Possile Effect of Small Molecule in Hedysari Radix in Antagonizing Tumor Necrosis Factor Receptor 1 Based on Molecular Docking / 中国实验方剂学杂志

Objective: To study the effect of small molecule compounds of Hedysari Radix in ntagonizing tumor necrosis factor receptor type 1 (TNFR1) based on molecular docking. Method: The structure of small molecular compound of Hedysari Radix was downloaded from the chemical composition compound library of traditional Chinese medicine, and then optimized to obtain the composition compound library of Hedysari Radix. The three-dimensional structure of the inflammatory target TNFR1 (PDB ID:1TNR) was identified. After hydrotreating and anhydrating, the binding pocket residues were identified according to the literature. According to the defined target structure and binding pocket, the flexible molecular docking was conducted between the composition compound library and the target, and the score (Glide Score) was obtained. Based on the results of molecular docking, the first nine small molecular compounds of Glide Score were selected as candidate components. On this basis, the drug-likeness was analyzed, which involved small molecular compounds that meet the number of hydrogen-bonded receptors, the number of hydrogen-bonded donors, the formula weight, the number of rotatable key and the numerical range of lipo-hydro partition coefficient. Finally, the binding mode was analyzed according to pharmacokinetic parameters and complex structure of composition-target docking. Result: The residue set in the TNFR1 drug-binding pocket were identified as glutamic acid109 (Glu109), lysine 35(Lys35), alanine62 (Ala62), serine 74 (Ser74), lysine75 (Lys75), cysteine76 (Cys76), argnine 77(Arg77), glutamine82 (Gln82), threonine89 (Thr89), asparticacid91 (Asp91), argnine92 (Arg92), aspartic acid93 (Asp93), threonine 94(Thr94), valine95 (Val95), cysteine 96(Cys96), argnine104 (Arg104), tyrosine106 (Tyr106), asparagine110 (Asn110), leucine111 (Leu111), phenylalanine112(Phe112), glutamic acid 131(Glu131) and lysine132 (Lys132). Totally 43 small molecular compounds of Hedysari Radix were obtained. Five small molecular compounds, namely hedysari radix, quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin, were screened by comprehensive factors, like docking scoring. Conclusion: Quercetin, isoliquiritin, naringenin, calycosin and liquiritigenin are the effective anti-inflammatory substances of Hedysari Radix, with a great possibility of becoming TNFR1 antagonists.

The research progress of interaction between inflammatory environment and MSCs autophagy / 中国药理学通报

Mesenchymal stem cells (MSCs) can participate in the repair of various tissue and organ damage, but inflammation often exists in local repair area,and autophagy is induced. As a kind of self-regulating mechanism of cells, autophagy can not only regulate the physiological process of MSCs under inflamma-tory environment, but also work on anti-inflammatory environ-ment. This research focuses on the relations between inflamma-tory environment and MSCs autophagy's interaction and feed-back regulation, providing a train of thought for research of MSCs in inflammatory environment.

IL-6 and TNF-α promote the differentiation of human BMSCs to TFAs by mimicry inflammatory microenvironment / 基础医学与临床

Objective To observe whether BMSCs differentiate into TAFs in inflammatory microenvironment simula-ted by IL-6 and TNF-α.Methods The experiment was divided into 9 groups:the BMSCs group,the 50 ng/mL, 100 ng/mL IL-6 intervention group, the 50 ng/mL,100 ng/mL TNF-α intervention group, the 50 ng/mL IL-6+50 ng/mL TNF-α intervention group,the 50 ng/mL IL-6+100 ng/mL TNF-α intervention group,the 100 ng/mL IL-6+50 ng/mL TNF-α intervention group and the 100 ng/mL IL-6+100 ng/mL TNF-α intervention group; After continuous induction for 42 days, BMSCs cell morphology and cycle, TAFs-tagged α-SMA and FAP protein were examined by phase-contrast microscope,flow cytometry and Western blot method. Results Compared with the normal control group, the 100 ng/mL IL-6+50 ng/mL TNF-α intervention group BMSC cell proliferation was significantly promoted;G1phase decreased in proportion and S phase increased;α-SMA and FAP protein expression was signifi-cantly increased (P＜0.05).Conclusions Microenvironment simulated by the 100 ng/mL IL-6+50 ng/mL TNF-α may induce the abnormal change of the BMSCs morphological and proliferative characteristics. TAFs reference mole-cule α-SMA and FAP expression is increased.

Effect of ultrafiltration-membrane extracts of Radix Rehmanniae Praeparata on proliferation and genetic stability of bone marrow-derived mesenchymal stem cells induced by cadmium chloride / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of ultrafiltration-membrane extracts of Radix Rehmanniae Praeparata (UMERRP) on theproliferation and genetic stability of bone marrow-derived mesenchymal stem cells (BMSCs) induced by cadmium chloride (CdCl2).</p><p><b>METHODS</b>Protective effects on the proliferation, micronuclear rates, chromosome aberration rates, and apoptosis rates were observed by micronuclei test, karyotype analysis, and flow cytometry.</p><p><b>RESULTS</b>Compared with the CdCl2 group, UMERRP with different molecular weights at 0. 8 g/L could obviously promote the proliferation (P <0. 05). Compared with the control group, micronuclear rates, chromosome aberration rates, and apoptosis rates were obviously enhanced in the CdCl2 group (P <0. 05). Compared with the CdCl2 group, UMERRP with different molecular weights could obviously decreased CdCl2 induced micronuclear rates, chromosome aberration rates, and apoptosis rates (P <0. 05). Of them, BMSC micronuclear rates and chromosome aberration rates decreased most obvious in UMERRP groups with molecular weight below 10 000 (P <0. 05). The apoptosis rate decreased most obviously in UMERRP groups with molecular weight ranging 100 000 and 200 000 (P <0. 05).</p><p><b>CONCLUSION</b>UMERRP could reduce CdCl2 induced micronuclear rates, chromosome aberration rates, and apoptosis rates.</p>

Effect of IGF-1 on long-term anxiety-like behavior in rats after hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe the changes in anxiety-like behavior among rats in the recovery stage after hypoxic-ischemic brain damage (HIBD) during the perinatal period and to investigate the effect of insulin-like growth factor 1 (IGF-1) on the long-term anxiety-like behavior and its action mechanism among rats with HIBD.</p><p><b>METHODS</b>Ninety neonatal rats (7 days old) were randomly and equally divided into normal control, HIBD, and HIBD+IGF-1 groups. A neonatal rat model of HIBD was established by Rice method in the HIBD and HIBD+IGF-1 groups. The rats in the HIBD+IGF-1 group were intraperitoneally injected with IGF-1 (0.2 mg/kg) immediately after HIBD, and the other two groups were intraperitoneally injected with an equal volume of normal saline. The anxiety-like behavior was evaluated by elevated plus-maze test on postnatal days 21 and 28. The expression of tyrosine hydroxylase (TH) in the substantia nigra was measured by immunohistochemistry on postnatal days 14, 21, and 28.</p><p><b>RESULTS</b>On postnatal days 21 and 28, the open-arm time (OAT) and percentage of OAT for the HIBD and HIBD+IGF-1 groups were significantly lower than those for the normal control group (P<0.05), but there were no significant differences between the HIBD and HIBD+IGF-1 groups (P>0.05); the percentage of open arm entry showed no significant difference between the three groups (P>0.05). On postnatal day 14, there were no significant differences in percentage of TH immunostaining-positive area between the three groups (P>0.05). On postnatal days 21 and 28, the HIBD and HIBD+IGF-1 groups had significantly lower percentages of TH immunostaining-positive area than the normal control group (P<0.05), but there was no significant difference between the HIBD and HIBD+IGF-1 groups (P>0.05).</p><p><b>CONCLUSIONS</b>HIBD in the perinatal period may cause the changes in anxiety-like behavior in adolescent rats, which may be related to decreased expression of TH in the substantia nigra. Neonatally given IGF-1 cannot improve the long-term anxiety-like behavior in rats after HIBD, and it does not affect TH expression in the substantia nigra. IGF-1 may not regulate the changes in long-term anxiety-like behavior in adolescent rats.</p>

Expressions of helper T cells and regulatory T cells in peripheral blood of children with dust mite allergic asthma and their clinical significance / 中华实用儿科临床杂志

Objective To analyze the expressions of helper T cells (Th) and regulatory T cells (Treg) in peripheral blood of children with dust mite allergic asthma and their clinical significance.Methods Thirty asthmatic children with dust mite positive were included in the study as asthmatic group.Thirty healthy subjects,age and sex matched,were included as healthy control group.Peripheral blood mononuclear cells (PBMC) were isolated by densitygradient centrifugation over Ficoll-Hypaque cushions.The expressions of interferon-γ (IFN-γ),interleukin-4 (IL-4) and Foxp3 in CD4 + T cells with or without dust mite stimulation were assessed by intracellular staining and flow cytometry (FCM).The anti-inducible costimulatory molecule (ICOS),anti-CD2s or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies were added to PBMC and co-cultured for 3 days after dust mite stimulation.The expressions of Thl (CD4 + IFN-γ+ T cells),Th2 (CD4 + IL-4 + T cells) and Treg(CD4 + CD25 + Foxp3 + T cells) were analyzed.The data were analyzed by using statistical software.Results Compared with the healthy control group,in dust mite positive asthma group,the percentage of Thl cells was remarkably increased (P ＜ 0.05),while that of Treg cells was significantly decreased (P ＜ 0.05),and that of Th2 cells were not significantly different (P ＞ 0.05).Compared with nonstimulated PBMC of asthma group,the percentages of Thl and Treg had no significant variation (all P ＞ 0.05),while that of Th2 cells was notably increased (P ＜ 0.01).In the present of anti-ICOS or anti-CD2s antibodies,no significant variation were found about the percentages of Th1 and Treg (all P ＞ 0.05),while expressions of Th2 cells were significantly decreased (all P ＜0.0001).However,in the present of anti-CTLA-4 antibodies,the percentages of Th1,Th2 and Treg had no significant difference (all P ＞ 0.05).Conclusions There is a constructive,allergen independent Th1 activation and Treg deficiency as well as allergen inductivity,ICOS-and CD2s-dependent Th2 activation in the peripheral blood of children with dust mite allergic asthma.

The influence of the total flavonoids of Hedysarum polybotry on the proliferation, cell cycle, and expressions of p21Ras and proliferating cell nuclear antigen gene in erythroleukemia cell line K562 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of total flavonoids of Hedysarum polybotry on the proliferation, cell cycle, and expressions of p21(Ras) and proliferating cell nuclear antigen (PCNA) gene in erythroleukemia cell line K562.</p><p><b>METHODS</b>The effect of total flavonoids of Hedysarum polybotry on K562 cell line survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction assay. The time- and dose-dependent manner was also observed. The cell cycle and apoptosis were analyzed with flow cytometry (FCM). The immunocytochemistry method was applied to quantitatively analyze the effects of flavonoids of Hedysarum polybotry on changes p21(Ras) and PCNA gene expressions.</p><p><b>RESULTS</b>Flavonoids of Hedysarum polybotry (20-100 μg/mL) significantly inhibited the proliferation of K562 cells in a time- and dose-dependent manner. After K562 cells were cultured for 48 h, total flavonoids of Hedysarum polybotry had no significant effect on the apoptosis of K562 cells but showed significantly inhibition (P<0.01), indicating that total flavonoids of Hedysarum polybotry could induce K562 cells arrested at G(0)/G(1) and G(2)/M phases. Compared with the control group, p21(Ras) and PCNA gene expressions were decreased significantly in K562 cells treated with total flavonoids of Hedysarum polybotry (40 and 80 μg/mL, respectively) for 48 h.</p><p><b>CONCLUSION</b>The inhibitory effect on proliferation of K562 cells was observed in the groups treated with flavonoids of Hedysarum polybotry, which might be related to cells arresting.</p>

Reference values of brachial-ankle pulse wave velocity for Northern Chinese / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Brachial-ankle pulse wave velocity (baPWV) is a reliable method for measuring arterial elasticity, but the absence of reference value for baPWV has limited its wide use. We conducted an epidemical study in north China to investigate the reference value of baPWV for Chinese people and its influential factors.</p><p><b>METHODS</b>A total of 974 identified healthy subjects were recruited in this study. The values of baPWV were evaluated noninvasively with an automatic device.</p><p><b>RESULTS</b>For healthy population, the mean value of baPWV was higher for male (P < 0.001). Multiple regression analysis demonstrated that both age and systolic blood pressure were positively associated with baPWV for male and female (P < 0.001). BaPWV value was higher in male than in female in younger group (< 50 years) but not in older group (P <or= 0.001). The upper limits of baPWV were 1394/1264 cm/s, 1435/1361 cm/s, 1552/1433 cm/s, 1597/1609 cm/s and 1798/1915 cm/s for healthy male/female at 10 years interval (age range 20 - 70 years).</p><p><b>CONCLUSIONS</b>Aging is the most important reason of arterial stiffness, but the effect of age on baPWV augmentation is greater for healthy female than their male counterpart. The reference values of baPWV by sex and age are very useful for clinical and preventive medicine.</p>

An etiological study on acute respiratory infection among inpatient children in Suzhou / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the pathogen of children with acute respiratory infection (ARI) in Suzhou and to provide some evidences for clinical diagnosis and treatment.</p><p><b>METHODS</b>The nasopharyngeal secretion samples from 2492 inpatient children with ARI, during the period of November 2005 to May 2007, were investigated for respiratory syncycial virus (RSV), influenza virus A and B, parainfluenza virus type 1, 2, 3 and adenovirus by both the indirect immunofluorescence assay and virus isolation. Human metapneumovirus (hMPV) were examined by reverse-transcription polymerase chain reaction (RT-PCR) at the same time.</p><p><b>RESULTS</b>Of 2492 samples tested, 961 (38.6%) were positive. The total positive rate of virus pathogens in children with ARI was found related to age, season and respiratory disease. The detection rates by age were: 50.0% (412/824), 43.4% (190/438), 30.5% (207/679)and 27.6% (152/551), chi(2) = 96.5002, P < 0.01; the detection rates by season were : 46.7% (366/784), 13.8% (66/478), 13.8% (59/428) and 58.6% (470/802), chi(2) = 392.3279, P < 0.01; the detection rates by disease were (acute upper respiratory infection, acute laryngitis, throat-trachea-bronchitis, bronchial pneumonia, pneumonia genuine, bronchiolitis, bronchial asthma): 21.4% (30/140), 73.7% (14/19), 32.0% (8/25), 36.9% (598/1620), 13.1% (8/61), 66.1% (216/327) and 29.0% (87/300), chi(2) = 162.1276, P < 0.01. There was no association between the total positive rate and sex. The detection rates by sex were: 39.0% (588/1508) for male and 37.9% (373/984) for female, chi(2) = 0.2962, P > 0.05. The peak of RSV appeared from December to March. There was the highest RSV detection rate 50.2% (164/327) with bronchiolitis. The hMPV can be detected all year around. The peak of hMPV appeared in winter and the detection rate was 13.2% (106/802).</p><p><b>CONCLUSION</b>RSV and hMPV are the main respiratory viral pathogens in Suzhou. Detection of viral pathogens in children with respiratory infection could give fast, accurate diagnostic evidence, and help avoid antibiotics abuse.</p>

Detection and Analysis of Bacteria Producing Extended Spectrum ?-Lactamases in Children with Lower Respiratory Tract Infection / 实用儿科临床杂志

Objective To understand the status and drug resistant patterns of strains of extended spectrum ?-lactamase(ESBLs) in children with lower respiratory tract infection,and to give clinical suggestions for rational treatment.Methods Escherichia coli and klebsiella pneumoniae were isolated from the 2 969 nasopharyngeal secretions which collected from lower respiratory tract of children in our hospital from Jan.2006 to Dec. 2007.Dual-sheets and sheets-diffusing method (K-B method) were used to determine the ESBLs and antibiotic susceptibility was tested by K-B method which included 18 kinds of antibiotics,the results were marked by resistant,intermedial and sensitive.Chi-square test was used to analyze the data.Results Total 135 strains were detected,73 strains were escherichia coli,of which 54 strains(74.0%)produced ESBLs,62 strains were klebsiella pneumoniae,of which 33 strains(53.2%)produced ESBLs.The 2 bacterias were found more in children with 1-6 months old than those in other age groups,the ratio of which were 50 strains and 41 strains,respectively (Pa0.05).The resistant rate of ESBLs-producing strains to penicillins,cephalosporins,quinolones,aminoglycosides and sulfamido was higher than that of non ESBLs-producing strains respectively.And the resistant rates to beta-lactam antibiotics of ESBLs strains were located on a high level.Whether producing ESBLs or not,the 2 bacterias were still sensitive to amikacin,cefoxitin,cefoperazone/sulbactam and imipenem.Conclusions The prevalences of ESBLs-producing escherichia and klebsiella pneumonia were high.There was a multi-drug resistance to the varied antibiotics.It is very important to make sputum culture and use sensitive antibiotics in treatment according to drug sensitivity test to control the occurrence and conveying of the ESBLs.