Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WE...Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor(LDLR)-related proteins.As WEEV declined as a human pathogen in North America over the past century,isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors.To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence,we determined cryoelectron microscopy structures of WEEV bound to human PCDH10,avian PCDH10,and human very-low-density lipoprotein receptor(VLDLR).We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors.A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain.Because WEEV recently re-emerged in South America after decades of inactivity,our findings have important implications for outbreak preparedness.展开更多
Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate t...Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.展开更多
Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6...Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .展开更多
Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review...Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.展开更多
To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced...To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]- ET1 binding. Marker enzyme activities, protein yield, and dry- to- wet weight ratio of cardiac membranes were measured. Results. Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]- ET1 binding study showed that during early stage of sepsis, the Bmax of ET1 receptors was increased by 30％ in sarcolemma but decreased by 19％ in light vesicles, while during late stage of sepsis, the Bmax was decreased by 24％ in sarcolemma but increased by 38％ in light vesicles.The total binding of sarcolemma and light vesicles was increased by 25％ during early stage of sepsis but decreased by 17％ during late stage of sepsis. Conclusions. These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.展开更多
Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Meth...Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET- 1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET- 1 levels increased significantly on week 2 and week 4 of pressure overload. ET- 1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41％ (P< 0.01) and 65％ (P< 0.01) in sarcolemma in H- 2 week and H- 4 week groups, but was decreased by 24％ (P< 0.01) and 21％ (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33％ (P< 0.01) and 57％ (P< 0.01) in group H- 2 week and H- 4 week, respectively. Conclusion. ET- 1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.展开更多
Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGF...Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.展开更多
To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy （ICP） susceptibility. Methods： In 14 cases of mild ICP, 14 cases...To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy （ICP） susceptibility. Methods： In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases （control group） with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results： The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference （P〉0.05） The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference （P〉0.05）; the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group （P〈0.05）. The expression of ERβ in every group was higher than that of ERa （P〈0.05）. Conclusion： ERβ maybe play an important part in the etiology and development of ICP展开更多
A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % i...A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h-1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h ·mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h-1 in hypothyroid vs. 0.0356±0.0021 h-1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M- receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism.展开更多
The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and M...The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and Mab BuGR1(recognizing the DNA binding domain of GR_H).The specific binding peak of 0.98μmol/L[~3H]triamcinolone acetonide(TA)was higher than that of 52.50nmol/L[~3H]TA.The re-sult suggests that the antigenic determinants of GR_L are similar to those of GR_H.ThecDNA of rat liver GR_H was introduced into GR_H-and GR_L-negative mouse fibroblast cellline E82.A3 by calcium phosphate coprecipitation.A number of clones which expressGR_H were selected with G418(400μg/ml).The results of radioligand binding assay indicatethat GR_H gene is expressed successfully and GR_L also may be encoded by GR_H gene.展开更多
By means of radioligand binding assay, both receptors of the malondialdehyde modified low density lipoprotein (MDA-LDL) and the oxidatively modified LDL(o-LDL) on the mouse's peritoneal macrophage (MPM) were studi...By means of radioligand binding assay, both receptors of the malondialdehyde modified low density lipoprotein (MDA-LDL) and the oxidatively modified LDL(o-LDL) on the mouse's peritoneal macrophage (MPM) were studied. The results show that there were high affinity receptors for MDA-LDL and o-LDL on the MPM and both receptors had multiplicity of configuration based on the competitive-inhibition curve or parameters IC50 and Ki, and the acetylated LDL (Ac-LDL) and dextran sulfate can both competitively inhibit MDA-LDL or oLDL binding to these receptors in some degree.It is meanful to study the scavenger receptor multiplicity and its relationship to the genesis, protection and treamtent of atherosclerosis.展开更多
Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats we...Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)展开更多
Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: T...Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: The cathartic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207.00±22.90 fmol/mg·p vs 82.00±14.23 fmol/mg·p, P < 0.01;3.30±0.45 mmol/L vs 2.40±0.57 mmol/L,P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957.00±102.41 fmol/mg·p vs 459.00±52.41 fmol/mg·p, P<0.01), but no significant difference of affinity was found between the two groups. Conclusion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.展开更多
Objective： To explore the role of activated liver X receptor α （LXRα） on the expressions of interleukin-1 receptor associated kinase-4 （IRAK-4） and NF-kappaB （NF-κB） in the inflammatory response which induce...Objective： To explore the role of activated liver X receptor α （LXRα） on the expressions of interleukin-1 receptor associated kinase-4 （IRAK-4） and NF-kappaB （NF-κB） in the inflammatory response which induced by LPS in the Kupffer cells and to investigate the possible mechanisms of LXRα negative regulation of inflammatory response. Methods： The Kupffer cells were isolated from male Kunming mice by collagen perfusion in situ. And these cells were divided into 4 groups： normal control group, LPS treatment group, LXRct agonist T0901317 treatment group, LPS and T0901317 combined treatment group. The LPS treatment group were treated with a final concentration of 1 μg/ml LPS in RPMI 1640 and cultured for 6 h, the T0901317 treatment group were treated with a final concentration of 5 μg/ml in RPMI 1640 and cultured for 24 h, and the combined treatment group received pre-culture for 24 h with a final concentration of 1μg/ml T0901317 in RPMI 1640 and then cultured for 6 h with a final concentration of 5 μg/ml LPS in RPMI 1640. All groups were cultured for 30 h. The expression of LXRα, IRAK-4 and NF-κB at mRNA and protein levels were detected by real-time PCR and Western blotting, and the TNF-α and IL-1β levels were detected by ELISA. Results： The levels of LXRα mRNA and protein were highest in T0901317 group, and lowest in LPS group （P〈0.05）. The level of IRAK4 and NF-κB mRNAs and proteins were evidently lower in the Combined-treated group than in LPS group （P〈0.05）. And the level of TNF-α and IL-1 were observed highest in LPS group （P〈0.05）, but no difference among the Control group, T0901317 group and Combined-treated group （P〉0.05）. Conclusion： These date suggest that the LXR agonists can effectively up-regulate the expressions of LXRα mRNA and protein and inhibit the inflammatory response. This may be via down-regulating the expressions of IRAK4 and NF-κB at mRNA and protein levels.展开更多
Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneou...Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.展开更多
The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunoh...The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunohistochemistry(ABC),Western blot and North-ern blot technique,It was found that the expression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-Ⅰ-R was signif-icantly higher in PHC than in normal liver tissue and the expression of IGF-Ⅱ and IGF-Ⅱ-R wasremarkably higher in the juxtacancerous liver tissue from PHC patients than in PHC proper.Itwas noteworthy that the expression of IGF-Ⅱ in both the cancer proper and the juxtacancerousliver tissue was characterized by its fetal type.Besides,the expression of CSF-Ⅰ-R was signifi-cantly higher in PHC than in the juxtacancerous liver tissue.It is believed that the abnormal ex-pression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-I-R in PHC and the juxtacaneerous liver tissue might berelated to the autocrine mechanism of human PHC.展开更多
BACKGROUND: Retinoid X receptor(RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H2O2-induced apoptosis of H9c2 ventricular cells...BACKGROUND: Retinoid X receptor(RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H2O2-induced apoptosis of H9c2 ventricular cells in rats. But the protective effect and mechanism of activating RXR in cardiomyocytes against hypoxia/reoxygenation(H/R)-induced oxidative iniury are still unclear.METHODS: The model of H/R injury was established through hypoxia for 2 hours and reoxygenation for 4 hours in H9c2 cardiomyocytes of rats. 9-cis-retinoic acid(9-cis RA) was obtained as an RXR agonist, and HX531 as an RXR antagonist. Cultured cardiomyocytes were randomly divided into four groups: sham group, H/R group, H/R+9-cis RA-pretreated group(100 nmol/L 9-cis RA), and H/R+9-cis RA+HX531-pretreated group(2.5 μmol/L HX531). The cell viability was measured by MTT, apoptosis rate of cardiomyocytes by flow cytometry analysis, and mitochondrial membrane potential(ΔΨm) by JC-1 fluorescent probe, and protein expressions of Bcl-2, Bax and cleaved caspase-9 with Western blotting. All measurement data were expressed as mean±standard deviation, and analyzed using one-way ANOVA and the Dunnett test. Differences were considered signif icant when P was <0.05.RESULTS: Pretreatment with RXR agonist enhanced cell viability, reduced apoptosis ratio, and stabled ΔΨm. Dot blotting experiments showed that under H/R stress conditions, Bcl-2 protein level decreased, while Bax and cleaved caspase-9 were increased. 9-cis RA administration before H/R stress prevented these effects, but the protective effects of activating RXR on cardiomyocytes against H/R induced oxidative injury were abolished when pretreated with RXR pan-antagonist HX531.CONCLUSION: The activation of RXR has protective effects against H/R injury in H9c2 cardiomyocytes of rats through attenuating signaling pathway of mitochondria apoptosis.展开更多
Estrogen and progesterone receptor (ER and PR) contents of 40 breastcancer patients were determined with immunofluorescent staining.Thedifferentiation of cancer cells was evaluated on the basis of histological andultr...Estrogen and progesterone receptor (ER and PR) contents of 40 breastcancer patients were determined with immunofluorescent staining.Thedifferentiation of cancer cells was evaluated on the basis of histological andultrastructural changes.It was found that there was a positive correlation of ERand PR contents with the cellular differentiation of breast cancer,and the lattercould be used to estimate the status of hormone receptors.Breast cancer is a malignant disease with heteropathological characteristics.In handling a breast cancerpatient,both the status of hormone receptors and the cellular differentiationshould be considered and the treatment varied with each pa(?)ent.For those witha well-differentiated cancer and rich hormone receptors,endocrine therapy shouldmainly be administered,while for those with a poorly-differentiated cancer and afew hormone receptors,chemotherapy would be of choice.展开更多
文摘Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor(LDLR)-related proteins.As WEEV declined as a human pathogen in North America over the past century,isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors.To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence,we determined cryoelectron microscopy structures of WEEV bound to human PCDH10,avian PCDH10,and human very-low-density lipoprotein receptor(VLDLR).We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors.A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain.Because WEEV recently re-emerged in South America after decades of inactivity,our findings have important implications for outbreak preparedness.
基金supported in part by the National Key Research and Development Program of China(2022YFD2100104)the Science and Technology Program of Shaanxi Province,China(2022JM-111)Graduate Innovation Fund of Dalian Polytechnic University。
文摘Punicalagin has been demonstrated to exhibit anti-oxidant and anti-inflammatory properties,but whether and how it could impact hypercholesterolemia remains not fully explored.The aim of this study was to investigate the influence of punicalagin on hypercholesterolemia in mice and its related mechanisms.After 6 weeks'intervention,punicalagin significantly reduced serum total cholesterol and low-density lipoprotein cholesterol(LDL-C)levels in mice fed a high-fat high-cholesterol(HFHC)diet.Meanwhile,punicalagin supplementation lowered hepatic cholesterol level,which corresponded to the down-regulation of cholesterol synthesis genes(Fdps,Cyp51)and up-regulated bile acid synthesis genes(Cyp7a1,Cyp27a1).In addition,bile acid reabsorption was retarded in punicalagin-fed mice through down-regulating ileal apical sodium-dependent BA transporter(ASBT).Furthermore,intestinal farnesoid X receptor(FXR)-fibroblast growth factor 15(Fgf15)pathway was inhibited while hepatic FXR-small heterodimeric partner(SHP)pathway was activated in punicalagin group.Microbiota analysis and targeted metabolomics showed that punicalagin decreased the abundance of bile-salt hydrolase(BSH)-producing bacteria(Clostridiaceae and Bifidobacteriaceae)and the ratio of primary BAs to secondary BAs.In conclusion,the cholesterol-lowering effect of punicalagin partly through down-regulating cholesterol synthesis and increasing cholesterol catabolism,which could be achieved by regulating gut microbiota,altering bile acid composition and modulating FXR signaling pathway.These findings indicate the potential application of punicalagin-related products as an alternative strategy for hypercholesterolemia prevention and mitigation.
文摘Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty- four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit＋ bosentan group and Nit＋ losartan group. Nitroglycerin tolerance was induced by 2- day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg－ 1· d－ 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg－ 1· d－ 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit＋ losartan group and Nit＋ bosentan group compared with Nit group [(31.95± 4.45 )％ vs (21.00± 3.69 )％ , P< 0.01 and (33.18± 6.16 )％ vs (21.00± 3.69 )％ , P< 0.01 ,respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50％ of the maximal response to SNP) was found in tolerant group[(34± 10) nmol/ L,P < 0.01 .The ET- 1 amounts in plasma and vascular tissue were markedly increased by 54％ and 60％ in Nit group compared with those in control group(P< 0.01).The ET- 1 amounts in plasma and vascular tissue were decreased by 30％ and 37％ in Nit＋ losartan group compared with those in Nit group (P< 0.01). Conclusion. Endothelin receptor antagonist and angiotensinⅡ receptor antagonist could prevent against the Nit tolerance .
基金the financial support provided by“Pioneer”and“Leading Goose”R&D Program of Zhejiang(2022C020122022C02078)。
文摘Bitterness,one of the 5“basic tastes”,is usually undesired by humans.However,abundant literature reported that bitter fruits and vegetables have beneficial health effects due to their bitter contributors.This review provided an updated overview of the main bitter contributors of typical bitter fruits and vegetables and their health benefits.The main bitter contributors,including phenolics,terpenoids,alkaloids,amino acids,nucleosides and purines,were summarized.The bioactivities and wide range of beneficial effects of them on anti-cancers,anti-inflammations,anti-microbes,neuroprotection,inhibiting chronic and acute injury in organs,as well as regulating behavior performance and metabolism were reported.Furthermore,not only did the bitter taste receptors(taste receptor type 2 family,T2Rs)show taste effects,but extra-oral T2Rs could also be activated by binding with bitter components,regulating physiological activities via modulating hormone secretion,immunity,metabolism,and cell proliferation.This review provided a new perspective on exploring and explaining the nutrition of bitter foods,revealing the relationship between the functions of bitter contributors from food and T2Rs.Future trends may focus on revealing the possibility of T2Rs being targets for the treatment of diseases,exploring the mechanism of T2Rs mediating the bioactivities,and making bitter foods more acceptable without getting rid of bitter contributors.
基金This study was supported by the National Nature Scientific Fund (No.39730220).
文摘To study the redistribution of endothelin- 1 (ET- 1) receptors in two subcellular organelles , the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis. Methods. Sepsis was induced by cecal ligation and puncture (CLP). ET1 receptor was assayed by using [125I]- ET1 binding. Marker enzyme activities, protein yield, and dry- to- wet weight ratio of cardiac membranes were measured. Results. Septic rat heart exhibited two distinct phases: an initial hyperdynamic phase( 9h after CLP; early stage of sepsis) followed by a hypodynamic (18h after CLP, late stage of sepsis) phase. [125I]- ET1 binding study showed that during early stage of sepsis, the Bmax of ET1 receptors was increased by 30％ in sarcolemma but decreased by 19％ in light vesicles, while during late stage of sepsis, the Bmax was decreased by 24％ in sarcolemma but increased by 38％ in light vesicles.The total binding of sarcolemma and light vesicles was increased by 25％ during early stage of sepsis but decreased by 17％ during late stage of sepsis. Conclusions. These data indicated that ET1 receptors in the rat heart were externalized from light vesicles to sarcolemmal membranes during early hyperdynamic phase while internalized from surface membranes to intracellular compartment during late hypodynamic phase of sepsis.
基金the National Major Basic Research Program(No.G2000056905)
文摘Objective. In a model of rat cardiac hypertrophy, the changes in the distribution of ET- 1 receptors in two subcellular fractions, the sarcolemma and the light vesicles during myocardial hypertrophy were studied. Methods. Cardiac hypertrophy was produced by placing a constricting clip around the suprarenal abdominal aorta of rats, and ET- 1 receptor was assayed with radioactive analysis method. Results. It was found that plasma and ventricular ET- 1 levels increased significantly on week 2 and week 4 of pressure overload. ET- 1 binding studies showed that during myocardial hypertrophy, the maximum binding capacity (Bmax) was increased by 41％ (P< 0.01) and 65％ (P< 0.01) in sarcolemma in H- 2 week and H- 4 week groups, but was decreased by 24％ (P< 0.01) and 21％ (P< 0.01) in light vesicles. The sum of Bmax of sarcolemmal and light vesicle fractions was increased by 33％ (P< 0.01) and 57％ (P< 0.01) in group H- 2 week and H- 4 week, respectively. Conclusion. ET- 1 receptors in rat heart were externalized from light vesicles to sarcolemma, which may contribute to the development of myocardial hypertrophy.
基金Supported by National Natural Science Fund of China(31370920)Public Technology Research Program of Zhejiang Province(2014C33157)Medical and Health Research Project of Zhejiang Province(2014KYA225)
文摘Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.
文摘To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy （ICP） susceptibility. Methods： In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases （control group） with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results： The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference （P〉0.05） The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference （P〉0.05）; the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group （P〈0.05）. The expression of ERβ in every group was higher than that of ERa （P〈0.05）. Conclusion： ERβ maybe play an important part in the etiology and development of ICP
文摘A technique for studying in vivo the production rate and turnover rate constant of mouse brain M-receptors was established. A single injection of 25 mg / kg of Benzilylcholine Mustard to living mice resulted in 90 % irreversible block of brain M-receptors. The time course of the receptor density was then monitored by 3H-QNB binding assay and the production rate and turnover rate constant were calculated from the time course curve with a computer program. It was found that in normal mice the turnover rate constant was about 0.035 h-1 (half-life was about 20 h) and the production rate was 30-42 fmol / (h ·mg protein). Parallel experiments revealed a significant slow down of the turnover of brain M-receptors in hypothyroid mice (turnover rate constant was 0.0257±0.0012 h-1 in hypothyroid vs. 0.0356±0.0021 h-1 in normal) while the production rate was not changed significantly. The results suggest that thyroid hormones have a regulatory action on the turnover of brain M-receptors and the elevation of brain M-receptor density together with slow down of the turnover of brain M- receptors is probably one of the important mechanisms relevant to the brain dysfunction in hypothyroidism.
文摘The homogeneity between the high-and low-affinity glucocorticoid receptors(GR_H and GR_L)was testified by immunoaffinity chromatography using Mab N250(recognizing the immunogenic domain at the N terminal of GR_H)and Mab BuGR1(recognizing the DNA binding domain of GR_H).The specific binding peak of 0.98μmol/L[~3H]triamcinolone acetonide(TA)was higher than that of 52.50nmol/L[~3H]TA.The re-sult suggests that the antigenic determinants of GR_L are similar to those of GR_H.ThecDNA of rat liver GR_H was introduced into GR_H-and GR_L-negative mouse fibroblast cellline E82.A3 by calcium phosphate coprecipitation.A number of clones which expressGR_H were selected with G418(400μg/ml).The results of radioligand binding assay indicatethat GR_H gene is expressed successfully and GR_L also may be encoded by GR_H gene.
文摘By means of radioligand binding assay, both receptors of the malondialdehyde modified low density lipoprotein (MDA-LDL) and the oxidatively modified LDL(o-LDL) on the mouse's peritoneal macrophage (MPM) were studied. The results show that there were high affinity receptors for MDA-LDL and o-LDL on the MPM and both receptors had multiplicity of configuration based on the competitive-inhibition curve or parameters IC50 and Ki, and the acetylated LDL (Ac-LDL) and dextran sulfate can both competitively inhibit MDA-LDL or oLDL binding to these receptors in some degree.It is meanful to study the scavenger receptor multiplicity and its relationship to the genesis, protection and treamtent of atherosclerosis.
文摘Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial calcification.Methods Nicotine and vitamin D_3 treated rats were studied.Vascular calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)activity.The plasma and vascular Ang Ⅱ and endothelin levels were measured by using radioimmunoassay.Angiotensinngen and endothehn mRNA levels were determined by RT- PCR.Results The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P<0.01).Administration of the angiotensin receptor antagonist losartan,the endothelin receptor antagonist bosentan,and the angiotensin-converting enzyme inhibitor captopril reduced significantly the arterial calcium content,^(45)Ca^(2+)uptake and ALP activity.In addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P<0.05). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)
文摘Objective: To observe the changes of mu and kappa opioid receptors in the cathartic colon of rat, and to clarify that whether opioid receptors accounts for the occurrence of slow transit constipation (STC). Methods: The cathartic colon model of rat was made by feeding with laxatives. The activity of mu and kappa opioid receptors in the cathartic colon of rat was measured by radio-ligand binding assay. Results: Compared with the control group, the maximal binding capacity (Bmax) and affinity(Kd) of mu opioid receptor in cathartic colon group were significantly increased (207.00±22.90 fmol/mg·p vs 82.00±14.23 fmol/mg·p, P < 0.01;3.30±0.45 mmol/L vs 2.40±0.57 mmol/L,P < 0.05). The maximal binding capacity of kappa opioid receptor also showed a great increase (957.00±102.41 fmol/mg·p vs 459.00±52.41 fmol/mg·p, P<0.01), but no significant difference of affinity was found between the two groups. Conclusion: The mu and kappa opioid receptors may be involved in the functional disorders of cathartic colon.
基金the National Natural Science Foundation of China (30530360 and 30772098)
文摘Objective： To explore the role of activated liver X receptor α （LXRα） on the expressions of interleukin-1 receptor associated kinase-4 （IRAK-4） and NF-kappaB （NF-κB） in the inflammatory response which induced by LPS in the Kupffer cells and to investigate the possible mechanisms of LXRα negative regulation of inflammatory response. Methods： The Kupffer cells were isolated from male Kunming mice by collagen perfusion in situ. And these cells were divided into 4 groups： normal control group, LPS treatment group, LXRct agonist T0901317 treatment group, LPS and T0901317 combined treatment group. The LPS treatment group were treated with a final concentration of 1 μg/ml LPS in RPMI 1640 and cultured for 6 h, the T0901317 treatment group were treated with a final concentration of 5 μg/ml in RPMI 1640 and cultured for 24 h, and the combined treatment group received pre-culture for 24 h with a final concentration of 1μg/ml T0901317 in RPMI 1640 and then cultured for 6 h with a final concentration of 5 μg/ml LPS in RPMI 1640. All groups were cultured for 30 h. The expression of LXRα, IRAK-4 and NF-κB at mRNA and protein levels were detected by real-time PCR and Western blotting, and the TNF-α and IL-1β levels were detected by ELISA. Results： The levels of LXRα mRNA and protein were highest in T0901317 group, and lowest in LPS group （P〈0.05）. The level of IRAK4 and NF-κB mRNAs and proteins were evidently lower in the Combined-treated group than in LPS group （P〈0.05）. And the level of TNF-α and IL-1 were observed highest in LPS group （P〈0.05）, but no difference among the Control group, T0901317 group and Combined-treated group （P〉0.05）. Conclusion： These date suggest that the LXR agonists can effectively up-regulate the expressions of LXRα mRNA and protein and inhibit the inflammatory response. This may be via down-regulating the expressions of IRAK4 and NF-κB at mRNA and protein levels.
文摘Objective: To investigate membrane tumor necrosis factor receptor 1 protein expression level in decidua and concentration of soluble tumor necrosis factor receptor 1 in serum in women with unexplained early spontaneous abortion, threatened abortion, and compare the levels with healthy pregnant women. Methods: Thirty-seven women with unexplained early spontaneous abortion, 27 women with threatened abortion, and 34 healthy pregnant women undergoing artificial abortion of pregnancy at 6 - 10 weeks of gestation were selected. Decidual samples were collected when women were undergoing artificial abortion, and blood samples were collected at the same time. The level of membrane tumor necrosis factor receptor 1 in decidua was detected by flow cytometer, and the concentration of soluble tumor necrosis factor receptor 1 in sera was measured with an enzyme-linked immunosorbent assay. Results: The percentages of membrane tumor necrosis factor receptor 1 positive decidual cells were 16.42 ± 7.10 Mean ± SD for women with unexplained early spontaneous abortion and 13. 14 ± 6.30 for healthy pregnant women ( P < 0.05). Serum concentration of soluble tumor necrosis factor receptor 1 was significantly higher in women with unexplained early spontaneous abortion than in healthy pregnant women and in women with threatened abortion, and no difference was found between healthy pregnant women and women with threatened abortion. Conclusion: Women with unexplained early spontaneous abortion present significantly higher expression of tumor necrosis factor receptor 1 than healthy pregnant women, suggesting that over-expression of tumor necrosis factor receptor 1 may contribute to the development of early spontaneous abortion.
基金This project was financially aided by the National"Seven-Five"Research Funds of China
文摘The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunohistochemistry(ABC),Western blot and North-ern blot technique,It was found that the expression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-Ⅰ-R was signif-icantly higher in PHC than in normal liver tissue and the expression of IGF-Ⅱ and IGF-Ⅱ-R wasremarkably higher in the juxtacancerous liver tissue from PHC patients than in PHC proper.Itwas noteworthy that the expression of IGF-Ⅱ in both the cancer proper and the juxtacancerousliver tissue was characterized by its fetal type.Besides,the expression of CSF-Ⅰ-R was signifi-cantly higher in PHC than in the juxtacancerous liver tissue.It is believed that the abnormal ex-pression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-I-R in PHC and the juxtacaneerous liver tissue might berelated to the autocrine mechanism of human PHC.
基金supported by grants from the National Natural Science Foundation of China(81270282,81070176,30600242,81170192,81200163)Wenzhou Science Technology Bureau Foundation(Y20100010)Education Foundation of Zhejiang Province(Y200906376)
文摘BACKGROUND: Retinoid X receptor(RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H2O2-induced apoptosis of H9c2 ventricular cells in rats. But the protective effect and mechanism of activating RXR in cardiomyocytes against hypoxia/reoxygenation(H/R)-induced oxidative iniury are still unclear.METHODS: The model of H/R injury was established through hypoxia for 2 hours and reoxygenation for 4 hours in H9c2 cardiomyocytes of rats. 9-cis-retinoic acid(9-cis RA) was obtained as an RXR agonist, and HX531 as an RXR antagonist. Cultured cardiomyocytes were randomly divided into four groups: sham group, H/R group, H/R+9-cis RA-pretreated group(100 nmol/L 9-cis RA), and H/R+9-cis RA+HX531-pretreated group(2.5 μmol/L HX531). The cell viability was measured by MTT, apoptosis rate of cardiomyocytes by flow cytometry analysis, and mitochondrial membrane potential(ΔΨm) by JC-1 fluorescent probe, and protein expressions of Bcl-2, Bax and cleaved caspase-9 with Western blotting. All measurement data were expressed as mean±standard deviation, and analyzed using one-way ANOVA and the Dunnett test. Differences were considered signif icant when P was <0.05.RESULTS: Pretreatment with RXR agonist enhanced cell viability, reduced apoptosis ratio, and stabled ΔΨm. Dot blotting experiments showed that under H/R stress conditions, Bcl-2 protein level decreased, while Bax and cleaved caspase-9 were increased. 9-cis RA administration before H/R stress prevented these effects, but the protective effects of activating RXR on cardiomyocytes against H/R induced oxidative injury were abolished when pretreated with RXR pan-antagonist HX531.CONCLUSION: The activation of RXR has protective effects against H/R injury in H9c2 cardiomyocytes of rats through attenuating signaling pathway of mitochondria apoptosis.
文摘Estrogen and progesterone receptor (ER and PR) contents of 40 breastcancer patients were determined with immunofluorescent staining.Thedifferentiation of cancer cells was evaluated on the basis of histological andultrastructural changes.It was found that there was a positive correlation of ERand PR contents with the cellular differentiation of breast cancer,and the lattercould be used to estimate the status of hormone receptors.Breast cancer is a malignant disease with heteropathological characteristics.In handling a breast cancerpatient,both the status of hormone receptors and the cellular differentiationshould be considered and the treatment varied with each pa(?)ent.For those witha well-differentiated cancer and rich hormone receptors,endocrine therapy shouldmainly be administered,while for those with a poorly-differentiated cancer and afew hormone receptors,chemotherapy would be of choice.
