AIM: To study the effect of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP~+)-induced glutamate uptake inhibition in C6 glioma cells. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method. RESULTS: It was shown that Group Ⅱ mGluRs agonist (2' S, 2' R, 3 ' R) -2- (2', 3 ' -dicarboxycyclopropyl) glycine (DCG-Ⅳ) (100 ?mol?L~(-1)) and Group Ⅲ mGluRs agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) (100 ?mol?L~(-1)) significantly reversed MPP~+-induced glutamate uptake inhibition. Furthermore, the enhancement effects of DCG-Ⅳ and L-AP4 were blocked by their respective antagonists, (RS)-1 -Amino-5-phosphonoinan-1-carboxylic acid (APICA) and (RS)-?-methylserine-O-phosphate (MSOP). CONCLUSION: Group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.

AIM: To study whether agonists of group II and III metabotropic glutamate receptors (mGluRs) exert effects on LPS-induced glutamate uptake inhibition in C6 glioma cells. METHODS: The glutamate uptake into C6 glioma cells was measured by uptake of [3H]-D,L-glutamate; and the apoptosis and the viability of C6 glioma cells were investigated by Hoechst33342 and MTT methods, respectively. RESULTS: LPS (4, 6 ?g/mL) inhibited glutamate uptake significantly compared with that in the control group without effect on the apoptosis and viability of C6 glioma cells. Pretreatment of C6 glioma cells with group II and III mGluRs agonists DCG-IV(100 ?mol/L) and L-AP4(100 ?mol/L) reversed LPS-induced glutamate uptake inhibition. These recovery effects were abolished by their respective antagonists APICA and MSOP. CONCLUSION: Activation of group II and III mGluRs recovers LPS-induced glutamate uptake inhibition in C6 glioma cells, suggesting the enhancement of glutamate uptake is involved in neuroprotective roles exerted by group II and III mGluRs agonists.

AIM: To study the effects of group Ⅱ and Ⅲ metabotropic glutamate receptors (mGluRs) agonists on 1-methyl-4-phenylpyridinium (MPP+) -induced glutamate uptake inhibition. METHODS: The glutamate uptake into astrocytes was measured by using radio-ligand binding assay method,and the viability of astrocytes was investigated by MTT method. RESULTS: It was shown that MPP+(150, 200 ?mol?L -1 ) inhibited glutamate uptake into astrocytes,but produced no effect on the viability of astrocytes,and the inhibition rates were 58.3 % and 70.1 %,respectively. Group Ⅱ mGluRs agonist (2'S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) ( 0.1 ,1,10, 100 ?mol?L -1 ) and Group Ⅲ mGluRs agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) (1,10, 100 ?mol?L -1 ) significantly reversed MPP+-induced glutamate uptake inhibition. CONCLUSION: MPP+ directly inhibits the function of glutamate transporters,and group Ⅱ and Ⅲ mGluRs agonists produce neuroprotective effects by enhancing the activity of glutamate transporters.

Objective:In recent years, circular RNAs (circRNAs) related to stroke has been widely studied, and its change involves multiple pathophysiological aspects of stroke, including angiogenesis, neural plasticity, cell apoptosis, and neuroinflammation. Further exploration of the changes of specific circRNAs after acute ischemic stroke and the molecular biological mechanisms involved will help to develop possible new drug targets and improve the prognosis of patients. This article reviews the main circRNAs that have changed after acute ischemic stroke, and their mechanism of action, functional detection methods, and challenges faced by the current research.

OBJECTIVETo assess the association of vitamin D receptor (VDR) gene Fok I and Bsm I polymorphisms with dyslipidemia in elderly male patients with type 2 diabetes of Han nationality.

METHODSA total of 328 elderly male residents of Han nationality in Beijing, including 237 type 2 diabetic patients and 91 healthy control subjects, were enrolled in this study. The diabetic patients were divided into non-dyslipidemia group (DO group, n=134) and dyslipidemia group (DH group, n=103). All the participants were genotyped for Fok I and Bsm I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology, and the results were compared with their clinical characteristics.

RESULTSFor Fok I, the frequency of F allele was significantly higher in the diabetic patients than in the control group (Χ(2)=3.873, P=0.049, OR=1.439, 95% CI: 1.001-2.071). In the dominant model, the frequency of FF genotype was significantly higher in the diabetic group (Χ(2)=5.057, P=0.025, OR=1.756, 95% CI: 1.072-2.875) as well as in DH group (Χ(2)=6.168, P=0.013, OR=2.06, 95% CI: 1.161-3.663) than in the control group. There was no significant differences in the genotype frequency or allele distribution in other paired groups (P>0.05). Compared with Ff + ff genotype, FF genotype was associated with a significantly decreased average diastolic blood pressure (P=0.039) but significantly increased postprandial blood glucose (P=0.035), triglycerides (P=0.049) and uric acid (P=0.031). No significant difference was detected in genotype frequency or allele distribution of Bsm I polymorphisms between the groups (P>0.05); serum creatinine levels were significantly higher in bb genotype than in BB + Bb genotype group (P=0.011).

CONCLUSIONVDR gene Fok I polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where Bsm I polymorphisms are not associated with diabetic dyslipdiemia.

Aged ; Alleles ; Blood Glucose ; Blood Pressure ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; genetics ; Dyslipidemias ; genetics ; Ethnic Groups ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Receptors, Calcitriol ; genetics ; Risk Factors ; Triglycerides ; blood

Objective:To construct a new thrombus risk assessment model and evaluate its predictive ability for venous thromboembolism(VTE)in the patients with malignant tumors,and to provide the basis for the early predition of the malignant tumor patients with high risk for VTE.Methods:A total of 128 untreated malignant tumor patients were included,of which 40 were diagnosed with VTE within 2 months of malignant tumor diagnosis and categorized as VTE group.A total of 88 patients who did not develop VTE were categorized as non-VTE group.The clinical risk factors and laboratory indicators of the patients in two groups were compared and analyzed;the types of thrombotic events of the patients were analyzed;the diagnostic values of thrombin-antithrombin-complex(TAT),α2-plasmin inhibitor-plasmin complex(PIC),D-dimer(D-dimer),and fibrin degradation products(FDP)in malignant tumors complicated by VTE were assessed using receiver operating characteristic(ROC)curve analysis;Multivariate Logistic regression analysis was used to analyze the correlations of the clinical risk factors and biomarkers with the malignant tumors complicated with VTE.A new thrombus risk assessment model was constructed,consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors.The predictive probability of the model for malignant tumors complicated by VTE was evaluated based on the significance,goodness of fit,calibration curve,and C value of the model.The clinical application value of the new thrombus risk assessment model,COMPASS-CAT risk score(CRS),and Khorana risk score(KRS)in assessing malignant tumor patients complicated by VTE was compared using the C value and decision curve analysis(DCA).Results:The plasma levels of TAT(P＜0.001),PIC(P＜0.001),D-dimer(P＜0.05),and FDP(P＜0.01)of the patients in VTE group were higher than those in non-VTE group.Compared with the patients without cardiovascular risk factors,poor differentiation,and lymphatic metastasis,the malignant tumor patients with cardiovascular risk factors(P＜0.001),poor differentiation(P＜0.001),and lymphatic metastasis(P＜0.05)were more likely to develop VTE.Most VTE events(65％)were isolated deep vein thromboembolism(DVT).The ROC curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of TAT and PIC were higher than those of D-dimer and FDP.TAT≥0.70 μg·L-1(P＜0.05),poor differentiation(P＜0.01),and cardiovascular risk factors(P＜0.01)were the independent risk factors for VTE in the malignant tumor patients.A new thrombus risk assessment model consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors was constructed.The new risk assessment model had a high goodness of fit(P=0.805)and good predictive ability during internal validation(x2=75.266,P＜0.001).The ROC curve analysis results showed that the C values for the new thrombus risk prediction model,CRS,and KRS were 0.908,0.676,and 0.541,respectively.The DCA curve analysis results showed that the new thrombus risk assessment model had a higher net benefit rate compared with CRS and KRS.Conclusion:TAT and PIC have greater diagnostic efficiency than D-dimer in the early prediction of the malignant tumor patients with high-risk VTE.For the patients included in this study,the new thrombus risk assessment model,constructed from TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors,has superior diagnostic efficiency and clinical predictive value compared with CRS and KRS.

Objective To assess the association of vitamin D receptor (VDR) gene Fok I and Bsm I polymorphisms with dyslipidemia in elderly male patients with type 2 diabetes of Han nationality. Methods A total of 328 elderly male residents of Han nationality in Beijing, including 237 type 2 diabetic patients and 91 healthy control subjects, were enrolled in this study. The diabetic patients were divided into non-dyslipidemia group (DO group, n=134) and dyslipidemia group (DH group, n=103). All the participants were genotyped for Fok I and Bsm I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology, and the results were compared with their clinical characteristics. Results For Fok I, the frequency of F allele was significantly higher in the diabetic patients than in the control group (χ2=3.873, P=0.049, OR=1.439, 95%CI:1.001-2.071). In the dominant model, the frequency of FF genotype was significantly higher in the diabetic group (χ2=5.057, P=0.025, OR=1.756, 95%CI:1.072-2.875) as well as in DH group (χ2=6.168, P=0.013, OR=2.06, 95%CI:1.161-3.663) than in the control group. There was no significant differences in the genotype frequency or allele distribution in other paired groups (P>0.05). Compared with Ff + ff genotype, FF genotype was associated with a significantly decreased average diastolic blood pressure (P=0.039) but significantly increased postprandial blood glucose (P=0.035), triglycerides (P=0.049) and uric acid (P=0.031). No significant difference was detected in genotype frequency or allele distribution of Bsm I polymorphisms between the groups (P>0.05); serum creatinine levels were significantly higher in bb genotype than in BB + Bb genotype group (P=0.011). Conclusion VDR gene Fok I polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where Bsm I polymorphisms are not associated with diabetic dyslipdiemia.

Objective To assess the association of vitamin D receptor (VDR) gene Fok I and Bsm I polymorphisms with dyslipidemia in elderly male patients with type 2 diabetes of Han nationality. Methods A total of 328 elderly male residents of Han nationality in Beijing, including 237 type 2 diabetic patients and 91 healthy control subjects, were enrolled in this study. The diabetic patients were divided into non-dyslipidemia group (DO group, n=134) and dyslipidemia group (DH group, n=103). All the participants were genotyped for Fok I and Bsm I polymorphisms in VDR gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technology, and the results were compared with their clinical characteristics. Results For Fok I, the frequency of F allele was significantly higher in the diabetic patients than in the control group (χ2=3.873, P=0.049, OR=1.439, 95%CI:1.001-2.071). In the dominant model, the frequency of FF genotype was significantly higher in the diabetic group (χ2=5.057, P=0.025, OR=1.756, 95%CI:1.072-2.875) as well as in DH group (χ2=6.168, P=0.013, OR=2.06, 95%CI:1.161-3.663) than in the control group. There was no significant differences in the genotype frequency or allele distribution in other paired groups (P>0.05). Compared with Ff + ff genotype, FF genotype was associated with a significantly decreased average diastolic blood pressure (P=0.039) but significantly increased postprandial blood glucose (P=0.035), triglycerides (P=0.049) and uric acid (P=0.031). No significant difference was detected in genotype frequency or allele distribution of Bsm I polymorphisms between the groups (P>0.05); serum creatinine levels were significantly higher in bb genotype than in BB + Bb genotype group (P=0.011). Conclusion VDR gene Fok I polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where Bsm I polymorphisms are not associated with diabetic dyslipdiemia.

Objective : To explore the expression of chemokine CXCL1 in proliferative infantile hemangioma (IH) , and to study the effect of exogenous CXCL1 on hemangioma stem cells (HemSCs) . Methods : Immunohistochemistry was used to explore the expression of CXCL1 in proliferative IH specimens.Primary HemSCs were isolated from IH tissues by CD133 magnetic beads.5 groups of CXCL1 with different concentrations(0,10,20,50 and 100 ng/ml) were co-cultured with HemSCs, and the effects of exogenous CXCL1 on HemSCs were studied by cell viability and migration experiments. Results : CXCL1 was expressed in the interstitial tissues of proliferative IH.The overall expression of CXCL1 in proliferative IH was low, but the expression of CXCL1 in the proliferative IH interstitial tissues was higher than that of the adjacent interstitial tissues.The CXCL1 positive area rate was(0.773±0.101)% in the tumor compared with(0.268±0.081)% in the adjacent tumor, and the difference was statistically significant(t=7.843,P<0.001).Exogenous CXCL1 promoted the proliferation of HemSCs, and there were statistical differences after adding different concentrations of CXCL1 to HemSCs for 24,48,and 72 h(F=14.610,P<0.001;F=14.430,P<0.001;F=5.388,P<0.01).But the exogenous CXCL1 did not affect the migration ability of HemSCs. Conclusion The expression of CXCL1 in proliferative IH interstitial tissues is higher than that in adjacent interstitial tissues, and exogenous CXCL1 promotes the proliferation of HemSCs.

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.
Humans ; RNA, Untranslated/genetics* ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; RNA, Circular ; Central Nervous System Diseases/genetics*