1. Metabolic Disorder and Changes of Islet Morphology and Function in Thyl-aSYN Transgenic Mice
Ge GAO ; Yong-Quan LU ; Wei-Jin LIU ; Ru-Ning YANG ; Qi-Di ZHANG ; Hui YANG
Chinese Journal of Biochemistry and Molecular Biology 2021;37(2):222-228
Parkinson's disease (PD) is the second major neurodegenerative disease.The pathogenesis of PI) is still unclear.It is generally believed that neural damage, mitochondrial dysfunction, inflammation, oxidative stress and autophagy dysfunction caused by the transmission and aggregation of a- synuclein play an important role in the occurrence and development of PD.More and more research show- that metabolic disorder is one of the pathogenesis of PD.We examined whether overexpression of a- synuclein could induce metabolic disorder in mice and the possible mechanisms.Mice were divided into two groups: Thyl-aSYN transgenic mice (TG) and the control wild-type (WT) group.The rotarod test was used to analyze motor function in mice.We detected the body weight, plasma insulin content, glucose tolerance and insulin tolerance in the two group mice.The morphology of islets in the two groups were observed by hematoxylin eosin (HE) staining, and the islets were isolated to detect the glucose- stimulated insulin secretion (GSIS).The results showed that compared with the WT group, exercise tolerance of 12-month-old TG group decreased by 23.1% (P < 0.05) , body weight increased by 7% (P < 0.01), glucose tolerance decreased (P < 0.05), insulin tolerance decreased (P < 0.05), and insulin contents in the peripheral blood decreased by 20% (P < 0.05).Compared with the WT group, the levels of ce -syn proteins in the pancreas of the TG group increased by 1.32 times (P < 0.05) , the area of islets in the TG group decreased (P < 0.05 ) , the number of islets decreased (P < 0.01) , and the insulin secretion function decreased (P< 0.01).This study showed that the role of a-synuclein in PD is not limited to the damage of dopaminergic neurons, it also can affect metabolism and the morphology and function of peripheral organs, which provides a new theoretical basis for the pathogenesis of PD.
2.Association between plasma adiponectin and small, dense low density lipoprotein in patients with coronary artery disease
Gang CHEN ; Qin QIN ; Yang LI ; Bei REN ; Ya-Ru LU ; Lu KOU ; Ning YANG ; Jin-Ping FENG ; Bing-Rang ZHAO
Chinese Journal of Cardiology 2012;40(9):752-756
Objective To observe the association between adiponectin and small dense low-density lipoprotein (sLDL-c) in coronary artery disease (CAD) patients.Furthermore,we sought to determine the association between single nucleotide polymorphisms (SNP) rs1501299 ( + 276G/T ), rs266729 (-11365C/G) and the incidence of CAD.Methods Consecutive subjects with chest discomfort were examined by coronary angiography and divided into non-CAD [ n =250,147 male,mean age (60.26 ±7.52) years] and CAD [n =267,153 male,mean age (60.79 ±9.63) years] groups.Blood samples were collected from all participants following an overnight fasting for at least 12 hours.Plasma adiponectin levels were measured by competitive enzyme-linked immunosorbent assay (ELISA).The serum levels of sLDL-C and oxidized low-density lipoprotein (ox-LDL) were determined by ELISA.Genotypes in rs1501299 and rs266729 of the adiponeetin were determined by polymerase chain reaetion ( PCR ).Results 1.The adiponectin levels were significantly lower [ ( 306.17 ± 74.52 ) mg/L vs.( 321.78 ± 86.28 ) mg/L ],whereas sLDL-C and ox-LDL levels were significantly higher [ ( 276.30 ± 45.55 ) ng/L vs.( 249.00 ±32.02) ng/L and (545.06 ± 115.46 ) μg/L vs.(497.74 ± 106.09 ) μg/L,P < 0.05 ] in CAD group than non-CAD group.2.Adiponectin level was negatively associated with sLDL-C,whereas sLDL-C positively correlated with ox-LDL in all subjects.3.Genotype distribution and allele frequencies of rs1501299 and rs266729 were similar between CAD and non-CAD subjects and not related to the serum levels of adiponectin, sLDL-C and ox-LDL.Conclusions Reduced adiponectin and increased sLDL-C were independent risk factors for coronary artery disease.Genetic polymorphisms in rs1501299 and rs266729 were not linked with coronary artery disease.
3.Dietary patterns and its relationship with hypertension among rural residents in Hanzhong,Shaanxi province
Ru-Ru LIU ; Shao-Nong DANG ; Hong YAN ; Qiang LI ; Ya-Ling ZHAO ; Xiao-Ning LIU ; Rui-Hai YANG ; Yong REN
Chinese Journal of Epidemiology 2012;33(1):37-41
Objective To investigate the relationship between dietary patterns and hypertension in Hanzhong city of Shaanxi province.Methods A cross-sectional survey on dietarypattern and hypertension together with a semi-quantitative food frequency questionnaire was conducted among rural residents aged from 18 to 80 in Hanzhong of Shaanxi province in 2010.Factor analysis by SPSS was used to identify food patterns based on the frequency of food.Logistic regression was used to analyze the relationship between dietary patterns and hypertension.Results 2929 rural residents were investigated with an average age as 50.0 years old and average schooling-years as 6.8.The prevalence rate of hypertension was 34.3%,with 35.4% in males and 33.7% in females.Among 29 kinds of food under investigation,only 11 kinds with the frequencies of consumption more than 1 time per week.Four main factors were derived as four dietary patterns by factor analysis and they were diversity dietary pattern,alcohol dietary pattern,beverage dietary pattern and simple dietary pattern.Among them,the balanced dietary pattern was significantly associated with hypertension.All the participants were categorized into 4 groups (Q1-Q4) according to their factor scores,quartile with Q1 as a reference.The residents who were more closer to having balance dietary pattern,were under less risk of suffering from hypertension after controlling for age,sex,BMI,education and income.Compared to Q1,the Q4 had lower risk of hypertension (OR=0.59,95%CI:0.44-0.77) for the balanced pattern.Conclusion Dietary pattern could be related to the prevalence of hypertension.A rational diet with diversity of foods should be suggested as one of the major measures for the prevention of hypertension.
5.Characteristics of boningmycin induced cellular senescence of human tumor cells.
Xiu-Min ZHANG ; Ning GAO ; Ru-Xian CHEN ; Hong-Zhang XU ; Qi-Yang HE
Acta Pharmaceutica Sinica 2010;45(5):589-594
Cellular senescence is one of the important steps against tumor. This study was to observe the characteristics of boningmycin induced senescence of human tumor cells. MIT method and clone formation assay were used to detect the growth-inhibitory effect. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry. Protein expression was detected by Western blotting. The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells. Comparison to the similar action of doxorubicin, that boningmycin induced the features of cellular senescence in both cell lines, its due to the arrest at G2/M phase and an increase of ROS level. The molecular senescence marker P21 increased significantly after boningmycin treatment at a dosage of 0.1 micromol x L(-1), whereas a higher concentration of it induced apoptosis. The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.
Antibiotics, Antineoplastic
;
administration & dosage
;
pharmacology
;
Apoptosis
;
drug effects
;
Bleomycin
;
administration & dosage
;
analogs & derivatives
;
pharmacology
;
Carcinoma, Non-Small-Cell Lung
;
metabolism
;
pathology
;
Cell Cycle
;
drug effects
;
Cell Proliferation
;
drug effects
;
Cellular Senescence
;
drug effects
;
Cyclin-Dependent Kinase Inhibitor p21
;
metabolism
;
Dose-Response Relationship, Drug
;
Doxorubicin
;
pharmacology
;
Humans
;
KB Cells
;
Lung Neoplasms
;
metabolism
;
pathology
;
Poly(ADP-ribose) Polymerases
;
metabolism
;
Reactive Oxygen Species
;
metabolism
;
Tumor Suppressor Protein p53
;
metabolism
6.An epidemiological study on the norovirus detected in the field environment after an outbreak of norovirus gastroenteritis
Xiao-Hong ZHOU ; Hui LI ; Xing-Fen YANG ; Chang-Wen KE ; Hao-Jie ZHONG ; Li-Mei SUN ; Ru-Ning GUO
Chinese Journal of Epidemiology 2010;31(1):43-46
Objective To study the status of norovirus in environment of the patient's residence and water samples after a norovirus gastroenteritis outbreak, to provide evidences for the development of strategies for prevention and control of the disease. Methods After a norovirus gastroenteritis outbreak, anus swabs from the patient, swabs from the household environment and the water samples were collected to detect the norovirus by RT-PCR methods. Sequencing analysis was conducted on those positive specimens. Results Three specimens of the anus swabs from 9 patients and 2 samples of the 46 house environment swabs were positive to the virus. The latter were from the surface of water-closets of two families that the illness were asymptomatic. Among 5 water samples, only one was positive, which was the rivulet water that the feces of the villagers evacuated directly. Results showed that the sequences of the virus detected from the anus swabs of the patients, the swabs from the household environment and the samples of the rivulet water belonged to the same species. Conclusion It is necessary to strengthen activities as supervision and disinfection to the feces of the patients, especially on monitoring the feces that might have contaminated the water during the noroviru gastroenteritis outbreak.
7.Effect of lead acetate on the nerve growth factor protein expression and the regulation of thyroid hormone.
Rong ZHANG ; Yu-jie NIU ; Hui YANG ; Ben-hua WANG ; Yu-chun HOU ; Jian-ning CAI ; Dong-ru ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2003;21(6):408-412
OBJECTIVESTo study the effect of lead acetate on the expression of nerve growth factor (NGF) protein in rat brain and the regulation of thyroid hormone.
METHODSLead acetate was given to SD rats intraperitoneally ip. at the dosage of 25, 50 and 100 mg/kg respectively. 6-n-propyl-2-thiouracil (PTU) was used to make a hypothyroid model and then lead acetate was given at the dosage of 50 mg/kg body weight through i.p. The NGF protein expression in rat brain was observed by immunohistochemistry Triiodothyronine (T3), thyroxin (T4), TSH in serum and T3, T4 in brain tissue were determined by radio immunoassays (RIAs).
RESULTSThe average gray value of NGF protein in cerebral cortex of 50 mg, 100 mg treated groups (180.49 +/- 10.33, 169.72 +/- 19.75, respectively) were lower than the control (200.75 +/- 3.27, P<0.01). The area density of NGF protein in hippocampus of three treated groups (0.08 +/- 0.14, 0.12 +/- 0.02, 0.13 +/- 0.04, respectively) were significantly different from the control (0.025 +/- 0.015, P<0.05). The area density and the average gray value of NGF protein in lead acetate treated hypothyroid rat brain were of no significant changes. The levels of serum T3 in three treated groups [(0.68 +/- 0.02), (0.57 +/- 0.04), (0.54 +/- 0.02) microg/L respectively] and T4 [(28.30 +/- 1.83), (27.35 +/- 2.55), (24.00 +/- 3.01) microg/L] in serum were significantly lower while TSH [(6.34 +/- 1.13), (7.74 +/- 0.79), (9.16 +/- 0.77) IU] higher than those in the control [T3 (0.97 +/- 0.14) microg/L, T4 (54.50 +/- 3.70) microg/L and TSH (4.62 +/- 2.16) IU], and there was a good dose-response relationship. The levels of T3 in cerebral cortex of three treated groups [(13.26 +/- 0.81), (11.49 +/- 0.10), (10.42 +/- 1.19) pg/mg pro respectively] and T4 [(0.50 +/- 0.03), (0.49 +/- 0.13), (0.42 +/- 0.01) ng/mg pro] were significantly lower than those in control [(20.85 +/- 11.01) pg/mg pro, (0.76 +/- 0.14) ng/mg pro, P<0.05, P<0.01].
CONCLUSIONLead could increase the NGF protein expression in rat brain, which may be regulated by thyroid hormone.
Animals ; Brain Chemistry ; drug effects ; Immunohistochemistry ; Male ; Nerve Growth Factor ; analysis ; Organometallic Compounds ; toxicity ; Rats ; Rats, Sprague-Dawley ; Thyroid Hormones ; analysis ; blood ; physiology
8.The overview of the property system and characterization techniques of Chinese medicine materials before the pharmaceutical
Zhi-wei XIONG ; Ru-xi NING ; Ying-xia ZHAO ; Xiao-xin HU ; Bing YANG ; Yuan-pei LIAN ; Liang FENG ; Xiao-bin JIA
Acta Pharmaceutica Sinica 2021;56(8):2048-2058
At present, the modernization of Chinese medicine preparations (CMPs) is still a challenging task. The 3 typical Chinese medicine materials (CMMs) used for preparing CMPs are the powders, extracts, and components of Chinese medicine and their properties of CMMs are important for designing CMPs. Basing on our long term research, we have established a property system for CMMs according to the state of CMMs under an exactly condition and according to the interaction characteristics between substances. The property system could be divided into 5 categories: material composition, spatial structure, body property, surface property, physicochemical properties, and they could also be divided into 18 subcategories. Furthermore, we also established the corresponding index and characterization system, where the 61 indexes and characterization techniques were systematically summarized. At last, we hope that the article will promote the modernization of CMPs.
9.Dysbiosis of lung commensal bacteria in the process of lung epithelial-mesenchymal transition in mice with silicosis
China Occupational Medicine 2022;49(05):514-
Objective -
To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial
( ) Methods -
mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were
, , , ( )
randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin
( ) , ( ) ( ) ,
AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for
, ,
the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL
of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model.
:
The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were
- ; ;
given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L
;
mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed
,
treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis
, ,
mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were
-
used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle
( - ), - ( - ) ( )
actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of
- -
E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of
(Col1a2) Results
collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the
,
blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal
,
distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of
, ,
infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the
, ,
VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent
degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of
- , Col1a2
α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank
( P ), -CAD
control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control
(P ) - , Col1a2
group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+
( P ), -CAD
NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were
(P ), Conclusion
higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis
, -
was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary
fibrosis and dysbiosis of the lung flora affected pulmonary EMT.
10.Biologic characteristics of the side population of human small cell lung cancer cell line H446
Wang BO ; Yang HUAN ; Huang YU-ZHENG ; Yan RU-HONG ; Liu FEN-JU ; Zhang JUN-NING
Chinese Journal of Cancer 2010;29(3):272-278
Background and Objective:Recently,the theory of cancer stem cells(CSCs)has presented new targets and orientations for tumor therapy.The major difficulties in researching CSCs include their isolation and purification.The aim of this study is to identify and characterize the side population(SP)cells in small cell lung cancer(SCLC)cell line H446,which Iays the foundation for the isolation and purification of CSCs.Methods:Fluorescence-activated cell sorting(FACS)was used to sort SP and non-SP (NSP)cells from H446,Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres.Reverse transcriptionpolymerase chain reaction(RT-PCR)and real-time PCR were used to evaluate the expression levels of the mRNA of CD133,ABCG2,and nucleostemin in both subgroups.The capacity of proliferation and the differences in drug resistance of both subgroups and unso rted cells were tested by the MTT method.The differentiation ability of both subgroups was determined by FACS.Proliferation was determined by subcutaneous tumor formation in nude mice.Results:The percent of Hoechst 33342 negative cells was about(5.1±0.2)%in H446 by fluorescence microscopy.The percent of SP cells was(6.3±0.1)%by flow cytometry.SP cells had a stronger capability of fOrming into tumOr spheres than NSP cells.The mRNA expression Ievels of ABCG2,CD133,and nucleostemin in SP cells were 21.60±0.26,7.10±0.14,and 1.02±0.08 folds higher than that in NSP cells(P<0.01,P<0.01,and P>0.05,respectively).In vivo,SP cells showed better proliferative ability and tougher viability when treated with drugs.SP cells can differentiate into NSP cells,but NSP cells cannot differentiate into SP cells.SP cells had a greater ability to form tumors.Conclusions:The H446 cell line contained some SP cells with stem cell properties.CD133 and ABCG2 may be cancer stem celI markers of SCLC.