1.Mechanism of CCL2/MCP-1 in its relevant diseases
Chinese Pharmacological Bulletin 2016;32(12):1634-1638
Chemokine is a small protein which plays an impor-tant role in men's physiological function.It has chemotactic ac-tivity and is often secreted by immune cells and glial cells like microglia or astrocytes.Through the effect of chemokine recep-tors on target cells,various immune cells can achieve directional migration and play an important role in the diseases related with immunity and inflammation.CCL2,also known as monocyte chemotactic protein-1 (MCP-1 ),is one member of chemokine CC subfamily (βsubfamily).It can chemokine monocytes, macrophages and T lymphocytes to affect their phagocytosis func-tion and produce antibodies to combat invading microorganisms. In recent years,it has been found that CCL2 plays a key role in the occurrence and development of the problems concerning cen-tral nervous system and immune system as well as cancer, AIDS,leukemia,diabetes and other diseases.This thesis is to give an elaboration on the latest research on CCL2 and the rele-vant diseases.
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.Advances in the study of small molecule antagonists of chemokine receptors as anti-asthma agents.
Haijie JI ; Jinfeng HU ; Naihong CHEN
Acta Pharmaceutica Sinica 2011;46(11):1286-90
Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
4.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.
5.Advance in the Mechanism of Anti-platelet Aggregation Drugs (review)
Xiaofeng WANG ; Naihong CHEN ; Wen WANG
Chinese Journal of Rehabilitation Theory and Practice 2010;16(10):954-957
The latest literatures showed that the anti-platelet aggregation drugs had a good application in cardiovascular disease, however still with hemorrhage side effects and some new drugs' mechanism was unknown. So further investigations on the mechanism of anti-platelet aggregation are necessary to discover a new type of anti-platelet drugs, such as antagonists of the EP3 receptor.
6.Effects of Morroniside on Platelet Aggregation in Rabbit
Xiaofeng WANG ; Naihong CHEN ; Wen WANG
Chinese Journal of Rehabilitation Theory and Practice 2010;16(11):1029-1030
ObjectiveTo study the effects of Morroniside on platelet aggregation in rabbits induced by Adenosine diphosphate (ADP), Arachidonic acid (AA), Platelet activating factor (PAF). MethodsThe platelet aggregation was determined by Born's method. ResultsCompared with the controls, Morroniside inhibited platelet aggregation induced by ADP, AA, PAF (P<0.001)and especially selective on ADP. ConclusionMorroniside inhibited platelet aggregation in rabbits, especially induced by ADP.
7.Increased protein level of α-synuclein in the midbrain of Parkinson's disease rat model
Jiandong SUN ; Yuhe YUAN ; Yan LIU ; Xiaofeng WANG ; Naihong CHEN
Chinese Pharmacological Bulletin 2010;26(1):73-77
Abstract:Aim To study the effect of rotenone on α-synuclein in rat midbrain of Parkinson's disease(PD).Methods Rats were subcutaneouly injected with chronic low dose rotenone(1.0 mg·kg~(-1)·d~(-1)).Movements within 5 minutes were evaluated in open field test.Tyrosine hydroxylase(TH)-positive neuronsin the midbrain were measured with immunofluorescence staining.α-SYN protein level in the midbrain was demonstrated with immunohistochemical staining and Western blot.Results Compared to the control group,latency time,crossing,rearing and rearing time were changed significantly(P<0.05,0.01)in the rotenone group,TH-positive neurons were reduced(P<0.05)and α-SYN protein level in the midbrain was increased(P<0.05).Conclusion Injection with rotenone can induce PD symptom,which may be correlated to α-SYN protein level in the midbrain.
8.Construction of cell model targeted on the damage by α-synuclein
Wenfen YAN ; Yang HENG ; Qianhang SHAO ; Naihong CHEN ; Yuhe YUAN
Chinese Pharmacological Bulletin 2015;(4):586-590
Aim To construct the cell model targeted on the damage by α-synuclein for screening anti-Parkinson’s Disease (PD)compounds.Methods The cDNA fragment of α-synucle-in gene was obtained by PCR methods and inserted into the re-combinant prokaryotic plasmid by molecular cloning technique. The recombinant plasmid was transformed into Escherichia coli, and subsequently induced to express α-synuclein protein.The recombinant α-synuclein was purified and identified by affinity chromatography,immunoblotting and mass spectrometry.The cells damage by α-synuclein was evaluated through cell viability measured by 3-(4,5-dimethyl-2-thiazolyl )-2,5-diphenyl-2-H-tetrazolium bromide.Results The obtained cDNA fragment ofα-synuclein in accordance with its theoretic molecular weight was cloned into pET30a plasmid and verified by sequencing.The re-combinant plasmid was transformed into bacteria E.Coli.BL21 (DE3)and induced to express α-synuclein by isopropyl β-D-1 -thiogalactopyranoside (IPTG).The expression condition was op-timized according to the culture temperature,the concentration of IPTG and the proliferation state of bacteria.The purified α-synu-clein was proved to be a 1 5.3 ku molecule weight protein,and could be immunoblotted with anti-α-synuclein antibody.The pu-rified α-synuclein could decrease the viability of PC1 2 cells and primary neurons significantly,and its effect was in a concentra-tion-dependent manner.Conclusion We have succeeded in constructing the cell model targeted on the damage by α-synucle-in.
9.Mifepristone repairs alteration of learning and memory abilities in rat model of depression.
Jing LI ; Jiandong SUN ; Yan LIU ; Yuhe YUAN ; Naihong CHEN
Acta Pharmaceutica Sinica 2013;48(8):1221-6
This study is to investigate the amelioration effect of glucocorticoid receptor (GR) antagonist mifepristone on the changes of learning and memory abilities in rat model of depression. In the present study, a 35-day rat chronic unpredictable stress (CUS) model was used to observe both depression-like behaviors with sucrose preference test and open-field test and learning and memory-associated behaviors with Morris water maze test. A total of 45 male adult Sprague-Dawley rats were randomly assigned to three groups of equal size: control group (CON); CUS group (CUS); CUS + mifepristone group (CM). Animals in CM group were first exposed to CUS for 14 days, and then were administered with 50 mg x kg(-1) x d(-1) of mifepristone with continued CUS procedure. Corticosterone EIA Kit was used to detect the concentration of plasma corticosterone (CORT). Nissl staining was used to observe the structure of hippocampus. The results demonstrated that CUS exposure induced both depressive-like and learning and memory-associated behaviors and these deficits were reversed by mifepristone. Compared to CON group, the concentration of plasma CORT increased significantly in CUS group. CUS exposure damaged the structure of hippocampus, whereas mifepristone had an amelioration effect. Together, the structural deficits of hippocampus resulting from long-term stress exposure, which could contribute to the impairment of learning and memory in depression, are reversed by the GR receptor antagonist mifepristone.
10.Establishing the Rat Model of Multi-infarct Dementia
Donghui WU ; Jinfeng HU ; Zhipeng LI ; Haijie JI ; Naihong CHEN
Chinese Journal of Rehabilitation Theory and Practice 2011;17(3):232-234
ObjectiveTo establish the rat model of multi-infarct dementia. MethodsSephadex (4 mg/ml, 8 mg/ml) was injected into the internal carotid artery through the common carotid artery. Neurological deficits were measured 24 h after the operation, and Morris water maze test as well as Nissl stain were observed 26~30 d after the operation. ResultsThere was significant difference between the model groups injected sephadex of 8 ml/ml and 4 mg/ml in the neurologic deficits. In the following experiment, the rats injected sephadex of 8 mg/ml were only used as model. For the water maze test, the escape latency was longer (P<0.01) and the frequency across target area reduced (P<0.01) in the model, while the apoptotic Nissl body could be observed. ConclusionA model of multi-infarct dementia could be established with the sephadex in rats.