larginine Methyl Ester,an inhibitor of nitric oxide(NO) synthase.Toll-like receptor 4,inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ICCs.Catalase(antioxidant agent) had no action on LPS-induced action in ICCs.LPS actions were blocked by nuclear factor kB(NF-kB) inhibitor,actinomycin D(a gene transcription inhibitor),PD 98059(a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases(MAPK) inhibitor].SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not NO.CONCLUSION:LPS inhibit the pacemaker currents in ICCs via prostaglandin E2-and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-kB are implicated in these actions. | Dong Chuan Zuo Seok Choi Pawan Kumar Shahi Man Yoo Kim Chan Guk Park Young Dae Kim Jun Lee In Yeoup Chang Insuk So Jae Yeoul Jun | 2013 | World Journal of Gastroenterology2013，19，8： | 9 |
| 8 | A LysM Receptor Heteromer Mediates Perception of Arbuscular Mycorrhizal Symbiotic Signal in Rice显示文摘Symbiotic microorganisms improve nutrient uptake by plants.To initiate mutualistic symbiosis with arbus-cular mycorrhizal(AM)fungi,plants perceive Myc factors,including lipochitooligosaccharides(LCOs)and short-chain chitooligosaccharides(CO4/CO5),secreted by AM fungi.However,the molecular mechanism of Myc factor perception remains elusive.In this study,we identified a heteromer of LysM receptor-like kinases consisting of OsMYR1/OsLYK2 and OsCERK1 that mediates the perception of AM fungi in rice.CO4 directly binds to OsMYR1,promoting the dimerization and phosphorylation of this receptor complex.Compared with control plants,Osmyr1 and Oscerk1 mutant rice plants are less sensitive to Myc factors and show decreased AM colonization.We engineered transgenic rice by expressing chimeric receptors that respectively replaced the ectodomains of OsMYR1 and OsCERK1 with those from the homologous Nod factor receptors MtNFP and MtL YK3 of Medicago truncatula.Transgenic plants displayed increased cal-cium oscillations in response to Nod factors compared with control rice.Our study provides significant mechanistic insights into AM symbiotic signal perception in rice.Expression of chimeric Nod/Myc recep-tors achieves a potentially important step toward generating cereals that host nitrogen-fixing bacteria. | Jiangman He Chi Zhang Huiling Dai Huan Liu Xiaowei Zhang Jun Yang Xi Chen Yayun Zhu Dapeng Wang Xiaofeng Qi Weichao Li Zhihui Wang Guoyong An Nan YU Zuhua He Yong-Fei Wang Youli Xiao Peng Zhang Ertao Wang | 2019 | Molecular Plant2019，12，12： | 9 |
| 9 | Efficacy of Lubeikangru formulation in mice with hyperplasia of the mammary glands induced by estrogen and progesterone显示文摘OBJECTIVE: To evaluate the protective effects of Lubeikangru formula(LF) on hyperplasia of the mammary glands(HMG) induced by estrogen and progesterone in mice.METHODS: Female mice were divided randomly into five groups: normal, model, tamoxifen(3 mg/kg),Rupixiao(900 mg/kg) and LF(900 mg/kg). All mice except those in the normal group were treated sequentially with estradiol and progesterone to induce HMG. From the tenth day of induction, mice in normal and model groups received distilled water and mice in the other groups were given the corresponding drugs by gavage, once a day, for 30 d.At the end of treatment, the mammary glands, ovaries, hypothalamus, and serum was collected for whole-mount and hematoxylin and eosin(HE)staining, enzyme-linked immunosorbent assays(ELISAs), or western blotting.RESULTS: Whole-mount and HE staining of mammary glands showed that LF rescued(at least in part) the hyperplasic morphology of the mammary glands, and the number of branch points decreased after LF treatment(P < 0.05). ELISAs revealed that levels of estrogen and progesterone were decreased following LF treatment, whereas levels of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone were increased in serum and tissues. Western blotting confirmed that LF treatment led to a reduction in expression of phosphorylated(p)-Erk, p-p38 and p-c-Jun N-terminal kinase. LF was also confirmed to be safe by acute-toxicity tests.CONCLUSION: LF can protect the mammary glands of mice from estrogen-and progesterone-induced hyperplasia by adjusting hormone levels and regulating the mitogen-activated protein kinase pathway. | Sun Li Guo Donghui Liu Qian Xue Yanan Jiang Ning Zheng Hongxin | 2019 | Journal of Traditional Chinese Medicine2019，39，2： | 8 |
| 10 | Extracts from Huangqi(Radix Astragali Mongoliciplus) and Ezhu(Rhizoma Curcumae Phaeocaulis) inhibit Lewis lung carcinoma cell growth in a xenograft mouse model by impairing mitogen-activated protein kinase signaling, vascular endothelial growth factor prod显示文摘OBJECTIVE: To study the anti-tumor effects of the extracts from Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis) on the growth of Lewis lung carcinoma(LLC) in a xenograft mouse model and to investigate the possible underlying mechanism.METHODS: LLC tumor-bearing C57 BL/6 mice were treated with normal saline, cisplatin(2 mg/kg intraperitoneally every other day), or Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis)(1∶1, 2∶1, or 3∶1 ratio;5, 8, or 11 g/kg crude drug intragastrically every day) for 15 d.Body weights and tumor volumes were measured every other day. Tumors were excised on day 15 and analyzed. Tumor microvessel density(MVD)was assessed by immunohistochemical staining of CD34;and expression of vascular endothelial cell growth factor(VEGF), the mitogen-activated protein kinases p38 mitogen-activated protein kinase(MAPK), extracellular signal-regulated kinases 1 and 2(ERK1/2), and Jun N-terminal kinase(JNK)and their phosphorylated forms were assessed by Western blotting.RESULTS: Treatment with cisplatin caused a significant loss of body weight compared with controls,whereas Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) extract combinations had no effect. Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) significantly decreased tumor weight and tumor MVD compared with controls,and at the 3∶1 treatment group had similar efficacy to cisplatin in reducing MVD. Tumors from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) treatments also showed decreased p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2,JNK, and p-JNK expression compared with the control group(all P < 0.01). VEGF protein expression was significantly reduced in the 2∶1 and 3∶1 treatment groups compared with the control group(P < 0.01).CONCLUSION: Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) hindered LLC growth in the xenograft mouse model, possibly via inhibition of the MAPK signaling pathway, VEGF production, and tumor angiogenesis. | Xu Chengyong Wang Yuguo Feng Jian Xu Ran Dou Yongqi | 2019 | Journal of Traditional Chinese Medicine2019，39，4： | 7 |
| 11 | p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation显示文摘Pancreatic cancer is one of the most aggressive and lethal malignancies worldwide, with a very poor prognosis and a five-year survival rate less than 8%. This dismal outcome is largely due to delayed diagnosis, early distant dissemination and resistance to conventional chemotherapies. Kras mutation is a well-defined hallmark of pancreatic cancer, with over 95% of cases harbouring Kras mutations that give rise to constitutively active forms of Kras. As important down-stream effectors of Kras, p21-activated kinases(PAKs) are involved in regulating cell proliferation, apoptosis, invasion/migration and chemo-resistance. Immunotherapy is now emerging as a promising treatment modality in the era of personalized anti-cancer therapeutics. In this review, basic knowledge of PAK structure and regulation is briefly summarised and the pivotal role of PAKs in Kras-driven pancreatic cancer is highlighted in terms of tumour biology and chemoresistance. Finally, the involvement of PAKs in immune modulation in the tumour microenvironment is discussed and the potential advantages of targeting PAKs are explored. | Kai Wang Graham S Baldwin Mehrdad Nikfarjam Hong He | 2018 | World Journal of Gastroenterology2018，24，33： | 7 |
| 12 | 盘状结构域受体研究进展显示文摘盘状结构域受体(diScoidin domain receptors,DDRs)是一类受体型蛋白酪氨酸激酶(protein tyrosine kinases,RTKs),属于非整合型胶愿受体家族。目前发现该家族包含两个成员:DDR1和DDR2。DDRs参与了细胞的黏附、增殖及细胞外基质的重塑,在人体多种病理生理过程中起到重要作用。以下就近几年关于DDRs的结构特点、功能及其在人类多种疾病中作用的最新进展做一综述。 | 郭晓娟 胡永红 | 2009 | 中华风湿病学杂志2009，13，2： | 5 |
| 13 | Targeting receptor tyrosine kinases in gastric cancer显示文摘Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials.One group of representative targeted oncogenic kinases,the receptor tyrosine kinases(RTKs),has been associated with gastric cancer development.Trastuzumab,an inhibitor of ERBB2,has been approved for the treatment of gastric cancer,although other receptor tyrosine kinases,such as epidermal growth factor receptor,vascular endothelial growth factor,platelet-derived growth factor receptor,c-Met,IGF-1R and fibroblast growth factor receptor 2,are also activated in gastric cancer.The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients.On the other hand,the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients;however,a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial.Other clinical trials,especially phaseⅢtrials that have tested drugs targeting RTKs,such as cetuximab,panitumumab,gefitinib,erlotinib,figitumumab,sorafenib,sunitinib and lapatinib,have shown that these drugs have modest effects against gastric cancer.This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies. | Asahiro Morishita Jian Gong Tsutomu Masaki | 2014 | World Journal of Gastroenterology2014，20，16： | 5 |
| 14 | Efficacy of Zhonglun'a-decoction-containing serum on fibroblastlike synoviocyte apoptosis in rats with collagen-induced arthritis via inhibiting Janus kinase/signal transducer and activator of transcription signaling pathway显示文摘OBJECTIVE: To investigate the efficacy of Zhonglun'a-decoction-containing serum(ZHONGL-CS)on the in vitro apoptosis of fibroblast-like synoviocytes(FLS) from rats with collagen-induced arthritis(CIA) by investigating the Janus kinase/signal transducer and activator of transcription(JAK/STAT) signaling pathway.METHODS: A CIA rat model was established using bovine type Ⅱ collagen. FLS were isolated, cultured and identified. A cell counting kit-8 was used to detect cell activity. The half maximal inhibitory concentration(IC50) was calculated. Experimental subjects were divided into control, CIA,ZHONGL-CS, JAK2 inhibitor AG490, and ZHONGLCS with AG490 groups. The in vitro cell cycle and apoptosis rate were detected in FLS by flow cytometry. Bcl-2-associated X protein(Bax), B-cell lymphoma 2(Bcl-2), caspase-3, cyclin D1, phosphorylated JAK2, STAT1, and STAT3 protein expressions in FLS were examined by Western blotting. JAK2, STAT1 and STAT3 mRNA levels were examined by quantitative real-time polymerase chain reaction.RESULTS: Compared with the CIA group, FLS proliferation was inhibited, the FLS G0/G1 cell cycle was arrested, and the rate of FLS apoptosis was increased in the ZHONGL-CS group. In the ZHONGLCS group, the protein levels of Bcl-2 and cyclin D1 were reduced compared with the CIA group and the levels of Bax and caspase-3 in FLS were increased. In the ZHONGL-CS group, the expressions of JAK2, STAT1, and STAT3 mRNA and the levels of phosphorylated JAK2, STAT1, and STAT3 proteins were reduced.CONCLUSION: ZHONGL-CS may induce FLS apoptosis in CIA rats. Activation of the JAK/STAT signaling pathway was inhibited in FLS in vitro. | Yang Yongsheng Dong Qiumei Ma Chunjie Zhang Yudi Li Yongle Chen Kun Zhang Suo | 2019 | Journal of Traditional Chinese Medicine2019，39，2： | 4 |
| 15 | Protein phosphorylation is involved in the water stress-induced ABA accumulation in the roots of Malus hupehensis Rehd显示文摘Water stress-induced ABA accumulation plays a key role in the root to shoot communication and/or the cell to cell signaling under the soil stresses. The signaling of the water stress itself that leads to the accumulation, however, is less known. In this study, we subjected the roots of Malus hupehensis seedlings to water stress treatment and investigated the ABA accumulation in relation to protein phos-phorylation. Our results showed that ABA accumulation could be substantially triggered in 40 min and reached 4 folds in 100 min after treatment with 30% PEG 6000 (polyethylene glycol). The water stress treatment also led to a substantial enhancement of total kinase activity, assessed with histone-111 as substrate, in 15 min and a maximum enhancement in 30 min before it declined to initial level. The Ca2+-dependent kinase activity showed a similar, if not more sensitive, trend. When the roots were fed with labeled 32P-ATP, water stress enhanced the labeling of proteins, which showed a maximum labeling at | ZHANG Dapeng, YANG Hongqiang, JIA Wensuo & HUANG Conglin1. Laboratory of Molecular Developmental Biology of Fruit Trees, China Agricultural University, Beijing 100094, China 2. The Key Laboratory of Plant Physiology and Biochemistry of Agricultural Ministry, China Agricultural University, Beijing 100094, China | 2001 | Chinese Science Bulletin2001，46，10： | 4 |
| 16 | Research progress on signaling pathways in cirrhotic portal hypertension显示文摘Portal hypertension(PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient's quality of life and survival, such as upper gastrointestinal bleeding, ascites, and portosystemic encephalopathy. In recent years, advances in molecular biology have led to major discoveries in the pathological processes of PHT, including the signaling pathways that may be involved: PI3 K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and farnesoid X receptor. However, the pathogenesis of PHT is complex and there are numerous pathways involved. Therefore, the targeting of signaling pathways for medical management is lagging. This article summarizes the progress that has been made in understanding the signaling pathways in PHT, and provides ideas for treatment of the disorder. | Wen Xu Ping Liu Yong-Ping Mu | 2018 | World Journal of Clinical Cases2018，6，10： | 3 |
| 17 | 载脂蛋白E对细胞因子表达的免疫调节作用显示文摘载脂蛋白E(ApoE)是一种重要的血浆脂蛋白,除调节脂质代谢,在体外能够抑制T淋巴细胞的增殖。近来研究发现ApoE还参与核因子-κB(NF-κB)和促分裂素原活化蛋白激酶(mitogenactivated protein kinases,MAPK)等细胞内多种信号转导,通过对细胞因子表达的调节发挥抗炎和免疫调节作用。本文从ApoE对白细胞介素、干扰素、肿瘤坏死因子、趋化因子等细胞因子的调节作用方面做一概述。 | 殷丽军 王传清 | 2011 | 中华微生物学和免疫学杂志2011，31，6： | 2 |
| 18 | TrkA regulates the regenerative capacity of bone marrow stromal stem cells in nerve grafts显示文摘We previously demonstrated that overexpression of tropomyosin receptor kinase A(TrkA)promotes the survival and Schwann celllike differentiation of bone marrow stromal stem cells in nerve grafts,thereby enhancing the regeneration and functional recovery of the peripheral nerve.In the present study,we investigated the molecular mechanisms underlying the neuroprotective effects of TrkA in bone marrow stromal stem cells seeded into nerve grafts.Bone marrow stromal stem cells from Sprague-Dawley rats were infected with recombinant lentivirus vector expressing rat TrkA,TrkA-shRNA or the respective control.The cells were then seeded into allogeneic rat acellular nerve allografts for bridging a 1-cm right sciatic nerve defect.Then,8 weeks after surgery,hematoxylin and eosin staining showed that compared with the control groups,the cells and fibers in the TrkA overexpressing group were more densely and uniformly arranged,whereas they were relatively sparse and arranged in a disordered manner in the TrkA-shRNA group.Western blot assay showed that compared with the control groups,the TrkA overexpressing group had higher expression of the myelin marker,myelin basic protein and the axonal marker neurofilament 200.The TrkA overexpressing group also had higher levels of various signaling molecules,including TrkA,pTrkA(Tyr490),extracellular signal-regulated kinases 1/2(Erkl/2),pErk1/2(Thr202/Tyr204),and the anti-apoptotic proteins Bcl-2 and Bcl-xL.In contrast,these proteins were downregulated,while the pro-apoptotic factors Bax and Bad were upregulated,in the TrkA-shRNA group.The levels of the TrkA effectors Akt and pAkt(Ser473)were not different among the groups.These results suggest that TrkA enhances the survival and regenerative capacity of bone marrow stromal stem cells through upregulation of the Erk/Bcl-2 pathway.All procedures were approved by the Animal Ethical and Welfare Committee of Shenzhen University,China in December 2014(approval No.AEWC-2014-001219). | Mei-Ge Zheng Wen-Yuan Sui Zhen-Dan He Yan Liu Yu-Lin Huang Shu-Hua Mu Xin-Zhong Xu Ji-Sen Zhang Jun-Le Qu Jian Zhang Dong Wang | 2019 | Neural Regeneration Research2019，14，10： | 2 |
| 19 | “Stop Ne(c)king around”: How interactomics contributes to functionally characterize Nek family kinases显示文摘Aside from Polo and Aurora, a third but less studied kinase family involved in mitosis regulation is the never in mitosis-gene A(NIMA)-related kinases(Neks). The founding member of this family is the sole member NIMA of Aspergillus nidulans, which is crucial for the initiation of mitosis in that organism. All 11 human Neks have been functionally assigned to one of the three core functions established for this family in mammals:(1) centrioles/mitosis;(2) primary ciliary function/ciliopathies; and(3) DNA damage response(DDR). Recent findings, especially on Nek 1 and 8, showed however, that several Neks participate in parallel in at least two of these contexts: primary ciliary function and DDR. In the core section of this in-depth review, we report the current detailed functional knowledge on each of the 11 Neks. In the discussion, we return to the cross-connections among Neks and point out how our and other groups' functional and interactomics studies revealed that most Neks interact with protein partners associated with two if not all three of the functional contexts. We then raise the hypothesis that Neks may be the connecting regulatory elements that allow the cell to fine tune and synchronize the cellular events associated with these three core functions. The new and exciting findings on the Nek family open new perspectives and should allow the Neks to finally claim the attention they deserve in the field of kinases and cell cycle biology. | Gabriela Vaz Meirelles Arina Marina Perez Edmárcia Elisa de Souza Ferna Luisa Basei Priscila Ferreira Papa Talita Diniz Melo Hanchuk Vanessa Bomfim Cardoso Jrg Kobarg | 2014 | World Journal of Biological Chemistry2014，5，2： | 2 |
| 20 | Group Ⅱ p21-activated kinases as therapeutic targets in gastrointestinal cancer显示文摘P21-activated kinases(PAKs) are central players in various oncogenic signaling pathways. The six PAK family members are classified into group Ⅰ(PAK1-3) and group Ⅱ(PAK4-6). Focus is currently shifting from group Ⅰ PAKs to group Ⅱ PAKs. Group Ⅱ PAKs play important roles in many fundamental cellular processes, some of which have particular significance in the development and progression of cancer. Because of their important functions, group Ⅱ PAKs have become popular potential drug target candidates. However, few group Ⅱ PAKs inhibitors have been reported, and most do not exhibit satisfactory kinase selectivity and 'drug-like' properties. Isoform- and kinase-selective PAK inhibitors remain to be developed. This review describes the biological activities of group Ⅱ PAKs, the importance of group Ⅱ PAKs in the development and progression of gastrointestinal cancer, and smallmolecule inhibitors of group Ⅱ PAKs for the treatment of cancer. | Yang-Guang Shao Ke Ning Feng Li | 2016 | World Journal of Gastroenterology2016，22，3： | 2 |
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