1.Acute myeloid leukemia treatment in the elderly patients
Journal of Leukemia & Lymphoma 2009;18(6):379-382
The outcome of the elderly patients with acute myeloid leukemia (AML) has not improved in the last three decades. Their clinical features limit the ability to tolerate intensive cytotoxic chemotherapy and result in greater early mortality. The AML seen in elderly patients is also more likely to have greater resistance to therapy. Attempts to improve outcome have generally been unsuccessful But further manipulation of standard cytotoxic chemotherapy alone is unlikely to improve the outcome for the majority of patients with AML.
2.Noncoding RNA in research of pharmacology
Chinese Journal of Pharmacology and Toxicology 2016;30(12):1282-1289
Discovery of noncoding RNA(ncRNA)over the past decade has reflected a paradigm shift of traditional RNA research. There is evidence that RNA can function not only as a messenger between DNA and protein,but as a regulator of genome organization and gene expression,which is increasingly elaborate in complex organisms. ncRNA seems to operate at many levels,however,in?cluding the physiological and pathological status. The research of ncRNA in pharmacology has not been summarized before. Here,we reviewed the emergence of the ncRNA in the research of pharma? cology,such as acting as biomarkers and medical targets. Besides,we mentioned their role in drug resistance and drug addiction in order to highlight the significant role of ncRNA in pharmacology.
3.Biological functions and drug development of Pyk2
Zhao ZHANG ; Shifeng CHU ; Naihong CHEN
Chinese Pharmacological Bulletin 2014;(6):744-747,748
Pyk2(Proline-rich tyrosine kinase 2) is an important member of focal adhesion kinase family. Pyk2 is highly ex-pressed in the central nervous system and the hematopoietic sys-tem . Pyk 2 can trigger a variety of SH 2 domain-containing pro-
teins to phosphorylate their substrates, thus it can participate in the regulations including ion channel activation, stress response, cell adhesion, cytoskeleton reorganization, vesicle transport and so on. Through the regulations above, the ability of cell migra-tion, survival, proliferation changes accordingly, suggesting that Pyk2 in many important regulatory processes may become a tar-get for clinical effects. Current drug development for Pyk2 main-
ly focuses on cancer, osteoporosis and immune response. This review illustrates the domain structure, regulatory mechanisms, potential drug targets, and the drug development of Pyk2 based on the above three fields, which will provide a theoretical basis for clinical treatment.
4.Some diseases caused by Parkin
Yina JIANG ; Yuxia LOU ; Zhao ZHANG ; Naihong CHEN
Chinese Pharmacological Bulletin 2016;32(4):455-458
Since Parkin was confirmed by the Japanese scholar to be associated with juvenile Parkinson′s disease, it has come to be the focus of the scholars and a lot of researches have been made on it. Apart from Parkinson′s disease, many other disea-ses have also been proved to be associated with the role of Parkin and its interaction with protein substrates, especially in various kinds of cancer diseases and leukemia. This paper focuses on the latest research about Parkin and its development in tumor diseases and leukemia.
5.Inhibitory Effect of (-)Clausenamide on Apoptosis of PC12 Cells Induced by Serum Deprivation and Its Related Mechanism
Jinfeng HU ; Na NING ; Wei XUE ; Juntian ZHANG ; Naihong CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 1993;0(01):-
Objective To study the protective effect of(-)clausenamide on the damage of PC12 cells induced by serum deprivation and to explore its related mechanism. Methods The cell viability was detected by MTT assay and morphological observation. The effect of(-)clausenamide on the PC12 cell apoptosis was analyzed by flow cytometry. Then western blotting and confocal microscope was used for the further study of effect of(-)clausenamide on the protein expression of GSK-3?,Bax and Bcl-2. Results(-)Clausenamide remarkably increased PC12 cell survival rate through inhibiting the PC12 cell apoptosis induced by serum deprivation at the concentration of 1 or 10 ? mol/L(P
6.CKLF1 induces SH-SY5 Y cell migration via PLCγ/FAK signaling pathway
Zhenzhen WANG ; Yuhe YUAN ; Ning HAN ; Yi ZHANG ; Naihong CHEN
Chinese Pharmacological Bulletin 2014;(9):1209-1213
Aim To investigate the role of chemokine-like factor 1 ( CKLF1 ) in SH-SY5 Y cell migration and its molecular regulatory mechanism. Methods SH-SY5Y cells were stimulated with CKLF1 for 0. 5 h, 2 h, 8 h and 24 h, respectively. The migration distance and the percentage of migration cells were recorded by CELLocate analysis. The phosphorylation of focal ad-hesion kinase ( FAK) at Tyr-397 site was detected by Western blot analysis. By chemotaxis assays, we con-firmed the chemotaxis of CKLF1. Furthermore, FAK inhibitor PF-573228 and PLCγ inhibitor U73122 were used for the research of molecular regulatory mecha-nisms involved. Results CKLF1 promoted cell migra-tion and induced a strong increase in the phosphoryla-tion level of FAK-pY397 , which were significantly at-tenuated by the presence of U73122 ( a specific inhibi-tor for PLCγ) . In addition, the chemotaxis of CKLF1 was obviously blocked by the FAK inhibitor PF-573228 . Conclusion CKLF1 induces SH-SY5 Y cell migration via PLCγ/FAK signaling pathway.
7.Effect of (-)clausenamide on potentiating synaptic transmission in dentate gyrus:Role of synapsin Ⅰ
Jinfeng HU ; Na NING ; Yuhe YUAN ; Juntian ZHANG ; Naihong CHEN
Chinese Pharmacological Bulletin 1986;0(05):-
Aim To study the effect of synapsinⅠon synaptic transmission in rat dentate gyrus induced by(-) clausenamide.Methods The basal synaptic transmission experiment was conducted through electrophysiological recordings.The effect of(-) clausenamide on synapsinⅠ phosphorylation was measured by western blot and confocal microscopy.Results(-)Clausenamide increased the population spike(PS) of hippocampal dentate gyrus.The phosphorylation of synapsinⅠ was increased both in cortex and hippocampus,the maximum effect was observed at 5 min in hippocampus and at 15 min in cortex.Furthermore,(-)clausenamide promoted the phosphorylation of synapsinⅠat a dose-denpendent manner in PC12 cells.The phosphorylation of synapsinⅠ in PC12 cells and synaptosomes incubated with(-)clausenamide was increased and reached maximum at 1~2 min.However,H89,PKA inhibitor,blocked the effect of(-)clausenamide on synapsinⅠ phosphorylation.Conclusion(-)Clausenamide activated synapsinⅠ via PKA signal pathway,which may contribute to the effect of(-)clausenamide on potentiating basal synaptic transmission.
8.CaMKⅡ:A molecular switch of synaptic plasticity
Wenbin HE ; Junlong ZHANG ; Longchuan YU ; Naihong CHEN
Chinese Pharmacological Bulletin 2014;(7):897-900,901
Calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ),which is an important protein kinase involved in learning and memory,is found in most tissues,but it is present in especially high concentrations in neurons.The relatively high expression of CaMKⅡin nervous system suggests it plays an im-portant role in the function of nervous system.This paper re-views the research development of the molecular structure of CaMKⅡ and its autophosphorylation,subcellular localization and its role in synaptic plasticity.
9.Study of synergistic effect of hyperlipoproteinemiaand Aβ in processing of Alzheimer′s disease
Jiangqi HOU ; Xin ZHANG ; Qin LONG ; Shifeng CHU ; Lei GUO ; Wenbin HE ; Junlong ZHANG ; Naihong CHEN
Chinese Pharmacological Bulletin 2017;33(4):498-506
Aim To research the synergistic effect of hyperlipoproteinemia and Aβ in the processing of Alzheimer′s disease.Methods Seventy SD rats were randomly divided into seven groups, and dealt with D-gal(hypodermic injection), hyperlipemia diet, microinjection into both side of CA1 section in hippocampus, independently.Morris water maze(MWM) test was used to evaluate the spatial memory impairments.Tau and tau(pThr181) pathology in the hippocampus were detected using Western blot and immunohistochemistry.Nissl′s staining was used to detect cell apoptosis.Results Aβ25-35-treated rats showed significant impairments of spatial memory in MWM test, especially in the group of D-gal+Aβ25-35+HLD(P<0.01).Furthermore, these rats treated with Aβ25-35, D-gal, and hyperlipemia diet, exhibited significantly increased phosphorylation of tau, particularly in the Thr181 site.Conclusion Hyperlipoproteinemia is the risk factor for older person, which could strengthen the toxic effect of Aβ, and promote phosphorylation of tau.
10.IFN-γup-regulates Th17/IL-17 response against Chlamydia trachomatis lung infection
Haiping WANG ; Naihong ZHANG ; Donghong XING ; Xiaofei TANG ; Zhaoe WANG ; Huanjun HUANG ; Hong BAI
Chinese Journal of Microbiology and Immunology 2011;31(1):10-13
Objective To investigate the regulation of IFN-γ to Th17 response in Chlamydia muridarum (Cm) lung infection in mice. Methods A murine model of pneumonia induced by intranasal inoculation of Cm was used for this study. Anti-mouse IFN-γ McAbs were used to neutralize endogenous IFN-γfollowing Cm lung infection. Control group received the same dose of isotype antibody (IgG2a). Mice were sacrificed at day 7 postinfection. Chlamydial growth in the lung was assessed by immunoenzyme technique.IL-17 and IL-23 mRNA expression in the lung was assayed by RT-PCR and the proliferation of IL-17 + CD4 +T cells in the spleen was assayed by intracellular cytokine staining. Results IFN-γ-neutralized mice exhibited serious disease course, include greater body weight loss, higher organism growth and much more severe pathological changes in the lung compared with control mice. The mRNA expression of IL-17 and IL-23 in the lung and the proliferation of IL-17 + CD4 + T cells in the spleen significantly decreased in the IL-17- neutralized mice. Conclusion IFN-γ was protective in Cm lung infection through up-regulating the antigen specific Th17 responses.