Research progress on natural cannabinoid receptor type 2( CB2R)regulators and their effects on bone metabolism / 中国中药杂志

Cannabinoid receptor type 2( CB2 R),a member of the G protein-coupled receptor( GPCR) superfamily,has a variety of biological activities,such as regulating pain response,resisting inflammation and fibrosis,and mediating bone metabolism. Some CB2 R regulators exhibit a good regulatory effect on bone metabolism. Cannabinoids in Cannabis sativa can cause psychoactive effects despite various pharmacological actions they exerted by targeting CB2 R. Therefore,it is of great significance to discover CB2 R regulators in non-Cannabis plants for finding new lead compounds without psychoactive effects and elucidating the action mechanism of plant drugs. The present study clarifies the discovery,structure,and physiological functions of CB2 R,especially its regulatory effects on bone metabolism,summarized CB2 R regulators extracted from non-Cannabis plants,and systematically analyzes the regulatory effects of CB2 R regulators on bone metabolism in animals,osteoblasts,and osteoclasts,to provide a scientific basis for the discovery of new CB2 R regulators and the development of anti-osteoporotic drugs.

Analysis on Mechanism of Astragali Radix in Treating IgA Nephropathy Based on Network Pharmacology and in Vitro Cell Experiment / 中国实验方剂学杂志

Objective:To explore the multi-component， multi-target and multi-pathway mechanism of Astragali Radix against immunoglobulin A nephropathy （IgAN） by network pharmacology， aiming to provide evidence for its basic research and clinical application. Method:The active chemical components and targets of Astragali Radix and targets associated with IgAN were obtained by literature mining and GeneCards， Traditinal Chinese Medicine Integrated Database （TCMID）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. Cytoscape 3.7.1 software was used to draw network interaction diagrams. The key targets of Astragali Radix against IgAN were searched by network topology. Gene ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis involved in the targets were analyzed by different packages in R programming language. On this basis， cell experiments <italic>in vitro</italic> were carried out to verify the activation effect of astragaloside Ⅳ on phosphatidylinositol 3-kinase/protein kinase B/tumor suppressor gene protein 53 （PI3K/Akt/p53） signaling pathway of human mesangial cells. Result:A total of 25 active components and 49 ingredient-disease targets of Astragali Radix were screened. The GO enrichment analysis included 84 items， which were related to nuclear hormone receptor binding， nuclear receptor activity， deoxyribonucleic acid binding transcriptional activation activity and other aspects. The KEGG pathway enrichment analysis included 88 KEGG pathways， which were closely related to PI3K/Akt signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， advanced glycation end product/receptor of advanced glycation end product （AGE/RAGE） signaling pathway and others. Cell experiments <italic>in vitro </italic>confirmed that astragaloside Ⅳ could effectively inhibit the platelet derived growth factor-BB （PDGF-BB）-induced proliferation of human mesangial cells by regulating PI3K/Akt/p53 signaling pathway. Conclusion:The active ingredients of Astragali Radix may play a role in the treatment of IgAN by acting on targets and pathways related to apoptosis， oxidative stress， inflammation response and others， providing ideas and directions for the new drug development and mechanism study of IgAN.

Study on the Correlation between GRIN2B Gene Polymorphism and Han Population with Epilepsy in South Fujian / 中国药房

OBJECTIVE：To investigate the correlat ion betwe en N-methyl-D-aspartate（NMDA）receptor subunit gene GRIN2B polymorphism and Han population with epilepsy in south Fujian. METHODS ：In retrospective study ，167 healthy people who had physical examination in the Affiliated Dongnan Hospital of Xiamen University were selected from Jan. 2017 to May 2018 as control group；163 epileptic patients who were monitored the blood concentration of sodium valproate were selected as epilepsy group. The clinical data and peripheral blood of 2 groups were collected. 12 loci of GRIN2B genotype（rs11055514，rs11055515，rs12814951， rs74816802，rs2160517，rs2193149，rs966664，rs1805476，rs1806201，rs1805522，rs3764030，rs1019385） in subjects were genotyped. Haploview 4.2 software was used to perform linkage disequilibrium （LD）analysis，and Pearson correlation was used to analyze haplotype. Distribution differences of wild homozygote （AA），mutant heterozygote （Aa）and mutant homozygote （aa） genotypes at 12 loci of GRIN2B gene between 2 groups were analyzed statistically by using GENO ，TREND，DOM and REC. Logistic regression model was used to analyze the correlation of epilepsy induction among 12 loci of GRIN2B gene. RESULTS ： Totally 12 loci of GRIN2B gene were all in line with Hardy-Weinberg equilibrium in 2 groups（P＞0.05）. There was an obvious LD phenomenon between the block 1 composed of rs 11055514，rs11055515，rs12814951，rs74816802，rs2160517，rs2193149 and rs966664 and the block 2 composed of rs 3764030 and rs 1019385（D’＞0.9，r2＞1/3）. There was a correlation between CGGACAG monoploid in block 1 and the occurrence of epilepsy （P＜0.05）. There was statistical significance in the distribution difference of rs74816802 and rs 2193149 between 2 groups（P＜0.05）. The mutation of rs 2193149 locus may cause epilepsy （addition and effect of alleles ：OR＝1.529，L95＝1.017，P＝0.041）. CONCLUSIONS ：The mutation of GRIN2B gene rs 2193149 locus may be one of the risk factors of epilepsy in Han population from south Fujian.

Effects of Sodium Valproate on the Expression of FAK in Hippocampus of Rats with Seizure Induced by Pentylenetrazole / 中国药师

Objective: To investigate the effects of sodium valproate (VPA) on the expression of FAK and FAK-pY397 in hippo-campus of rats with seizure induced by pentylenetetrazole (PTZ). Methods: A total of 75 rats were randomly divided into 5 groups:the normal control group, the epilepsy model group (PTZ group) and the VPA groups(150,300 and 600 mg·kg-1·d-1)with 15 ones in each group. The model rats were continuously given PTZ (32 mg·kg-1·d-1) by intraperitoneal injection for 4 weeks and paid close attention to the behavioral changes, and then VPA was administrated orally for 2 weeks. The pathological changes of hippo-campus tissue were observed by HE staining. The expressions and distributions of FAK, FAK-pY397 and integrin in serum and hippo-campus were evaluated by immunohistochemical assay and enzyme-linked immunosorbent assay (ELISA). Results: Compared with the model group, the symptoms of epilepsy in VPA groups were significantly relieved and cell apoptosis was improved. Immunohistochemis-try showed that the expression of FAK-pY397 decreased significantly in VPA groups with the increase of sodium valproate dose, and there was no significant difference in the expression of ITGα3. The VPA groups significantly reduced the expression of FAK, FAK-pY397 and ITGβ1(P<0. 05), the expression of FAK and ITGβ1 protein in peripheral serum decreased significantly (P<0. 05), but the expression of FAK-pY397 did not change significantly. Conclusion: VPA can effectively participate in or affect the process of epi-lepsy by inhibiting the expressions of FAK-pY397 and ITGβ1 in hippocampal tissue of epileptic rats.

Effects of 16 week aerobic exercise on baPWV and ABI of middle-aged and elderly patients / 中国应用生理学杂志

OBJECTIVES@#To investigate the interventional effects of 16-week aerobic exercises on the elderly's arteriosclerosis and its mechanism.@*METHODS@#Twenty-seven elderly people with the average age of 62. 70 ±3. 26 joined a 16-week square dance/taijiquan exercise program that conducted 60 minutes each time, six times per week. Arterial stiffness and its related indexes such as systolic pressure(SBP), diastolic pressure(DBP), left brachial-ankle pulse wave velocity (L-baPWV), right brachial-ankle pulse wave velocity(R-baPWV), left ankle brachial index (L-ABI), right ankle brachial index(R-ABI), serum triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-c), low density lipoprotein cholesterol(LDL-c), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione peroxidase (GSH-Px) were detected at 3 time points including before exercise program, by the end of exercise for 8 weeks and 16 weeks.@*RESULTS@#① Compared with pre-exercise, the R-baPWV and R-ABI of the elderly people were decreased at the end of the 8 week, and the L-baPWV, RbaPWV, R-ABI and L-ABI were decreased significantly at the end of the 16 week. ②Compared with pre-exercise, SBP and DBP were declined markedly (<0.01, <0.05) at the end of the 8 week, SBP, DBP and pulse pressure were decreased significantly (<0.01, <0.05) at the end of the 16 week. ③Compared with pre-exercise, TC and LDL-c were declined markedly (<0.01) at the end of the 8 and the 16 week, and there was no difference of the level of TG and LDL-c between pre-exercise and post-exercise. ④There was no evident difference of serum level of SOD, GSH-Px, MDA between pre-exercise and post-exercise at the end of the 8 week. Compared with pre-exercise, the level of serum SOD, GSH-Px was increased evidently while the content of serum MDA was decreased significantly (<0.01).@*CONCLUSIONS@#Sixteen-week aerobic exercises could reduce baPWV and ABI levels, regulate blood pressure, blood lipids and lipid peroxides levels of the elderly evidently, thus improve the controlling quality of atherosclerosis.

Research Progress in Focal Adhesion Kinase Used for Neurological Diseases / 中国药师

Focal adhesion kinase ( FAK) is one of novel non-receptor protein tyrosine kinases critical for the dynamic regulation of cell adhesion structures,which is activated through the phosphorylation of its tyrosine residue by ligands that bind to integrins. Some studies have demonstrated that FAK has close relationship with nervous system development, synaptic plasticity and the occurrence and development of nervous system diseases. The review summarized the functions of FAK in neurological diseases.

Research Progress in Focal Adhesion Kinase Used for Neurological Diseases / 中国药师

Focal adhesion kinase ( FAK) is one of novel non-receptor protein tyrosine kinases critical for the dynamic regulation of cell adhesion structures,which is activated through the phosphorylation of its tyrosine residue by ligands that bind to integrins. Some studies have demonstrated that FAK has close relationship with nervous system development, synaptic plasticity and the occurrence and development of nervous system diseases. The review summarized the functions of FAK in neurological diseases.

Correlation of ATP Binding Cassette Transporter A1 Gene Polymorphisms and Lower Extremity Athero-sclerotic Disease / 中国药师

Objective:To analyze the correlation of single nucleotide polymorphisms ( SNP) of ATP binding cassette transporter A1 gene (ABCA1) and lower extremity atherosclerotic disease (LEAD). Methods: The clinical data and peripheral blood were col-lected from 630 participants (314 LEAD cases and 316 normal controls) in Han population of Minnan. The 9 SNP genotypes in the ABCA1 gene were detected by Sequenom MassArray. Results:Among the 9 SNP genotypes, rs2980083 was rejected because it wasn' t in accordance with Hardy-Weinberg equilibrium. Obvious linkage disequilibrium was found between rs2066714 and rs2066715, rs1800976 and rs2246293, rs2246293 and rs2980083, and rs1800976 and rs2980083(D′>0. 9,r2 >1/3). There were no significant differences (P>0. 05) in 6 haplotypes of ABCA1 gene groups between the LEAD cases and the normal controls. No significant differ-ences (P>0. 05) were found in frequency distribution between the LEAD cases and the normal controls in 8 SNP according to the re-sults of genotype statistics. There was no onset risk of LEAD according to the gene logistic regression analysis. Conclusion:The SNPs of rs10124755, rs2980083, rs1800976, rs4149341, rs2066714, rs2066715, rs2066716, rs2230808 and rs2246293 might not correlate with the susceptibility of LEAD in Han population of Minnan.

Clinical analysis and autoimmune regulator gene mutation of autoimmune polyendocrinopathy syndrome type I in a family: a report of one case / 中国当代儿科杂志

The clinical data of one patient with autoimmune polyendocrinopathy syndrome type I were collected. PCR-DNA direct bidirectional sequencing was applied for mutation screening of 14 exons in autoimmune regulator (AIRE) gene in the patient and her parents. A total of 50 unrelated healthy controls were selected and tested. The bioinformatic methods were used to predict the possible impact of the mutations on the structure and function of the AIRE protein. The results of sequencing showed that heterozygous mutation c.622G>T (p.G208W) in exon 5 of the AIRE gene was detected in the patient and was a novel mutation, which had not been reported in the HGMD database and latest articles. This mutation was not detected in the 50 unrelated normal controls. The novel mutation of c.622G>T (p.G208W) in AIRE gene might play an important role in the pathogenesis of this case of autoimmune polyendocrinopathy syndrome type I.

The relationship among the matrix metalloproteinase-3,carotid artery plaque and ischemic cerebrovascular disease / 中国医师杂志

Objective To investigate the relationship between the matrix metalloproteinase-3(MMP-3)and the stability of carotid artery plaque,and explore MMP-3's prediction role on the attack and relapse of acute ischemic cerebrovascular events.Methods 100 patients with the first ever acute cerebral infarction,100 patients with chronic cerebral circulation insufficiency(CCCI)and 40 persons without cerebrovascular diseases were enrolled in this study.According to the carotid ultrasound examination,100 cerebral infarction patients were divided into three subgroup: unstable plaque group(45 patients,mixed plaque,soft plaque),stable plaque group(35 patients,plaque Group)and endometrial coarse group(25patients).Matrix metalloproteinase-3(MMP-3)levels of all the subjects were measured by enzyme-linked immunosorbent assay(as basal level).All the subjects were followed up for one year to observe cerebral infarction events.Serum MMP-3 levels of each group,and the basic serum MMP-3 levels were compared among patients who were attacked or relapsed cerebral ischemic with those who had not been attack cerebral ischemic during this period of time.Results 5 patients in the cerebral infarction group had relapse (5%),2 patients in the CCCI group were attacked by cerebral ischemic(2%),and no one in the normal control group was attacked by cerebral ischemic.Serum MMP-3 levels in the acute cerebral infarction group were significantly higher than CCCI group,and both groups were significantly higher than normal control group (P ＜0.05).The basic serum MMP-3 levels in all patients who were attacked by cerebral ischemic were significantly higher than those who had not been attack by cerebral ischemic during this period of time(P ＜0.05).The serum MMP-3 levels of the unstable plaque group were significantly higher than stable plaque group.And both groups were significantly higher than endometrial coarse group(P ＜0.05).Conclusions Elevated levels of matrix metalloproteinase-3(MMP-3)might have something with the stability of carotid atherosclerotic plaque,and participate the attack and the relapse of acute cerebral infarction.Determination of MMP-3 might be used to predict the attack and relapse of acute cerebral infarction.

Separation and purification of flavonoids from Smilax glabra by macroporous adsorption resin / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the process of separating and purifying flavonoids from Smilax glabra.</p><p><b>METHOD</b>With the yield of flavonoids as index, the optimum process of separating and purifying flavonoids from S. glabra Roxb was screened by static and dynamic adsorption tests.</p><p><b>RESULT</b>The static saturated adsorption capacity of D101 macroporous resin to flavonoids of S. glabra was 45.6 mg x g(-1) (dry resin). The optimum conditions of dynamic adsorption and elution were as that the pH, the concentration, the adsorption velocity of the extracting solution, and the adsorption capacity were 6.00 +/- 0.20, 4.2 mg x mL(-1), 2 mL x min(-1) and 15 mL, respectively. The adsorbed resin column was washed by 100 mL 60% ethanol with pH value of 8.00 +/- 0.20 at the eluting velocity of 3 mL x min(-1) after washed by 100 mL distilled water.</p><p><b>CONCLUSION</b>The flavonoids of S. glabra was able to be easily separated and purified by D101 macroporous resin under the optimum conditions above, and the recovery rate was higher than 90%. The content of obtained flavonoids reached 62.6%, which was 2 times of the content before purification.</p>

Relationship between iron overloading and heme oxygenase-1 after rat intracerebral hemorrhage / 中华老年医学杂志

Objective To investigate whether iron mass induces HO-1 overexpression and explore the role of HO-1 in rat intracerebral hemorrhage(ICH). Methods In this study,144 hydrated chloride aldehyde-anesthetized Sprague- Dawley rats were used,autologous blood were injected into the right caudate nucleus to establish the ICH model.Saline injection and health were served as controls.Deferoxamine(DFO)with an intraperitoneal injection served as intervention group.Enhanced Perl's reaction was used for iron staining and brain iron deposits were determined.Brain HO-1 level were examined by immunohistochemical analysis and reverse transcription polymerase chain reaction(RT-PCR). Results There was a 21-fold increase in iron deposits around the hematoma 7 days after the infusion of 100 μl of autologous blood.Markedly increased levels of perihematomal HO-1 immunoreactivity and HO-1 mRNA in all ICH rats were detected at 3-14 days.The addition of DFO significantly reduced iron deposits in the ipsilateral basal ganglia at 7-14 days after ICH.DFO also inhibited HO-1 overexpression at day 7,14.Correlations test showed that there were positive correlations of iron sediments with HO-1mRNA(r=0.647)and HO-1 immunopositive cells(r=0.209). Conclusions ICH causes iron accumulation in the brain.Iron overloading may induce HO-1 upregulation after ICH.Ratherly,the HO-1 moderate increasing possibly fits with the events,whereas HO-1 overexpression may result in its dysfunction.It may be prudent to intervene ICH with HO-1 inhibitor.

Effect of dexamethasone on peroxisome proliferator activated receptor-gamma mRNA expression in 3T3-L1 adipocytes with the human recombinant adiponectin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The fat derived protein adiponectin plays an important role in the regulation of glucose metabolism. The aim of this study was to provide the experimental basis for further investigating on adiponectin (ADPN) function. Its eukaryotic recombinant was constructed and expressed in precursor cells of 3T3-L1 adipocytes. The effects of dexamethasone on peroxisome proliferator activated receptor-gamma (PPAR-gamma) mRNA expression in 3T3-L1 cells with human recombinant adiponectin were assessed.</p><p><b>METHODS</b>The recombinant plasmid pMD18-T-hADPN and eukaryotic expression vector pcDNA3.1(+) were digested by two restrictive endonucleases and adiponectin and linear pcDNA3.1(+) were obtained. Then, they were ligated and translated into JM109. The recombinant pcDNA3.1(+)-hADPN so obtained was identified by digestion by restrictive endonuclease and nucleotide sequencing. The 3T3-L1 precursor cells were transfected using SuperFect Transfection Reagent (Qiagen). Furthermore, 3T3-L1 cells with human recombinant adiponectin incubated with dexamethasone (0.5 mmol/L) for 24 hours, cells were collected and total RNA was extracted. The PPAR-gamma mRNA expression was quantified by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>After eukaryotic recombinant was digested by Hind III and EcoR I, fragments of 800 bp and 5.4 kb were identified by nucleotide sequence scanning and consistent with theoretical values. Electrophoretogram of RT-PCR in 3T3-L1 precursors showed only one band in front of 250 bp, which was consistent with theoretical value 234 bp. In the 3T3-L1 cells, 3T3-L1 cells with plasmid and 3T3-L1 cells human recombinant adiponectin, treatment with dexamethasone (0.5 mmol/L) decreased PPAR-gamma mRNA expression compared to untreated controls (P < 0.01). Effect of dexamethasone on PPAR-gamma mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin.</p><p><b>CONCLUSION</b>The 3T3-L1 cells stably transfected human recombinant adiponectin had increased PPAR-gamma mRNA expression. Dexamethasone suppressed PPAR-gamma mRNA expression in the 3T3-L1 cells. Effect of dexamethasone on PPAR-gamma mRNA expression in 3T3-L1 cells was reversed by stably transfected human recombinant adiponectin.</p>