1.The mTORC1 signaling network underlying the pathogenesis and treatment of depression:new insights into rapid-acting antidepressant therapies
Ting ZENG ; Zhen-Zhen WANG ; Nai-Hong CHEN
Chinese Journal of Pharmacology and Toxicology 2018;32(4):331-331
Depression is a devastating mental disorder and major depressive disorder (MDD) that afflicts 16% of the global population at some point in their lives. Currently available classical antide-pressants (SSRIs, SNRIs, TCAs and MOIs), require a minimum of 2–4 weeks of continuous treat-ment to elicit therapeutic relief in depressed patients and are associated with high rates of non-respon-siveness, and limited duration of efficacy. Therefore, faster-acting antidepressant therapies are need-ed,particularly for patients at risk for suicide for current therapies for depression.Although the molecu-lar mechanisms underlying the pathogenesis of depression are still largely unclear, previous studies have suggested that modulators of mammalian target of rapamycin complex 1 (mTORC1) signaling may have beneficial neuroprotective and antidepressant effects. Here, we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling network. We also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy (e.g. ketamine, scopolamine, GLYX-13, (2R,6R)-HNK, Ro-256891 etc.) and discuss future research directions. Studies on prospec-tive next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs) agonists or activators)that activate the mTORC1 signaling pathway free of ketamine's adverse effects.
2.Association of depression with dietary fatty acids and the progress of mechanism research
Ning-ning ZHANG ; Zhen-zhen WANG ; Nai-hong CHEN
Acta Pharmaceutica Sinica 2021;56(4):906-912
Depression is one of the diseases with the highest disability rate in the world. A large number of studies have shown that the intake of unsaturated fatty acids can deal with depression while chronic overconsumption of saturated fatty acids is a risk factor for depression. It was suggested that the mechanism of saturated fatty acids inducing depression is related to the following four aspects: regulating the function which links to depression in whole brain and specific brain regions, including the hippocampus, the hypothalamic-pituitary-adrenal axis, the striatum, and the prefrontal cortex; stimulating the secretion of inflammatory factors; affecting the balance and function of metabolic regulatory hormones, including leptin, adiponectin, glucocorticoid, and insulin; inducing the disturbance of intestinal flora. This article reviews the relationship between dietary fatty acids and depression, and the possible mechanisms by which saturated fatty acids induce depression from the four aspects mentioned above.
3.Design of Control System of Charge Evasion in Medical Equipment Based on Embedded System
Zhen LIU ; Hong WANG ; Jinan LIN
Chinese Medical Equipment Journal 2009;30(7):54-56
Obiective To solve the problem of charge evasion in medical equipment and improve the management of medical equipment and increase income of the hospital.Methods The control system was designed and used based onembedded system as real-time monitor in the medical equipment. Results This system can realize the real-time monitor of the medical equipment and improve the management of hospital. Conclusion The system resolves the problem of charge evasion effectually and increases the income of the hospital.
4.Studies on the etiologies and classification of uveitis
Peizeng YANG ; Zhen ZHANG ; Hong WANG
Chinese Journal of Ocular Fundus Diseases 2000;0(04):-
Objective To study the clinical classification and etiologies of uveitis based on 1 214 uveitis patients reffered to Zhongshan Ophthalmic Center. Methods A retrospective analysis was made on the patients with uveitis, coming from all over China between January 1996 and December 2001. All kinds of uveitis were classified according to the anatomical criteria and etiological criteria. The relevant data of these patients, such as the age at uveitis onset and sex were also analyzed. Results The total number of the patients is 1 214 (male 698, female 516), with the average age at disease onset being 34.43. Anterior uveitis, the most common type, was seen in 546 cases, accounting for 44.98% of all the patients, followed in descending order by panuveitis (530 cases, 43.66%), intermediate uveitis(78 cases, 6.43%) and posterior uveitis(60 cases, 4.94%). Etiological factors and clinical entities were identified in 703 patients, accounting for 57.91% of all the patients, and the other 511 patients were idiopathic ones. The most common types of anterior uveitis were idiopathic uveitis(316 cases, 57.88%), followed by Fuchs syndrome(85 cases) and ankylosing spondylitis(45 cases). Behcet ) disease(218 cases, 41.13%) and Vogt-Koyanagi-Harada syndrome(196 cases, 36.98%) were the most common entities in panuveitis. Neither etiological factors nor clinical entities could be identified in the patients with intermediate uveitis and those with posterior uveitis. Conclusions Uveitis occurs mostly in young and middle-aged adults. In general, a predilection was seen in the male as compared with the female in the development of uveitis. Idiopathic anterior uveitis, Behcet ) disease and Vogt-Koyanagi-Harada syndrome are the most common entities of uveitis seen in China. Classification based on etiological and anatomical factors may provide a reasonable system for the study of uveitis.
5.Expression of costimulatory molecules on peripheral blood lymphocytes in patients with Behet's disease
Hong WANG ; Peizeng YANG ; Zhen ZHANG
Chinese Journal of Ocular Fundus Diseases 2003;0(06):-
Objective To investigate the expression of costimulatory molecules( B7, CD28, and CTLA-4) of peripheral blood lymphocytes in patients with Behcet′s ) disease(BD). Methods Lymphocytes were obtained in 24 patients with BD and 20 healthy individuals, and the expression of CD80(B7-1), CD86(B7-2), CD28 and CTLA-4 on T and B cells were detected by direct three-color immunofluorescence flow cytometry. Results Significantly increased expression of CTLA-4 on CD4 + T cells [(3. 18?1. 18)%] was found in BD patients compared with that in controls [(1. 73?0. 66) %] ( t=-3. 722,P
6.A Cross-sectional Survey on Risk Factors of Stroke in Sampling Population Aged over 40 Years among Communities in Four Cities of China
Jiuyi HUANG ; Zhen HONG ; Wenzhi WANG
Chinese Journal of Prevention and Control of Chronic Diseases 2006;0(05):-
Objective To find out exposure level and distributional characteristics of risk factors for stroke in sampling population among communities. Methods Target population aged≥40 years were selected from Beijing,Shanghai,Fuzhou and Tangshan by cluster sampling and grouped by area,age and gender. They were investigated face to face with a questionnaire which included general information and common risk factors of stroke. Body height,weight and levels of blood pressures were measured. Exposure rate of risk factors and its distributional characteristics of area and population were described. Results 23 471 individuals were enlisted into data analysis. Exposure rate of hypertension,heart disease,diabetes,family history of stroke,obesity,cigarette smoking and alcohol drinking were 27.73%,14.14%,5.19%,15.95%,11.28%,28.7% and 16.6%,respectively. There were significant differences between areas for all factors (P
7.Effect of high glucose on the expression of KLF6 in human lens epithelial cell
Hong-tao, WANG ; Yong-zhen, BAO
Chinese Journal of Experimental Ophthalmology 2012;30(2):136-140
Background Epithelial-mesenchymaltransition (EMT)isamajorcontributortothe pathogenesis of posterior capsular opacification(PCO).Kruppel-like factor 6 (KLF6) is a zinc finger protein,which can be stimulated by high glucose in proximal tubule cells and involved in transforming growth factor beta (TGF-β)induced EMT of diabetic nephropathy.ObjectiveThis study was designed to investigate the effect of high glucose on the expression of KLF6 and its target genes( TGFB1,TGFBR1,COLIA1,HSP47) in human lens epithelial cells (LECs).MethodsHuman LECs(SRA01/04) were cultured and exposed to different concentration of glucose.The expressions of KLF6 mRNA and protein were analyzed by real time polymerase chain reaction( real time PCR) and western blot after treatment with high glucose.The expressions of KLF6 target genes were analyzed by real time PCR to evaluate the EMT of SRA01/04 cells.ResultsCompared with the control group(5.5 mmol/L),the relative mRNA levels of t-KLF6 and wt-KLF6 in SRA01/04 treated with high glucose(22.2,44.4,66.6 mmol/L) increased obviously (F =72.53,42.02,P<0.01 ).Then,the concentration of 22.2 mmol/L was used in the next experiments.The relative mRNA levels of t-KLF6 and wt-KLF6 increased to the peaks after treatment with high glucose for 12 h,and began to decrease after 24 h until lower levels after 48 h ( F =100.12,125.52,P < 0.01 ).Western blot showed that the expression of KLF6 protein was also upregulated by high glucose treatment.With the promotion of the expression of KLF6 gene,the relative mRNA levels of TGFB1,TGFBR1,COLlAl and HSP47 of treated cells also respectively increased after treatment for 12 h,and began to decrease after 24 h until nearly at the levels of the control groups after 48 h( F=6.73,162.35,64.39,12.05,P<0.05 ).ConclusionsIt was concluded that high glucose induced the expression of KLF6 in human LECs,and KLF6 transiently stimulated the expression of target genes TGFB1,TGFBRl,COLlAl and HSP47 which were mainly involved in the mechanism of EMT.
8.The thinking of improving the management level of scientific research via information management system
Dan WANG ; Hong ZHAI ; Zhen WANG ; Shujian GE
Chinese Journal of Medical Science Research Management 2015;28(3):275-277,282
This study is to explore that how to use the information management system to research composed of the management and sharing of research projects,study exchanging and technical guidance.The purpose is to improve the management efficiency and level of scientific research projects.Current study aimed to explore establish a digital management system
9.Effect of carteolol hydrochloride eye drops on 24-hour variation of intraocular pressure
Zhen WANG ; Xiaoyu LI ; Xiaoxiong WANG ; Hong DAI
Chinese Journal of Geriatrics 2011;30(5):393-395
Objective To investigate the effect of carteolol hydrochloride eye drops on 24-hour variation of intraocular pressure (IOP). Methods The 30 patients who had never used any anti-glaucoma eye drops were chosen, and their 24-hour variation of IOP (at 2:00 AM, 6:00 AM, 10:00 AM, 2:00 PM, 6:00 PM, 10:00 PM) were measured. Then carteolol hydrochloride eye drops were used twice a day (7:00 AM and 7:00 PM), 1-2 drops each time. Fifteen days later, their 24-h IOP was measured again and the data were analyzed. Results The average IOP at six monitoring points before treatment were (19.77±2.51) mm Hg, (19.52±2.34) mm Hg, (20.38±2.71) mm Hg, (20.07±3.65) mm Hg, (19.97±4.10) mm Hg and (19.97±4.31) mm Hg, the corresponding data after 15 days of treatment were (17.12±2.38) mm Hg, (17.42±2.60) mm Hg, (18.18±2.36) mm Hg, (18.02±3.77) mm Hg, (17.72±3.17) mm Hg and (17.35±3.40) mm Hg (t=11.68, P=0.000). The difference before and after treatment was (2.46±2.05) mm Hg during day and (2.17±1.88) mm Hg during night, and no significant difference was found between them. Conclusions Carteolol hydrochloride eye drops could significantly reduce the IOP, the decreased extent of 24-h IOP is stable.
10.Study on the Preventive and Therapeutic Effects of Xinmaitong Tablets on Model Rats with Atherosclerosis and Corresponding Mechanism
Jie CAO ; Qiaoli WANG ; Hong ZHAO ; Zhen WANG
China Pharmacy 2016;27(25):3499-3501
OBJECTIVE:To study the preventive and therapeutic effects of Xinmaitong tablets on model rats with atherosclero-sis (AS) and corresponding mechanism. METHODS:48 rats were randomized into normal group,model group,positive group (simvastatin tablets,2 mg/kg)and the groups of high,medium and low-dose(500,250,125 mg/kg)Xingmaitong tablets,with 8 rats in each group. The rats in all groups except for the normal group were fed high fat diets and given vitamin D3 ip for the estab-lishment of AS model. Meanwhile,the rats in the drug administration groups were given corresponding drugs ig,while those in the normal group and the model group were given normal saline ig,once a day,for 10 consecutive weeks. The levels of cholesterol (TC),triacylglycerol(TG),nitric oxide(NO)and endothelin 1(ET-1)in serum were determined. The pathological change of the aorta tissue was observed under the light microscope,and the size of the aortic atherosclerotic plaque and intima thickness were measured. RESULTS:Compared to the normal group,the rats in the model group had significantly higher levels of TC,TG and ET-1 in serum,a markedly larger aortic atherosclerotic plaque,remarkably thicker intima and much lower level of NO(P<0.01);and obvious aortic atherosclerotic plaque formation was found. Compared to the model group,the above-mentioned indexes of the rats in all drug groups all improved obviously (P<0.05 or P<0.01),except that the decrease in TC in serum of the rats in the group of low-dose Xinmaitong tablets was not significant,which were positively correlated with dose;and the aortic lesion in drug groups was found to be improved. CONCLUSIONS:Xinmaitong tablets have certain preventive and therapeutic effect on the model rats with AS by a mechanism which may be related to the reduction in lipid deposition and the size of an atherosclerotic plaque,the improvement in NO/ET balance and the alleviation of an endothelial injury.