3.Role of mitochondrial quality control in exercise-induced health adaptation.
Hu DING ; Zi-Yi ZHANG ; Jing-Wen ZHANG ; Yong ZHANG
Chinese Journal of Applied Physiology 2013;29(6):543-553
Long-term endurance training or physical activity has been confirmed not only to improve physical performance, but to bring about an obvious beneficial effect on human health; however, the mechanism of this effect is not clear. The most studied health adaptations in skeletal muscle response to endurance exercise are increased muscle glycogen level and insulin sensitivity, fiber type transformation toward oxidative myofibers, and increased mitochondrial content/function. Mitochondria are dynamic organelles in eukaryotic cells critical in physical performance and disease occurrence. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes and confer positive impacts on skeletal muscle contractile and metabolic functions. This review focused on the regulation of these processes by endurance exercise and discussed its potential benefits in health and disease. We presented evidence suggesting that exercise training potentiates not only the biogenesis of mitochondria but also the removal of old and unhealthy mitochondria through mitochondrial quality control.
Adaptation, Physiological
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Exercise
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Humans
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Mitochondria
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physiology
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Muscle Contraction
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Muscle, Skeletal
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physiology
4.Epidemiological characteristics of non-occupational carbon monoxide poisoning: an analysis of 385 cases.
Yi-jing ZHAO ; Min-juan YANG ; Xin-dong HU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2013;31(4):287-288
Adolescent
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Adult
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Carbon Monoxide Poisoning
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epidemiology
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China
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epidemiology
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Female
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Humans
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Male
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Middle Aged
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Young Adult
5.Construction and Genetic Analysis of Murine Hepatitis Virus Strain A59 Nsp16 Temperature Sensitive Mutant and the Revertant Virus
Guohui CHANG ; Baojun LUO ; Pin LU ; Lei LIN ; Xiaoyan WU ; Jing LI ; Yi HU ; Qingyu ZHU
Virologica Sinica 2011;26(1):19-29
Coronaviruses (CoVs) are generally associated with respiratory and enteric infections and have long been recognized as important pathogens of livestock and companion animals. Mouse hepatitis virus (MHV) is a widely studied model system for Coronavirus replication and pathogenesis. In this study, we created a MHV-A59 temperature sensitive (ts) mutant Wu"-ts18(cd) using the recombinant vaccinia reverse genetics system. Virus replication assay in 17C1-1 cells showed the plaque phenotype and replication characterization of constructed Wu"-ts18(cd) were indistinguishable from the reported ts mutant Wu"-ts 18. Then we cultured the ts mutant Wu"-ts 18(cd) at non-permissive temperature 39.5℃, which "forced" the ts recombinant virus to use second-site mutation to revert from a ts to a non-ts phenotype. Sequence analysis showed most of the revertants had the same single amino acid mutation at Nsp16 position 43. The single amino acid mutation at Nsp16 position 76 or position 130 could also revert the ts mutant Wu"-ts 18 (cd) to non-ts phenotype, an additional independent mutation in Nsp13 position 115 played an important role on plaque size. The results provided us with genetic information on the functional determinants of Nsp16. This allowed us to build up a more reasonable model of CoVs replication-transcription complex.
6.Application of temperature sensitive yeast models with definite target in the screening of potential human Pin1 inhibitors.
Jing ZHANG ; Xiao-Min HAN ; Wen-Hui HU ; Zong-Ru GUO ; Xiao-Bo HE ; Shu-Yi SI
Acta Pharmaceutica Sinica 2014;49(6):854-860
This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
Animals
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Apoptosis
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drug effects
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Cell Proliferation
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drug effects
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Cyclin D1
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metabolism
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Drug Screening Assays, Antitumor
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methods
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G1 Phase
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High-Throughput Screening Assays
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methods
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Humans
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Mice
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NIMA-Interacting Peptidylprolyl Isomerase
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Neoplasms
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pathology
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Peptidylprolyl Isomerase
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antagonists & inhibitors
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Temperature
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Xenograft Model Antitumor Assays
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Yeasts
7.The effect of emodin on the contraction of isolated jejunum smooth muscle of rats.
Pan HU ; Jing YANG ; Liu GAO ; Xiao HAN ; Li-Li JIANG ; Hui-Jie MA ; Zan GUO ; Yi ZHANG
Chinese Journal of Applied Physiology 2014;30(1):93-96
OBJECTIVETo investigate the effect of emodin on the contraction of jejunum smooth muscle and its underlying mechanisms.
METHODSRats were randomly divided into 7 groups (n = 6): control group, emodin group (1, 5, 10, 20 micromol/L), propranolol (PRO) plus emodin group, glibenclamide (GLI) plus emodin group, NG-Nitro-L-arginine Methyl Ester (L-NAME) plus emodin group, calcium free control group and calcium free emodin group. The rats were sacrificed by cervical dislocation and the small intestine was isolated. The jejunum segment specimens were mounted on an Organ Bath System with a tension transducer. The effect of emodin on contraction of jejunum smooth muscle was measured by BL-420E+ biological signal processing system and the amplitude (AM), tension (TE) and frequency (FR) of contraction were determined.
RESULTS(1) Emodin inhibited the tension and amplitude of jejunum smooth muscle contraction in a dose-dependent manner (P < 0.05, P < 0.01) while the frequency was not obviously influenced. (2) PRO (P < 0.05) or GLI (P < 0.01) partly abolished the inhibitory effect of emodin on jejunum smooth muscle. (3) L-NAME had no obvious effect on the inhibitory effect of emodin. (4) Emodin attenuated the contraction of jejunum smooth muscle induced by calcium chloride application into calcium free K-H solution (P < 0.01).
CONCLUSIONEmodin obviously inhibits the amplitude and tension, while has no influence on the frequency of jejunum smooth muscle contraction in rats. Activation of beta adrenergic receptor, open of ATP sensitive potassium channels, and inhibition of the extracellular calcium influx through calcium channels of smooth muscle cell membrane might be involved in the process.
Animals ; Calcium Signaling ; Emodin ; pharmacology ; Glyburide ; pharmacology ; Jejunum ; drug effects ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; NG-Nitroarginine Methyl Ester ; pharmacology ; Propranolol ; pharmacology ; Rats
8.Effect of CKJ recipe containing serum on activation of rat primary hepatic stellate cells, TGF-beta1 and its receptors.
Liang CHEN ; Qin FENG ; Jing-hua PENG ; Lin LIU ; Chun-geng LIANG ; Ya-mei HAI ; Yi-yang HU
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(2):210-215
OBJECTIVETo observe the effect of CKJ Recipe (consisting of Cordyceps sinensis polysaccharide, amygdaloside, and gypenosides) containing serum on the activation of rat primary hepatic stellate cells (rHSCs) and to explore its pharmacological mechanism.
METHODSrHSCs were isolated form liver and cultured for four days. Then they were divided into the normal control group, the model group, and the CKJ group. rHSCs in the model group and the CKJ group were treated with 2.5 ng/mL transforming growth factor beta1 (TGF-beta1) in serum-free DMEM for 24 h. Serum free DMEM (containing no TGF-beta1) was taken as the control for the normal control group. rHSCs in the CKJ group were treated with 5% CKJ-containing serum for 24 h. rHSCs in the other two groups were treated with 5% blank serum for 24 h.The protein expression level of a smooth muscle actin (alpha-SMA) was determined using high throughput screening (HCS) and Western blot. mRNA expression levels of alpha-SMA, collagen I (Col-I), platelet-derived growth factor receptor beta (PDGF-betaR), TGF-beta1, transforming growth factor beta receptor 1 (TGF-betaR1), and transforming growth factor beta receptor 2 (TGF-beta R2) were detected using quantitative RT-PCR.
RESULTSCompared with the normal control group, the protein expression level of alpha-SMA, mRNA expression levels of alpha-SMA, Col-I, PDGF-betaR, TGF-beta1, TGF-betaR1, and TGF-betaR2 significantly increased in the model group (P<0.05, P<0.01). Compared with the model group, the protein expression level of alpha-SMA, mRNA expression levels of alpha-SMA, Col-I, PDGF-betaR, TGF-beta1, TGF-beta1, and TGF-beta R2 significantly decreased in the CKJ group (P<0.05, P<0.01).
CONCLUSIONCKJ containing serum could inhibit the protein expression level of o-SMA, which was probably related with inhibiting TGF-beta1 and its related receptors.
Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hepatic Stellate Cells ; metabolism ; Rats ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; metabolism
9.Regulatory Effect of Qushi Huayu Recipe on Gene Expression Profiles of Fatty Liver Rats.
Qin FENG ; Ya-jun TANG ; Xiao-fei LI ; Sheng-xi MENG ; Jing-hua PENG ; Yu ZHAO ; Yi-yang HU
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(2):203-209
OBJECTIVETo observe the intervention and mechanism of Qushi Huayu Recipe (QHR) on gene expression profiles in high lipid diet induced fatty liver rats.
METHODSFatty liver model was prepared in 20 male SD rats using single high fat diet (88% common forage +2% cholesterol +10% lard). Four weeks after modeling they were divided into the model group and the QHR group according to random digit table, 10 in each group. QHR (at 0. 93 g crude drug/100 g body weight) and distilled water was respectively to rats in the QHR group and the model group by gastrogavage while modeling, once per day. Meanwhile, 10 SD male rats were recruited in a normal group, administered with equal volume of distilled water by gastrogavage. At the end of week 8 all rats were sacrificed, and blood and livers were collected for subsequent analysis. Contents of liver triglyceride (TG) and free fatty acid (FFA) , activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using biochemical assay. Pathological changes of liver tissue were observed using H&E and oil red O stain. Liver gene expressions were detected by Affymetrix gene expression profiles. Differentially expressed genes were compared between the QHR group and the model group, functions of differentially expressed genes and signal pathways involved analyzed. Ten differentially expressed genes involved in glycolipid metabolism with fold change more than 2 were selected for verification by real-time PCR.
RESULTS(1) Compared with the normal group, contents of liver TG and FFA, and serum activities of ALT and AST obviously increased in the model group (P <0. 01). Compared with the model group, contents of liver TG and FFA, and activities of ALT and AST obviously decreased in the QHR group (P <0. 05, P <0. 01). QHR could reduce high fat induced fatty degeneration of liver cells , alleviate inflammation, and improve pathological changes of liver tissue. (2) Compared with the model group, there were 80 differentially expressed genes (with fold change > 2, P < 0.05) with clear functions and appointed gene names, including 44 up-regulated and 36 down-regulated genes. Eighty genes were involved in 27 signal pathways with statistical difference, including glycerolipid metabolism, adipocytokine signaling pathway, insulin signal pathway, drug metabolism signal pathway, etc (P < 0.05). (3) RT-PCR results of 10 glycolipids metabolism regulating genes such as Gk, Scd1, Gpat2, G6pc, Irs1, and so on showed that all RT-PCR genes were completely coincide with up-regulated or down-regulated tendency in results of gene chips. 80% genes had approximate fold change.
CONCLUSIONQHR could regulate gene expressions related to fat metabolism, carbohydrate metabolism, anti-lipid peroxidation, and drug metabolism in high fat diet induced fatty liver rats, and its comprehensive pharmacological actions could be manifested.
Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Carbohydrate Metabolism ; Diet, High-Fat ; Drugs, Chinese Herbal ; pharmacology ; Fatty Acids, Nonesterified ; metabolism ; Fatty Liver ; metabolism ; Lipid Metabolism ; Lipid Peroxidation ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transcriptome ; drug effects ; Triglycerides ; metabolism
10.Effect of triptergium wilfordii polyglycosidium on content of Th1 and Th2 in child recurrent nephrotic syndrome.
Guo-Hua HU ; Zhu-Wen YI ; Jing-He WANG ; Jing-Chan YAO
China Journal of Chinese Materia Medica 2008;33(4):441-443
OBJECTIVETo study the effect of triptergium wilfordii polyglycosidium on the content of Th1 and Th2 in the treatment child patients of rcurrent nephrotic syndrome.
METHODPatients were randomized into treatment group and health group. Sixty-one patients in treatment group were treated with triptergium wilfordii polyglycosidium 1 mg x kg(-1) x d(-1) orally tid for 12 weeks. However, patients in health group was not treated with any drugs. Twelve weeks constituted one course of treatment and the content of IL-12, IL-2, TNF-alpha, IL-13, IL-6, IL-4 in peripheral blood was measured before and behind therapy.
RESULTIn treatment group, the content of serum cytokines behind therapy was significantly lower than that before therapy, except for IL-12.
CONCLUSIONTriptergium wilfordii polyglycosidium could reduce the cytokine level (except for IL-12) of Th1 and Th2, which could lead a therapeutic effect of in the child patients of RNS.
Child ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glycosides ; pharmacology ; Humans ; Interleukin-12 ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; Th1 Cells ; drug effects ; metabolism ; Th2 Cells ; drug effects ; metabolism ; Tripterygium ; chemistry ; Tumor Necrosis Factor-alpha ; metabolism