1.Dihydromyricetin improves Parkinson's disease-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Qi LI ; Nian CHEN ; Jin-Ding LUO ; Hui-Lin WU ; Zi-Han WANG ; Meng-Wei LI ; Shui-Dong FENG ; Hong-Yan LING
Acta Physiologica Sinica 2023;75(1):59-68
The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Rats
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Animals
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Parkinson Disease
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Rats, Sprague-Dawley
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AMP-Activated Protein Kinases
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Diabetes Mellitus, Type 2
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Autophagy-Related Protein-1 Homolog
2. Dihydromyricin inhibited hepatic lipid deposition induced by high-fat diet in obese mice by activating SIRT1-AMPK pathway
Zi-Han WANG ; Jin-Ding LUO ; Hui-Jie LYU ; Jian-Qin HE ; Hong-Yan LING ; Ying-Ru TIAN ; Shui-Dong FENG
Chinese Pharmacological Bulletin 2021;37(1):107-113
Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg
3. DHM improves cognitive dysfunction in T2DM rats by inhibiting hippocampal endoplasmic reticulum stress
Meng-Wei LI ; Hui-Jie LYU ; Zi-Han WANG ; Jin-Ding LUO ; Jian-Qin HE ; Si-Si YANG ; Hong-Yon LING ; Hui-Jie LYU ; Xing-Xing DING ; Shui-Dong FENG
Chinese Pharmacological Bulletin 2022;38(1):91-97
Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.
4.p73 gene expression in apoptotic process of acute myeloid leukemia cell line U937 induced by methotrexate.
Guang-Fen XIAO ; Qing LU ; Xiang-Dong YANG
Journal of Experimental Hematology 2002;10(2):104-107
The purpose of this investigation was to study the variation of p73 gene expression in the apoptotic process of acute myeloid leukemia (AML) cell line U937 induced by methotrexate (MTX). Morphological changes of apoptotic cells were observed with microscopy and Wright's + Giemsa staining. DNA ladder and cell cycle were examined by agarose gel electrophoresis and flow cytometry respectively. Using semi-quantitive reverse transcription-polymerase chain reaction (RT-PCR), the expression of p73 mRNA was examined. Results showed that MTX could induce U937 cell apoptosis effectively. Condensed nuclei, fragmentation of chromosome and DNA ladder were seen after 6 hour following treatment of MTX 5 micro mol/L. Sub-G(1) peak and S + G(2)/M arrest were also determined by FCM, but the quantity of p73 expression was generally constant. In conclusion, U937 cell apoptosis induced by MTX did not change p73 mRNA level.
Acute Disease
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Antimetabolites, Antineoplastic
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pharmacology
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Apoptosis
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drug effects
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genetics
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Cell Cycle
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drug effects
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Cell Division
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drug effects
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DNA, Neoplasm
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drug effects
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genetics
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metabolism
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DNA-Binding Proteins
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genetics
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Flow Cytometry
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Gene Expression Regulation, Neoplastic
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drug effects
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Genes, Tumor Suppressor
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Humans
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Leukemia, Myeloid
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drug therapy
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genetics
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pathology
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Methotrexate
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pharmacology
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Nuclear Proteins
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genetics
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RNA, Messenger
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drug effects
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genetics
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metabolism
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Tumor Protein p73
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Tumor Suppressor Proteins
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U937 Cells
5.Effect of Autophagy Over Liver Diseases.
Dong-Qian YI ; Xue-Feng YANG ; Duan-Fang LIAO ; Qing WU ; Nian FU ; Yang HU ; Ting CAO
Chinese Medical Sciences Journal 2016;31(1):65-68
In recent years, increasingly evidences show that autophagy plays an important role in the pathogenesis and development of liver diseases, and the relationship between them has increasingly become a focus of concern. Autophagy refers to the process through which the impaired organelles, misfolded protein, and intruding microorganisms is degraded by lysosomes to maintain stability inside cells. This article states the effect of autophagy on liver diseases (hepatic fibrosis, fatty liver, viral hepatitis, and liver cancer), which aims to provide a new direction for the treatment of liver diseases.
6. Correlation between progesterone receptor G1978T polymorphism and endometrial cancer
Jing ZHOU ; Chen ZHOU ; Ke LIAO ; Ailin QIU ; Zifen GUO ; Weilei DONG ; Jing ZHOU
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):400-406
To explore the relationship between progesterone receptor (PGR) gene G1978T polymorphism and endometrial carcinoma. METHODS: After searching PubMed, EMBASE, Wan-fang and CNKI databases for literatures on PGR G1978T genotyping of endometrial cancer patients, the data were extracted and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using STATA15. The whole blood samples of endometrial carcinoma cases (EC group) and normal women (control group) were collected. Allelic-specific primers matching G1978T wild type G allele and mutant type T allele were designed with 3' terminal phosphorothioate modification, and the two-directional primer extension was performed using Exo + polymerase to genotype PGR gene G1978T polymorphism and Sanger sequencing was used to verify the genotype. RESULTS: PGR gene G1978T mutation was marginally associated with endometrial carcinoma risk (ORper allele =1.10, 95%CI=0.98-1.24, P= 0.072). At the same time, only 1 normal blood samples were found with PGR gene G1978T mutation, and the differences in genotypes and allele frequency between the case group and the control group were not statistically significantP>0.05. CONCLUSION: The G1978T polymorphism of the PGR gene maybe not be associated with the risk of endometrial carcinoma.
7.Predictive value of three preoperative nutritional assessment methods in postoperative complications of gastrointestinal cancers.
Dong HAN ; Jun HE ; Qiu-lin HUANG
Chinese Journal of Gastrointestinal Surgery 2013;16(11):1067-1072
OBJECTIVETo compare the value of three preoperative nutritional assessment methods, European nutrition risk screening 2002(NRS 2002), mini-nutrition assessment(MNA) and subjective global assessment(SGA), in predicting postoperative complications of gastrointestinal cancer patients.
METHODSA total of 235 patients with gastrointestinal cancers, including 31 esophageal cancers, 82 gastric cancers, and 122 colorectal cancers, in our hospital from January 2012 to June 2013 were prospectively enrolled. Preoperative nutritional status was evaluated with above 3 methods respectively. Postoperative complication rates were compared among different preoperative nutritional status.
RESULTSAccording to SGA score, the morbidity of severe-moderate, mild and no malnourished patients was 40.5%(17/42), 25.3%(22/87) and 14.2%(15/106) respectively(P<0.01). According to MNA score, the morbidity of patients with malnutrition, at risk of malnutrition and without malnutrition was 32.9%(23/70), 24.7%(18/73) and 14.1%(13/92) respectively(P<0.05). According to NRS 2002, the morbidity of patients at malnutrition risk and without malnutrition risk was 27.6%(27/98) and 19.7%(27/137) respectively(P>0.05). Multiple regression analysis revealed that both SGA and MNA scores were predictive factors for the development of postoperative complications(both P<0.01). The sensitivity of SGA score for predicting complications was higher compared to MNA score (90.7% vs. 79.6%), while the specificity was similar(49.7% vs. 50.8%).
CONCLUSIONSBoth SGA and MNA scores can effectively predict the development of postoperative complications in gastrointestinal cancer patients, and SGA score has better sensitivity. SGA score is recommended for decision-making regarding preoperative nutrition support.
Gastrointestinal Neoplasms ; surgery ; Humans ; Nutrition Assessment ; Nutritional Status ; Postoperative Complications ; Preoperative Care
8.Analysis of the clinical effects of the modified halo pelvic frame for the treatment of severe scoliosis with rigidity.
Xi-zheng SONG ; Guo-liang YI ; Wen-jun WANG ; Hong-ke LI ; Dong WANG ; Lin-zhang SONG
China Journal of Orthopaedics and Traumatology 2011;24(9):737-741
OBJECTIVETo evaluate the clinical curative effect of the modified Halo pelvic frame and surgery for the treatment of severe scoliosis with rigidity.
METHODSFrom January 2004 to May 2010,50 patients with severe scoliosis patients with rigidity were treated in our hospital. Twenty-three patients were male and 27 patients were female, with a mean age of 10.8 years old, ranging from 4 to 16 years. Twenty-four patients were congenital scoliosis and 26 patiens were idiopathic scoliosis. The mean body height were (152.1 +/- 11.1) cm and the average Cobb angle of scoliosis and kyphosis were (91.8 +/- 14.5) degrees and (69.5 +/- 14.0) degrees respectively. All the patients were treated with three-stages modified Halo pelvic traction, the second stage anterior release and the third stage posterior correction. The amount of correction was determined by measuring the change of body height, the Cobb angles and correction rate of scoliosis as well as kyphosis before and after the operation.
RESULTSThe mean body height were correct to (158.5 +/- 10.5) cm. The average Cobb angle of scoliosis were correct to (30.8 +/- 7.9) degrees. The average Cobb angle of kyphosis were correct to (31.6 +/- 10.1) degrees. After the first stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean of (30.4 +/- 6.6)% correction and (22.3 +/- 5.2)% respectively; after the second stage, the average Cobb angle of scoliosis and kyphosis were changed with the mean (26.7 -/+ 5.1)% correction and (21.2 -/+ 6.0)% respectively; the third stage, above data were (33.7 -/+ 7.2)% and (27.1 +/- 5.3)%. Correction rate of scoliosis and kyphosis were (66.5 +/- 7.2)% and (55.1 +/- 6.4)% respectively by the modified Halo pelvic frame traction and surgery. Body height, the Cobb angles and correction rate of scoliosis and kyphosis on radiographs were different in all stages (P<0.05).
CONCLUSIONOperative complications of severe scoliosis with rigidity can be reduced and better deformity correction and trunk balance achieved by the modified Halo pelvic frame traction and surgery.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Retrospective Studies ; Scoliosis ; surgery ; Treatment Outcome
9.Treatment of thoracolumbar fractures in minimal invasive with percutaneous transpedical interbody bonegrafting.
Xi-zheng SONG ; Wen-jun WANG ; Dong WANG ; Zhi-xun YIN ; Wen-kai HU ; Cheng WANG
China Journal of Orthopaedics and Traumatology 2009;22(10):791-792
Adult
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Aged
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Bone Transplantation
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Female
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Fractures, Bone
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surgery
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Humans
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Male
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Middle Aged
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Thoracic Vertebrae
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injuries
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surgery
10.Effects of rosiglitazone on aortic function in rats with insulin resistant-hypertension.
Hong-Yan LING ; Shui-Dong FENG ; Shou-Hong ZHOU ; Bing-Xiang WANG ; Xian-Qing LIU ; Bi HU
Acta Physiologica Sinica 2005;57(2):125-131
Rosiglitazone (ROSI), thiazolidione peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activator, reduces insulin resistance in patients with type 2 diabetes (T2DM). It also improves vascular reactivity in T2DM patients and some animal models by unclear mechanisms. In order to investigate the effect of ROSI on aortic systolic and diastolic function of insulin resistant-hypertensive rats (IRHR) and the underlying mechanism, male Sprague-Dawley (SD) rats were fed with high fructose (HF) for 8 weeks to induce IRHR model. To verify IRHR model, systolic blood pressure (SBP), fasting blood sugar (FBS), fasting serum insulin (FSI) were measured respectively in each group, and insulin sensitive index (ISI) was also calculated. Subsequently, the vascular function test was performed. The thoracic aortic ring of SD rats was mounted on a bath system. The effect of rosiglitazone on the contraction elicited by L-phenylephrine (PE) and potassium chloride (KCl) and the relaxation induced by acetylcholine (ACh) and sodium nitroprusside (SNP) were measured. To explore the mechanism, nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) was used and serum nitric oxide (NO) was measured. The results obtained were as follows: (1) Rosiglitazone reduced the level of SBP, serum insulin and improved insulin resistance in IRHRs. (2) The contractive responses of thoracic aortic rings to PE and KCl were enhanced and the relaxation response to ACh was depressed significantly in the HF group, and the effect was reversed by ROSI. (3) After pretreatment with L-NAME, the relaxation response to ACh was further impaired in the HF group, this effect was partly reversed by ROSI. (4) Sodium nitroprusside (SNP)-induced vasodilator responses did not differ significantly among the groups. (5) Aortic systolic and diastolic function of the control group was not affected markedly by ROSI. (6) Compared with the control group, serum nitric oxide was significantly reduced in the HF group, but after rosiglitazone treatment it was remarkably increased. These findings suggest that ROSI can improve aortic diastolic function of insulin resistant-hypertensive rats, the mechanism of this effect might be associated with an increase in nitric oxide mediated partly by NOS pathway, a decrease in the level of blood pressure, serum insulin and the improvement of insulin resistance.
Animals
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Aorta
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drug effects
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physiopathology
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Hypertension
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drug therapy
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physiopathology
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Insulin Resistance
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Male
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Nitric Oxide
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blood
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Thiazolidinediones
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pharmacology
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therapeutic use
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Vasodilation
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drug effects
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Vasodilator Agents
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pharmacology
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therapeutic use