1.Research progress of endoplasmic reticulum stress in diabetic cardiomyopathy
Chinese Pharmacological Bulletin 2017;33(9):1200-1203
Diabetic cardiomyopathy(DCM) is a disease independently related with coronary artery atherosclerotic heart disease, hypertensive heart disease, valvular heart disease, congenital heart disease and other heart diseases that are uniquely associated with diabetes mellitus, and the pathological manifestations of DCM are mainly myocardial hypertrophy, interstitial fibrosis, necrosis and apoptosis.Endoplasmic reticulum is the central location of many important cellular functions, and endoplasmic reticulum swelling and functional disorder in diabetic cardiomyocytes, high blood sugar can cause endoplasmic reticulum stress, suggesting that endoplasmic reticulum stress(ERS) may be involved in the pathogenesis of diabetic cardiomyopathy and development.Based on this, this paper summarizes the progress of ERS in diabetic cardiomyopathy from the pathogenesis of diabetic cardiomyopathy, unfolding protein reaction and the related role of ERS in DCM.
2.Role of NADPH oxidase in high fat-induced injury in MIN6 islet βcells
Jing LI ; Dan CHEN ; Yu ZHOU ; Cuiyu BAO
Chinese Pharmacological Bulletin 2016;32(9):1317-1320,1321
Aim To explore the role of nicotinamide adenine dinucleotide phosphate ( NADPH ) oxidase in high fat-induced injury in MIN6 isletβ cells. Methods MIN6 islet β cells were exposed to different concen-trations of palmitic acid ( 0. 1 , 0. 3 , 0. 5 , 0. 8 mmol · L-1 ) for 48 h and different time points of 0. 5 mmol· L-1 palmitic acid(24,48,72,96 h). Cell viability was measured by MTT, the protein expression of NADPH oxidase subunits such as p22 phox , p47 phox , p67 phox and gp91 phox and apoptosis related proteins such as Bcl-2 and Bax were determined by Western blot. Results MIN6 islet cells exposed to palmitic acid at 0. 5 mmol ·L-1 for 48 h showed a decrease in their viability and an increase in the expression of NADPH oxidase sub-units(p22phox、p47phox、p67phox and gp91phox) and Bax(P<0. 05 ) , while Bcl-2 expression was significantly re-duced. the pretreat with NADPH oxidase inhibitor di-phenyliodonium( DPI,10 μmol · L-1 ) significantly in-hibited high fat-induced Bcl-2 and Bax expression( P<0. 05 ) . Conclusion Activated NADPH oxidase might play an important role in the treatment of high fat-in-duced injury in MIN6 islet cells.
3.A 2-year follow-up study on cognitive function of patients with Parkinson's disease
Cuiyu YU ; Weiguo LIU ; Ling CHEN ; Wuruo FENG
Chinese Journal of Behavioral Medicine and Brain Science 2014;23(7):601-604
Objective To investigate the change and its related risk factors of cognitive function of patients with Parkinson's disease(PD).Methods The cognitive function of 70 idiopathic PD patients were assessed with Montreal cognitive assessment scale (MoCA),and other PD related neuropsychological test batteries were used to evaluate their movement symptoms and non-movement symptoms such as depression and anxiety.Patients' personal information were collected at the same time.They were reassessed after 2 years.Results As the disease progressed,the MoCA score of the PD patients significantly reduced from (24.79±4.07) points to (21.69±5.22) points (P<0.01).Seven subdomains of MoCA were attenuated,and 5 of them reached statistical significance.Motor subtype was a main predictor of the outcome of the cognitive impairment in PD.Scores of MoCA total score,naming,language,abstract and directional domains reduced more notably in patients with postural instability gait difficulty(PIGD) than those in the tremor dominant(TD) patients.Conclusion Cognitive function of PD patients decreases obviously after 2 years.The patients' cognitive impairment should be identified and intervened as soon as possible,especially the patients with PIGD.
4.Effects of norepinephrine preconditioning and ischemic preconditioning on apoptosis and Bcl-2, Bax expression in rat myocardial cells during myocardial ischemic reperfusion
Fangzhou CHENG ; Guohua TANG ; Gengshan LI ; Xiqiu YU ; Yuanzhong LI ; Xinhua HE ; Cuiyu BAO ; Yu ZHOU
Chinese Journal of Pathophysiology 2000;0(08):-
AIM: To study the effects of norepinephrine preconditioning(NE-P) and ischemic preconditioning (IP)on apoptosis and Bcl-2, Bax expression in rat myocardial cells in myocardial ischemic reperfusion (I/R). METHODS: The model of rat ischemic-reperfusion was used to conduct NE-preconditioning. Apoptotic myocytes were detected with TUNEL. Bcl-2, Bax expression were detected with immunohistochemistry. RESULTS: The rate of apoptosis cells in I/R group was higher, the rate of apoptosis cells in NE-P group and IP was lower significantly than that in I/R group( P0.05). CONCLUSION: NE-P reduced myocyte apoptosis by I/R in rats; The expression of Bcl-2 ,Bax genes played an important role in myocardial apoptosis.
5.The synergistic effect of FGF-21 and insulin on regulating glucose metabolism and its mechanism.
Dan YU ; Cuiyu SUN ; Guopeng SUN ; Guiping REN ; Xianlong YE ; Shenglong ZHU ; Wenfei WANG ; Pengfei XU ; Shujie LI ; Qiang WU ; Zeshan NIU ; Tian SUN ; Mingyao LIU ; Deshan LI
Acta Pharmaceutica Sinica 2014;49(7):977-84
Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.
6.Therapeutic efficacy of three bispecific antibodies on rheumatoid arthritis mice models.
Qingcui LI ; Xiaohui HAN ; Bing ZHOU ; Wenfei WANG ; Guiping REN ; Cuiyu SUN ; Qiang WU ; Yinhang YU ; Liming XU ; Qiuying WANG ; Jianying QI ; Yuquan WEI ; Hongwei CAO ; Junyan HAN ; Deshan LI
Acta Pharmaceutica Sinica 2014;49(3):322-8
In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.
7.Effect of problem-solving therapy on clinical efficacy, cognitive and social function in senile patients with first episode depression
Hong CHEN ; Ligang WANG ; Jiao CHEN ; Hui YU ; Cuiyu XIN ; Chunxia WANG ; Lingli KONG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(1):45-50
Objective:To investigate the effect of problem-solving therapy (PST) on clinical efficacy, cognitive and social function in senile patients with first episode depression.Methods:From March 2020 to August 2021, a total of 86 patients with first onset elderly depression treated in the geriatric department of Qingdao Mental Health Center were selected. According to the random number table method, totally 86 patients were randomly divided into a study group and a control group, with 43 cases in each group. The control group was treated with antidepressant drugs and basic psychiatric nursing intervention. The study group received PST treatment on the basis of the control group for 8 weeks. The Hamilton depression scale-17 items(HAMD-17), Montreal cognitive assessment scale (MoCA), and social dysfunction screening scale (SDSS) were used to assess the degree of depression, cognitive function and social function in both groups. SPSS 18.0 was used for statistical analysis. Independent sample t-test was used for comparison between groups, paired sample t-test was used for comparison before and after treatment. Results:After 8 weeks of intervention, HAMD-17 scores and SDSS scores in the two groups were both significantly decreased compared with before intervention, and the differences between pre intervention and post intervention had statistical significance( t=3.067, 22.543, both P<0.05), while MoCA scores were significantly increased, and the difference between pre intervention and post intervention had statistical significance ( t=9.623, P<0.05). Compared with the control group after 8 weeks of intervention, the HAMD-17 score ((14.44±1.97), (15.58±2.66), t=2.260, P=0.026) and SDSS score((9.44±2.24), (13.00±1.73), t=8.242, P<0.001) of the study group were lower, and the score of MoCA ((25.44±1.28), (23.84±1.56), t=5.223, P<0.001) was higher. Conclusion:In addition to conventional antidepressant therapy, PST not only reduces the severity of depression in elderly patients with first episode depression, but also significantly improves their cognitive and social function.
8.The characteristics and gender differences of non-motor symptoms in early diagnosed Parkinson’s disease.
Yajie WANG ; Weiguo LIU ; Cuiyu YU
Journal of Apoplexy and Nervous Diseases 2022;39(1):28-32
To explore the characteristics and gender differences of non-motor symptoms(NMS) in De Novo Parkinson’s diseases (PD). Methods 203 newly diagnosed PD patients (102 males,101 females) and 255 healthy controls (110 males,145 females) were selected. The clinical data were collected and evaluated by mini-mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Hamilton Depression Scale (HAMD),Hamilton Anxiety Scale (HAMA),Parkinson’s disease Sleep Scale (PDSS),Unified PD Rating Scale Part III (UPDRS-III) and Hoehn Yahr (H-Y) stage. Non-motor questionnaire screening scale (NMSQ) was used to assess their non-motor symptoms,and compared the characteristics of NMS in different genders. Multivariate linear regression was used to analyze the influencing factors of NMDQ score in PD patients. Results 98.5% of PD patients had at least one NMS,among which forgetfulness ( 67.5%),depression (49.8%) were the most common. The total score and nine domains of NMS in PD group were significantly higher than those in healthy controls (all P<0.05). The rates of interest decline,depression,anxiety and excessive sweating in female in PD group were significantly higher than those in male,while the rate of dysphagia was significantly lower (all P<0.05). The rates of hallucination and sweating increase in female in healthy controls were significantly higher than those inmale,the rate of memory decline was significantly lower (all P<0.05). The total scores of NMS in male and female patients with PD were affected by HAMD and PDSS (all P<0.05),while male patients were more likely to be affected by the disease duration (β= 0.181,P=0.032). Conclusion The incidence of non motor symptoms in newly diagnosed PD patients is significantly higher than that in healthy controls and different in gender.