2.The latest research progress of torpor occurrence mechanism
Zi-yu ZHU ; Jian-wei JIANG ; Jian-jun ZHANG
Acta Pharmaceutica Sinica 2021;56(6):1532-1536
Torpor refers to a state in which the metabolic activity in the body of the living animal is greatly reduced during the period of reduced food supply, which is manifested as a substantial decrease in body temperature, metabolic level, and exercise level. Mammals have a strict body temperature regulation system to maintain a constant body temperature. When the energy supply is insufficient for a long time, some mammals will enter a hibernation state. Torpor is very similar to the hibernation state. The research on the mechanism of torpor state is of great significance in aerospace, military medicine and other fields. This review summarizes the specific mechanisms regulating the occurrence of torpor from four aspects: adenylate cyclase activating polypeptide (adcyap) neurons, leptin, pyroglutamylated RFamide peptide (QRFP) neurons, and sympathetic nervous system, aiming to provide ideas for further research on the mechanism of torpor.
3.YZG-330 regulates the TRPM8 ion channel through the P38 MAPK signaling pathway to reduce body temperature in mice
Zi-yu ZHU ; Yuan-zhi YU ; Yue YUAN ; Jian-jun ZHANG
Acta Pharmaceutica Sinica 2022;57(5):1336-1343
Preliminary research in our laboratory found that compound YZG-330 can reduce mouse body temperature, which could be blocked by adenosine A1 receptor (A1R) antagonist DPCPX. Based on the downstream signaling pathway of the A1R, the mechanism by which YZG-330 lowers body temperature was further studied. The pharmacodynamics of YZG-330 was evaluated by measuring the rectal temperature; expression of the transient receptor potential (TRP) ion channel, the P38 protein and its phosphorylated form in mouse hypothalamic homogenate were detected by Western blotting. A Ca2+ fluorescent probe, Fluo-3AM, was added to cells to detect the effect of YZG-330 on the Ca2+ content of mouse hypothalamic cells. YZG-330 dose-dependently reduced the body temperature in mice, and the selective P38 inhibitor SB-203580 (20 mg·kg-1, i.p.) significantly inhibited the hypothermic effect of YZG-330. A TRPM8 antagonist 2 (0.1 μg per mouse, i.c.v.) markedly attenuated the hypothermic effect of YZG-330 (0.25 or 1 mg·kg-1, i.p.). YZG-330 (2 mg·kg-1, i.p.) significantly increased the phosphorylation of P38, an effect that could be attenuated by the A1R antagonist DPCPX (5 mg·kg-1, i.g.) in mouse hypothalamus. In addition, YZG-330 also prominently enhanced the expression of TRPM8, which could be blocked by SB-203580; YZG-330 (0.1-10 μmol·L-1) increased intracellular Ca2+ concetration in mouse hypothalamic cells in a dose-dependent manner, and was inhibited by the A1R inhibitor DPCPX (0.5 and 1 μmol·L-1) and TRPM8 antagonist 2 (1 μmol·L-1). In conclusion, YZG-330 exerts its hypothermic effect by activating the A1R to promote the phosphorylation of P38 protein and thereby up-regulating the expression and activity of the TRPM8 ion channel, resulting in increased intracellular Ca2+ concentration to stimulate mouse hypothalamus cells to down-regulate body temperature. All animal experiments were approved by the Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences.
4.Studies on drug resistance genes among 49 strains of extended-spectrum beta-lactamase-producing bacteria
Zi-Yong SUN ; Li-Ming CHEN ; Xu-Hui ZHU ; Li LI ; Bei ZHANG ; Yun-Song YU ;
Chinese Journal of Laboratory Medicine 2003;0(09):-
Objective To investigate the drug resistance genes of extended-spectrum beta- lactamase-producing bacteria in 49 strains.Methods Extended-spectrum ?-lactamase -producing strains were detected by the disc diffusion test.The techniques of polymerase chain reaction,sequence analysis, pulsed-field gel electrophoresis were used to analyze the genotype and homology of extended-spectrum ?- lactamase-producing strains.Results The incidence of ESBL-producing strains from E.coli,K pneumoniae,K oxytoca,was 20% in 2000,and 40% in 2003.Among the 49 ESBLs producers the most common genotype was CTX-M-14( n=33).The others were CTX-M-3,CTX-M-9,CTX-M-12,CTX-M-15, CTX-M-24 and SHVSa.Both two CTX-M subtypes,CTX-M-3 and CTX-M-14,were detected in one strain. However,4 ESBL-producing strains confirmed by phenotype remained untyped.The results showed that the ESBLs producers were not closely related,except for two strains of E.coli and two strains of K.pneumoniae which were homgenic respectively.Concolusions The incidence of ESBL-producing strains increases with years.The most common genotype of ESBLs is CTX-M.There is no evidence for epidemiologic spread of ESBL-producers by pulsed-field gel electrophoresis.
5.Analysis of X-ray signs of cervical spondylosis between vertebral artery type and radiculopathy.
Min-Shan FENG ; Jing-Hua GAO ; Li-Guo ZHU ; Zi-Long MA ; Chun-Yu GAO ; Hong-Lei DING
China Journal of Orthopaedics and Traumatology 2015;28(4):330-334
OBJECTIVETo improve the X-ray diagnosis of cervical spondylosis of vertebral artery type (VCS).
METHODSA blinded design research. The X-ray signs both 60 patients with VCS and 60 patients with cervical spondylotic radiculopathy were collected from January 2011 to November 2012. There were 36 males and 84 females, aged from 25 to 65 years old with an average of (48.4 ± 12.3) years old. Cervical curvature, atlanto-occipital joint angle, atlanto-axial joint angle, C2/C3 joint angle and lower cervical instability condition and segmental distribution were measured and recorded by X-rays. These data were analyzed and compared between the two groups after unblended. Combined with clinical manifestations,the X-ray imaging features of VCS were further analyzed.
RESULTSThere was significant difference in cervical curvature between two groups in anteflexion X-ray films (P < 0.05). There was significant difference in extension degree of atlanto-occipital joint angle between two groups (P < 0.01). There was significant difference in atlanto-axial joint angle between two groups in lateral X-ray films (P< 0.05). There was significant.difference in anteflexion degree of atlanto-axial joint angle between two groups (P < 0.05). There was no significant difference in C2/C3 joint angle between two groups. There was no significant difference in the lower cervical instability condition and segmental distribution between two groups. In VCS group, the mild and moderate dizziness was main symptom, flexion and extension activities of neck was most common cause in the dizziness; and always accompanied with headache; tenderness mostly concentrated in the upper cervical area.
CONCLUSIONBoth X-ray signs and clinical manifestations can prompt the abnormalities of the upper cervical structure or function in patients with VCS. Anteflexion activities of neck observed by functional position of X-ray films should be emphasized in diagnosis of VCS.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Radiculopathy ; diagnostic imaging ; Radiography ; Spondylosis ; diagnostic imaging ; Vertebral Artery ; X-Rays
6.Dynamic changes of IL-1β in rat myocardium during hypoxia/ reoxygenation transition.
Jin-bo HE ; Cai-ying BAO ; Yu-zhu YE ; Zi-yin LUO ; Lei YING ; Wan-tie WANG
Chinese Journal of Applied Physiology 2015;31(1):27-30
OBJECTIVETo investigate the expression profile of interleuki-1β (IL-1β) in rat myocardium at different time points during hypoxia/reoxygenation(H/R)transition.
METHODSThe isolated Langendorff perfused rat heart model was established.Forty SD rats were randomly divided into sham group (A group) and hypoxia/reoxygenation group (H/R group). The H/R group rats were subdivided into H/R 0.5 h group(B group), H/R 1 h group(C group), H/R 2 h group(D group)according to reoxygenation time. The left ventricular development pressure(LVDP), maximal rates of increase/decrease of the left ventricular pressure(±dp/dtmax) were continuously recorded. The concentration of interleukin-1β(IL-lβ) and creatine kinase-MB (CK-MB) in myocardium was measured by ELISA. The mRNA expression of IL-lβ in myocardium was determined by RT-PCR. Microstructure of myocardium was observed under light microscopy.
RESULTSThe value of LVDP and ±dp/dtmax in hypoxia/reoxygenation group rat were significantly lower than that in sham group(P < 0.05). The expression of IL-lβ and CK-MB at protein level and the expression of IL-1β at mRNA level in hypoxia /reoxygenation group were higher than that in sham group(P < 0. 05). There were significant differences of the above parameters among H/R 0.5 h, 1 h, 2 h group(P <0.05). The concentration of IL-1β and CK-MB, the mRNA expression of IL-1β were higher in H/R 2 h group than that of other groups(P < 0.05).
CONCLUSIONThe high expression of IL-Iβ in myocardium after myocardial hypoxia /reoxygenation in rats might lead to. ischemia/reperfusion injury.
Animals ; Creatine Kinase, MB Form ; metabolism ; Disease Models, Animal ; Hypoxia ; metabolism ; pathology ; Interleukin-1beta ; metabolism ; Myocardial Ischemia ; metabolism ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley
7.Screening for G1528C mutation in mitochondrial trifunctional protein gene in pregnant women with severe preeclampsia and new born infant
Rong WANG ; Zi YANG ; Jinming ZHU ; Jialue WANG ; Huixia YANG ; Qi WANG ; Guirong ZHAI ; Zhi LI ; Mei YU
Chinese Journal of Obstetrics and Gynecology 2000;0(10):-
Objective Severe preeclampsia, and hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) are serious complications of pregnancy, and evidence suggests a genetic basis for these conditions. A G1528C mutation in the alpha-subunit of the mitochondrial trifunctional protein (MTP) gene has been identified in association with these conditions. The aim of this study is to explore the carrier rate of the G1528C mutation in the MTP gene in pregnant women with severe preeclampsia, HELLP syndrome and in their newborns, as well as in a normal pregnant population, so as to determine its association with maternal liver disease among women in Beijing. Methods A multicenter, prospective, case control study was carried out. Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to screen the G1528C mutations in the MTP gene. One hundred and forty cord blood samples from cases with severe preeclampsia (n=130) and HELLP syndrome (n=10) were collected. Ninety maternal peripheral blood samples among them (84 from severe preeclampsia and 6 from HELLP syndrome) were also collected for screening the common disease-causing mutation in Caucasians. Five hundred and sixty cord blood samples and 90 maternal peripheral blood samples obtained from normal pregnant women served as controls. Results The G1528C mutations in the MTP gene were not found in samples from women with severe preeclampsia and their newborns, from women with HELLP syndrome and their new borns, as well as in samples from the normal pregnant women and their new borns. Conclusions The common disease-causing mutation of G1528C in MTP gene in Caucasians is probably not a common mutation in Chinese Han people in Beijing. Further study is needed to expand the sample size among HELLP syndrome and maternal liver diseases in Chinese population.
8.Mechanism of arsenic trioxide-induced apoptosis in hepatic blastoma cells HepG2.
Ding YU ; Zi-hui WANG ; Li-yuan ZHU
Chinese Journal of Oncology 2003;25(2):120-123
OBJECTIVETo investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML).
METHODSHepG2 cells were cultured in MEM medium and treated with different concentrations of As(2)O(3) for either 24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and western blot were performed to observe the expression of PML.
RESULTSTUNEL positive apoptotic cells and DNA ladder could be detected in As(2)O(3) treated groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei almost disappeared after the treatment of 5 micro mol/L As(2)O(3).
CONCLUSIONAs(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration-dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei. The decreased expression of PML is closely correlated with apoptosis. Nuclear matrix associated protein PML could be the target of As(2)O(3) therapy.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Hep G2 Cells ; Hepatoblastoma ; chemistry ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; chemistry ; drug therapy ; pathology ; Nuclear Proteins ; analysis ; Oxides ; pharmacology ; Promyelocytic Leukemia Protein ; Transcription Factors ; analysis ; Tumor Suppressor Proteins ; analysis
9.Relationship between programmed death-ligand 1 and clinicopathological characteristics in non-small cell lung cancer patients.
Yan-yan CHEN ; Liu-bo WANG ; Hui-li ZHU ; Xiang-yang LI ; Yan-ping ZHU ; Yu-lei YIN ; Fan-zhen LÜ ; Zi-li WANG ; Jie-ming QU
Chinese Medical Sciences Journal 2013;28(3):147-151
OBJECTIVETo evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics.
METHODSFrom 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using χ(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages.
RESULTSPositive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021).
CONCLUSIONPD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.
Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen ; secretion ; Carcinoma, Non-Small-Cell Lung ; pathology ; secretion ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms ; pathology ; secretion ; Lymphatic Metastasis ; Macrophages ; pathology ; secretion ; Male ; Middle Aged ; Retrospective Studies
10.Ultrasonic bone mineral density of calcaneus in 1 816 healthy subjects in Guangxi autonomous region.
Zi-Qiang ZHU ; Cheng-Li XU ; Wei LIU ; Shao-Mei HAN ; Shu-Yu ZU ; Guang-Jin ZHU
Acta Academiae Medicinae Sinicae 2006;28(4):570-573
OBJECTIVETo study the relationship between ultrasonic bone mineral density (BMD) of calcaneus and age, height, and body weight, and to establish the normal reference value for stiffness index (SI) of healthy subjects in Guangxi autonomous region and provide scientific foundation for the diagnosis and prevention of osteoporosis.
METHODSSI of calcaneus in 1 816 healthy adults aged 11-90 years (775 men, 1 041 women) were measured with quantitative ultrasound. According to their ages, all the men and women were divided into 13 groups by 5-year age group.
RESULTSSI reached peak values in 21-25 year group in men (range: 111.45 +/- 21.19) and in 16-20 year group in women (range: 101.26 +/- 17.51). Then the SI value began to decline with aging. The SI featured by a typical dual-peak curve in women and the decrease rate of SI was faster in women than in men over 61 years. Multivariate linear regression analysis showed significantly negative correlation between SI and age (P < 0.001), positive correlation between SI and body weight (P < 0.05 for men; P < 0.01 for women), and positive correlation between SI and height in women (P < 0.01).
CONCLUSIONSI correlates with age, height, and weight. The acquired SI value may provide a reference for the diagnosis of osteoporosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Density ; Calcaneus ; diagnostic imaging ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; diagnosis ; epidemiology ; Ultrasonography