Application of multidisciplinary team teaching in the training of professional postgraduate students in neurology / 中华医学教育探索杂志

For the issues including inadequate ability for clinical diagnosis and treatment during the training of professional postgraduate students in neurology, this article elaborates on the importance of the application of multidisciplinary team (MDT) teaching from the aspects of the necessity of MDT teaching in the training of professional postgraduate students in neurology and the implementation scope, implementation process, implementation examples, and preliminary teaching results of MDT teaching, so as to provide experience for improving the clinical diagnosis and treatment ability of professional postgraduate students in neurology.

Co-delivery of Tim-3 mAb and sorafenib enhanced chemoimmunotherapy for hepatocellular carcinoma using "responsive shell-peeling" mesoporous silica nanoparticles / 药学学报

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3+CD4+ cells, CD3+CD8+ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Effect of Different Nitrogen Forms and Concentrations on Yield and Quality of Fritillaria thunbergii / 中国实验方剂学杂志

Objective:To investigate the effect of different nitrogen forms and concentrations on yield and quality in Fritillaria thunbergii，and provide basis for improving scientific utilization of nitrogenous fertilizer and its introduction to Chongqing area. Method:The pot culture experiment was conducted to investigate the changes in growth，physiological and biochemical characteristics，soil factors，alkaloid content and yield of Fritillaria thunbergii under the ratio of nitrate nitrogen（NO3--N） to ammonium nitrogen（NH4+-N）of 15∶0（N1），12∶3（N2），7.5∶7.5（N3），3∶12（N4） and 0∶15（N5）. Result:As compared with no-nitrogen（CK） treatment group，the growth and quality of F. thunbergii were significantly improved by different nitrogen nutrition treatments，with differences among them.With the increase of ammonium nitrogen concentration：①plant height and the activity of superoxide dismutase（SOD） reached the maximum when the ratio of NO3--N to NH4+-N was 3∶12，increased by 9.27% and 206.62% respectively compared with the CK group，② the length and width of leaf，stem diameter，chlorophyll a，chlorophyll b，total chlorophyll content，the content of available P and organic matter，total alkaloid content and yield reach the maximum when the ratio of NO3--N to NH4+-N was 0∶15，increased by 14.02%，16.44%，13.68%，40.75%，45.31%，41.72%，77.70%，14.70%，24.61%/47.39% respectively compared with the CK group，with the increase of nitrate nitrogen concentration，③the leaf index，soluble protein content，peimisine content/yield，yield of peiminine and dry weight of bulbs reached the maximum when the ratio of NO3--N to NH4+-N was 7.5∶7.5，increased by 2.54%，5.92%，21.76%/54.55%，60.61% and 26.93%，respectively compared with the CK group，④the content of carotenoids，pigment and peiminine，the activity of peroxidase（POD） and catalase（CAT），the content/yield of peimine，both peimine and peiminine，both peimine，peiminine and peimisine，dry weight of bulbs reached the maximum when the ratio of NO3--N to NH4+-N was 12∶3，increased by 45.39%，45.31%，36.01%，271.38%，67.45%，39.82%/64.87%，38.90%/63.80%，37.03%/61.57%，20.29% respectively compared with the CK group. Conclusion:All the results indicated that a higher proportion of NH4+-N is beneficial to the growth of F. thunbergii，while NO3--N is beneficial to the accumulation of alkaloids and the growth of bulbs.Therefore，the combined application of ammonium and nitrate（NO3--N to NH4+-N ratio of 12∶3） is more effective than pure nitrate or pure ammonium applications to improve the yield and quality of F. thunbergii．

Correlation Analysis Between Bulb Quality and Rhizosphere Soil Factors of Fritillaria taibaiensis / 中国实验方剂学杂志

Objective::To explore the correlation between bulb quality and rhizosphere soil factors of Fritillaria taibaiensis of different origins and years, in order to provide theoretical basis for the high quality and safe production of F. taibaiensis. Method::Totally 11 samples of bulb and rhizospheric soil of F. taipaiensis of different origins and years were taken as the research objects. Available N, available P, available K, organic matter, pH and six soil enzyme activities in rhizosphere soils were determined by soil agrochemical analysis method. Peimisine and nine nucleosides in F. taibaiensis bulbs were determined by HPLC, and total alkaloid content was determined by UV. SPSS 22.0 software was used to analyze the correlation of the measured data. Result::There were significant differences in rhizosphere soil factors and bulb quality between F. taibaiensis of different origins and years (P<0.05). In terms of soil factors, the contents of available N, available K, organic matter and six soil enzyme activities in rhizosphere soil of wild varieties were higher than those of cultivated varieties, while the contents of available P and pH were lower than those of cultivated varieties. With the increase of growth years, the soil nutrient index of cultivated varieties showed different change trends, while that of wild varieties did not change significantly. However, most of the soil enzymes in both groups decreased in varying degrees. In terms of bulb quality, the contents of nine nucleosides and alkaloids in F. taibaiensis bulbs decreased with the increase of growth years, with larger change trends of cultivated varieties, while that of wild varieties was not significant. The contents of nucleosides and alkaloids in most cultivated varieties were higher than those in wild varieties. The correlation analysis showed certain correlations between soil factors in rhizosphere as well as soil factors and bulb quality. In general, soil nutrient status and bulb quality decreased with the increase of years. Conclusion::The quality of F. taibaiensis is mainly affected by its rhizosphere soil factors. In the process of field conservation and artificial cultivation, attention shall be paid to increase or decrease of the content of soil nutrients and their proportional relationship according to actual situations, so as to ensure the quality of F. taibaiensis.

Protein interactome analysis of iduronic acid-containing glycosaminoglycans reveals a novel flagellar invasion factor MbhA.

Pathogens are able to exploit specific glycosaminoglycans (GAGs), especially iduronic acid (IdoA)-containing GAGs, to invade the host. By analyzing Escherichia coli proteome chip data, we identified the interactomes of three IdoA-containing GAGs: heparin, heparin sulfate (HS), and chondroitin sulfate B (CSB). Using non-IdoA-containing GAG, chondroitin sulfate C, as a negative control, 157 proteins specifically binding with IdoA-containing GAGs were revealed in the present study. These proteins showed functional enrichment in protein synthesis and metabolism. Fifteen proteins which commonly interacts with three IdoA-containing GAGs were further examined. The regular expression for motif showed these common IdoA interactome shared a conserved sequence. Among them, we identified a second flagellar system outer membrane protein, MbhA. The MbhA has Kd values of 8.9 × 10-8 M, 5.3 × 10-7 M, and 1.79 × 10-7 M to interact with heparin, HS, and CSB, respectively. Using flow cytometry, we confirmed that the MbhA protein can bind to human epithelial cells HCT-8. Overexpression of mbhA increased the percentage of invasion in E. coli which lacks a second flagellar system. Moreover, pre-blocking of HCT-8 cells with MbhA inhibited the bacterial invasion, implying the importance of the direct interaction of MbhA and the host cell surface on bacterial invasion. SIGNIFICANCE: We analyzed the Escherichia coli proteomic data to elucidate the interactomes of three different IdoA-containing GAGs (heparin, HS, and CSB) because these IdoA-containing GAGs can mediate bacterial invasion to the host. Through proteomic and systematic analysis, a second flagellar system outer membrane protein, MbhA, was also identified in the present study. Affinity assay confirmed that MbhA can bind to three IdoA-containing GAGs heparin, HS, and CSB. The result of flow cytometry also showed MbhA can interact with human epithelial cells HCT-8. Results of bacteria invasion assay showed overexpression of mbhA promoted the bacterial invasion. Moreover, pre-blocking of HCT-8 cells with MbhA also reduced the percentage of bacterial invasion. These findings correspond well that MbhA is one of invasion factors.

Alternaria yunnanensis sp. nov., a New Alternaria Species Causing Foliage Spot of Rubber Tree in China

A new species of Alternaria causing leaf spots on the rubber tree (Hevea brasiliensis) in Yunnan, China, was isolated, examined, and illustrated. Morphologically, it belongs to the section Porri of Alternaria, which produces relatively large conidia and a simple or branched, filamentous long beak. It is, however, characterized by conidiophores gradually enlarging near the apex into a clavate conidiogenous cell and long ellipsoid to obclavate, smooth-walled conidia with a long filamentous beak. Molecular phylogenetic analyses based on ITS rDNA, GAPDH, and TEF1-alpha sequences demonstrate that the phytopathogen falls in the clade of the section Porri, being most closely related to A. sidae, A. sennae, A. deseriticola, A. cyamopsidis, A. rostellata, A. nitrimali, A. crassa, and A. thunbergiae.

Variation Pattern of Rhizospheric Soil Nutrient for Fritillaria taipaiensis / 中国实验方剂学杂志

Objective: To study the variation patterns of rhizospheric soil nutrient and the content of nutrient elements for Fritillaria taipaiensis,in order to provide the theoretical base for the soil improvement and balanced fertilization during the artificial cultivation. Method: Totally 14 samples of rhizospheric soil of Fritillaria taipaiensis from different origins and years were taken as the research objects. Total N,available N,total P,available P,total K,available K,organic matter,pH and 7 nutrient element contents (Ca,Mg,Na,Mn,Zn,Cu and Ni) were analyzed by the soil agrochemical analysis method combined with the atomic absorption spectrophotometry. SPSS 22.0 software was applied for data multiple comparison and correlation analysis. Result: The all results showed significant differences (PF. taipaiensis. The content of total N,available N,total P,available P and organic matter of rhizospheric soil collected from cultivated varieties decreased with the increase of years,and the content of total K,available K and pH decreased first and then increased. However,the soil physical and chemical properties of wild varieties had no obvious change with the increase of years. The content of Ca,Mg,Na and Cu of soil from cultivated varieties decreased with the increase of years,while the content of Mn decreased first and then increased. And Zn and Ni showed no significant change with the increase of years. Compared with cultivated varieties,the content of Ca,Mg,Na,Mn and Cu increased first and then decreased. The content of Zn and Ni showed no obvious change. In general,the rhizospheric soil nutrient and the content of nutrient elements for wild F. taipaiensis were superior to those of cultivated varieties. Conclusion: The third year is the turning point of F. taipaiensis growth. The rhizospheric soil nutrient and the content of nutrient elements decreased obviously after three years. Attention shall be given to the balanced fertilization,the improvement of soil quality and the prevention of the cropping during cultivation of F. taipaiensis.

Etiologyical Analysis of 133 Patients with Elderly Macrocytic Anemia and Diagnostic Significance of Laboratory Tests / 中国实验血液学杂志

OBJECTIVE@#To study the etiology of macrocytic anemia in elderly patients and to evaluate the diagnostic significance of laborotory tests.@*METHODS@#133 elderly macrocytic anemia patients, whose age>60 years old, hemoglobin100 fL, and bone marrow cell test was performed, and these patients were grouped according to diseases, and the bilirubin, lactate dehydrogenase, folic acid, vit B12 and serum ferritin were tested, then the results of tests were compared and analyzed.@*RESULTS@#The majority of the cases were diagnosed as megaloblastic anemia (MA), myelodysplasia syndrome (MDS), acute leukemia/multiple myeloma (AL/MM) and hemolytic anemia (HA). Usually HA was a simple anemia, while others were accompanied by decrease of other 1 or 2 series. HA patients were often with significant high level of well volume (MCV), red cell distribution width(RDW), reticulocytes (RC) and indirect bilirubin (IBIL) (P<0.01). However, MA patients were often with high level of LDH. Serum ferritin (SF) level was significantly higher in both MDS and AL/MM groups (P<0.01).@*CONCLUSION@#Common causes of macrocytic anemia in elderly patients are MA, MDS, AL/MM and HA. The combination detection of MCV, RDW, RC, LDH, IBIL and SF contributes to enhancing the accuracy of diagnosis.

Correlation between rhizospheric microorganisms distribution and alkaloid content of Fritillaria taipaiensis / 中国中药杂志

In order to reveal the relationship between the amount of soil microorganisms and the quality of Fritillaria taipaiensis, both cultivated and wild F. taipaiensis were collected from Chongqing, Wuxi at different stages of their growth as objects of the research. The mycorrhizal infection rate and colonization intensity, peimisine and total alkaloid content in bulbs, the amount of microorganisms and biomass carbon content in rhizospheric soil were all determined using common methods. The results showed that the typical arbuscular-vesicle roots were formed after the AM fungi infected the F. taipaiensis roots which were collected from different origins. The mycorrhizal infection rates were ranged from 78.74% to 98.68% and the colonization intensities were ranged from 13.29% to 37.06%. The rhizospheric microorganisms of F. taipaiensis showed abundant resources. The distribution rule of them in the rhizospheric soil was as follows: the amount of bacteria>the amount of actinomycetes>the amount of fungi. The rhizospheric bacteria, decomposition inorganic phosphorus bacteria, decomposition organic phosphorus bacteria, actinomycetes amount and the total number of microbes increased first and then decreased with the increase of years, while decomposition potassium bacteria showed decreasing trend and fungi showed gradual increasing trend. The soil microbial flora content in the soil changed from "bacterial type" with a high fertility to "fungal type" with a low fertility. The mass fraction of peimisine and total alkaloid content increased first and then decreased with the increase of over the years, the same trend of culturable rhizosphere soil bacteria and actinomycetes indicated that the growth years affected the quality of soil and medicinal materials on different levels. Therefore, the diversity of microbial communities in rhizosphere soil reduced with the increase of years leading to the continuous cropping obstacles and the destruction of medicinal quality of F. taipaiensis.

Blockade of Endogenous Angiotensin-(1-7) in Hypothalamic Paraventricular Nucleus Attenuates High Salt-Induced Sympathoexcitation and Hypertension / 神经科学通报·英文版

Angiotensin (Ang)-(1-7) is an important biologically-active peptide of the renin-angiotensin system. This study was designed to determine whether inhibition of Ang-(1-7) in the hypothalamic paraventricular nucleus (PVN) attenuates sympathetic activity and elevates blood pressure by modulating pro-inflammatory cytokines (PICs) and oxidative stress in the PVN in salt-induced hypertension. Rats were fed either a high-salt (8% NaCl) or a normal salt diet (0.3% NaCl) for 10 weeks, followed by bilateral microinjections of the Ang-(1-7) antagonist A-779 or vehicle into the PVN. We found that the mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma norepinephrine (NE) were significantly increased in salt-induced hypertensive rats. The high-salt diet also resulted in higher levels of the PICs interleukin-6, interleukin-1beta, tumor necrosis factor alpha, and monocyte chemotactic protein-1, as well as higher gp91 expression and superoxide production in the PVN. Microinjection of A-779 (3 nmol/50 nL) into the bilateral PVN of hypertensive rats not only attenuated MAP, RSNA, and NE, but also decreased the PICs and oxidative stress in the PVN. These results suggest that the increased MAP and sympathetic activity in salt-induced hypertension can be suppressed by blockade of endogenous Ang-(1-7) in the PVN, through modulation of PICs and oxidative stress.

Optimization of Paeonol NLC Thermosensitive Gel Formulation by Box-Behnken Response Surface Methodology / 中国中医药信息杂志

Objective To optimize the formulation of paeonol nanostructured lipid carrier (NLC) thermosensitive in situ gel through Box-Behnken response surface method; To investigate its release properties in vitro to provide references for the study of transdermal drug delivery system. Methods Taking mass fraction of poloxamer 407 and poloxamer 188 as the factors, the gelling temperature as the index, the mathematical relationship between the gelling temperature and two factors was established by binomial model and multivariate linear regression model. The Box-Behnken response surface method was used to optimize the formulation of paeonol NLC thermosensitive in situ gel, and the in vitro release characteristics of the preparation was investigated. Results There was a credible quantitative relationship between the gelling temperature and the 2 factors, and the binomial model was more reliable than the multivariate linear model. The best prescriptions of paeonol NLC thermosensitive in situ gel were 22.90% poloxamer 407 and 3.34% poloxamer 188; gelling temperature was (33.4±0.1)℃, and the cumulative release amount of paeonol in situ gel in 24 h was 51.19%. Conclusion This method is suitable for the formulation optimization of paeonol NLC thermosensitive in-situ gel, and the established mathematical model has good predictability. The optimized formulation can provide references for the development of paeonol transdermal preparation.

Study on Physicochemical Properties and Antioxidant Activity of Crude Polysaccharide from Alhagi Sparsi-folia Shap.Stem-branch / 中国药师

Obejctive:To study the extraction, separation, physical and chemical properties and antioxidant activity of the crude polysaccharide from Alhagi sparsifolia Shap.stem-branch.Methods: The crude polysaccharide from Alhagi sparsifolia Shap.stem-branch was extracted by ethanol subsiding method .The total sugar content was determined by phenol-sulfuric acid method and the pro-tein content was determined by coomassie brilliant blue method .The content of uronic acid was determined by carbazole sulfuric acid method and the monosaccharide composition and the relative molar ratio were determined by GC .The antioxidant activities in vitro were evaluated by determining the reducing power of polysaccharide from Alhagi sparsifolia Shap stem-branch and its removal ability to 1,1-diphenyl-2-trinitrophenylhydrazine ( DPPH) radicals and hydroxyl radicals .Results: The total sugar content of crude polysaccharide from Alhagi sparsifolia Shap.stem-branch was 73.2％, and uronic acid accounted for 27.2％of the total sugar content of crude poly-saccharide.The content of protein was 17.6％.The crude polysaccharide from Alhagi sparsifolia Shap .stem-branch was composed of Rha, Ara, Xyl, Man, Glc, Gal, GlcA and GalA, and the relative molar ratio was 1.05:1.00:1.25:0.52:3.05:1.31:0.47:4.78. The reducing power of the polysaccharide from Alhagi sparsifolia shap.stem-branch and the clearance rate on DPPH radicals and hy-droxyl radicals increased with the increase of polysaccharide concentration .Conclusion:The crude polysaccharide from Alhagi sparsi-folia Shap.stem-branch was extracted , and the physical and chemical properties and antioxidant activity in vitro were studied, which provide foundation for the further investigation and comprehensive utilization of Alhagis parsifolia Shap.stem-branch.

Effects of Chronic Salt Loading on Plasma Inflammatory Factors in Normotensive Adults / 中国循环杂志

Objectives: To observe the effects of dietary sodium intake on plasma inflammatory factors including tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (CRP) and monocyte chemoattractant protein -1 (MCP-1) in normotensive adults. Methods: Thirty normotensive volunteers, aged 18 to 60 years old, were selected to undergo baseline survey, low-sodium diet (51.3 mmol per day) for 7 days, followed by high-sodium diet (307.8 mmol per day) for 7days. Subjects were classified as salt sensitive (SS, 10 subjects) or non-salt sensitive (NSS, 20 subjects) based on their mean arterial blood pressure (MAP) increase (SS: more than 10 percent increase at the end of the high-sodium phase compared with the end of low-sodium phase). Fasting blood samples were taken on the first day of baseline and on the sixth day of the two intervention phases. Plasma TNF-α and MCP-1 concentration was measured using an enzyme-linked immunosorbent assay system, plasma hs-CRP concentration was measured by immune nephelometry. Results: The prevalence of SS is 33%. After salt loading, no significant change was found in the plasma hs-CRP concentrations; Whereas plasma TNF-α level increased significantly in both of the SS and NSS groups(pg/ml, [168.4±67.8 vs 42.1±26.7], P<0.01 and [129.8±24.1 vs 37.7±15.8], P<0.01, respectively) ; Plasma MCP-1 was also significantly higher during the high-sodium than the low-sodium phase in both SS and NSS groups(pg/ml, [205.2±64.2 vs 166.3±48.5], P<0.01and [212.3±52.2 vs 143.6±55.9], P<0.01). Conclusions: High-sodium diet can induce an inflammatory state independent of the salt sensitivity in normotensive subjects.

Modified poisoning severity score for early prognostic evaluation in acute paraquat poisoning / 解放军医学杂志

Objective To study the applied value of modified poisoning severity score (PSS) for early prognostic evaluation in acute paraquat poisoning.Methods Thirty-seven patients with acute paraquat poisoning from June 2013 to June 2016 were enrolled.The PSS score,the modified PSS score,the acute physiology and the chronic health status Ⅱ score (APACHE Ⅱ) of the patients were calculated.The relationship between modified PSS and APACHE Ⅱ was analyzed.Also the factors that affect outcome were analyzed by logistic regression analysis.The work characteristic curve (ROC curve) of the PSS,the modified PSS and the APECH Ⅱ were drawn and compared.Results There was a positive correlation between the risk of death and admission time,poisonous dose,the concentration of urine paraquat,and white blood cell count (P＜0.05).There was a significant correlation between the modified PSS and the APACHE Ⅱ (P＜0.0001).The immediate PSS score,the modified PSS score,and the APACHE Ⅱ score were significant for the prognosis of patients with acute paraquat poisoning.The area under the curve (AUC) was in turn 0.774,0.788,0.799.Among them,the best bound of the modified PSS score was 6.5 (when the score is greater than 6.5,the risk of death is higher).Further comparison of the area under the three curves showed that there was no significant difference in the area under the ROC curve between the three scores in predicting the prognosis of death [P=0.7633(PSS-DPSS),P=0.7791 (PSS-APACHE Ⅱ),P=0.8918(DPSS-APACHE Ⅱ)].Conclusion Modified PSS is helpful in early predicting the prognosis of acute paraquat poisoning.

A comparative study of two methods of intruding overerupted upper molars / 口腔疾病防治

Objective@# To compare the clinical effects of the two methods of intruding overerupted molars by microscrews.@*Methods @#21 overerupted molars were selected and ramdomly divided into group A and group B. Group A was implanted with one microscrew anchorage at the side of the buccolingual tongue, and the force was produced by the tension spring. Group B was implanted with two microscrews combined with nickel - titanium fragments to lower the molars. The distances, velocities and microscrew anchorage failure rates were measured and compared between the two groups. @*Results @#Two methods can achieve significant depressing effect, however, the failure rate of micro-screws was different in the two methods. The failure rates of group A and group B were 27.3% and 5.0%, respectively. The average speed of group A was 0.37 mm / month, and group B was 0.33 mm / month.@*Conclusion@#Both microscrew anchorage methods can effectively intrude overerupted upper molars. The speed of intrusion with microscrews directly is faster than NiTi Segmental arch and microscrews, but the implant failure of microscrews is higher.

Study on regulation mechanism of Toutongning capsule through TNF signaling pathway in treatment of migraine based on systems pharmacology method / 中国中药杂志

Toutongning capsule (TTNC) is a traditional Chinese medicine(TCM) with good effect for treating migraine in clinical application. In this paper, a systems pharmacology method was carried out to study the TNF mechanism of the TTNC on the migraine. First, the ingredients for TTNC were collected from TCM databases, and ADME properties prediction was firstly applied to screen out the active compounds of TTNC. Then, the target searching and identification was performed by using CSDT model, and the targets were mapped to the migraine disease to determine the active targets through some common databases like TTD. To obtain the targets related with TNF signaling pathway, KEGG pathway analysis was performed by DAVID online analysis tool. Finally, the "herbs-compounds-targets" network was built by Cytoscape software. According to the results of degree and betweenness in the network, the key active compounds and targets were determined to explore the TNF mechanism for TTNC. Results showed that 19 active compounds and 8 targets played a crucial role in the treatment of migraine by TNF pathway for TTNC. This work provided a new perspective to deepen the understanding of the TNF signaling pathway mechanism in migraine treatment by TTNC, and may provide a necessary theoretical basis for the determination of effective markers and the clinical research of this medicine.

Identification of 2-oxohistidine Interacting Proteins Using E. coli Proteome Chips.

Cellular proteins are constantly damaged by reactive oxygen species generated by cellular respiration. Because of its metal-chelating property, the histidine residue is easily oxidized in the presence of Cu/Fe ions and H2O2 via metal-catalyzed oxidation, usually converted to 2-oxohistidine. We hypothesized that cells may have evolved antioxidant defenses against the generation of 2-oxohistidine residues on proteins, and therefore there would be cellular proteins which specifically interact with this oxidized side chain. Using two chemically synthesized peptide probes containing 2-oxohistidine, high-throughput interactome screening was conducted using the E. coli K12 proteome microarray containing >4200 proteins. Ten interacting proteins were identified, and successfully validated using a third peptide probe, fluorescence polarization assays, as well as binding constant measurements. We discovered that 9 out of 10 identified proteins seemed to be involved in redox-related cellular functions. We also built the functional interaction network to reveal their interacting proteins. The network showed that our interacting proteins were enriched in oxido-reduction processes, ion binding, and carbon metabolism. A consensus motif was identified among these 10 bacterial interacting proteins based on bioinformatic analysis, which also appeared to be present on human S100A1 protein. Besides, we found that the consensus binding motif among our identified proteins, including bacteria and human, were located within α-helices and faced the outside of proteins. The combination of chemically engineered peptide probes with proteome microarrays proves to be an efficient discovery platform for protein interactomes of unusual post-translational modifications, and sensitive enough to detect even the insertion of a single oxygen atom in this case.

Systematic protein interactome analysis of glycosaminoglycans revealed YcbS as a novel bacterial virulence factor.

Microbial pathogens have evolved several strategies for interacting with host cell components, such as glycosaminoglycans (GAGs). Some microbial proteins involved in host-GAG binding have been described; however, a systematic study on microbial proteome-mammalian GAG interactions has not been conducted. Here, we used Escherichia coli proteome chips to probe four typical mammalian GAGs, heparin, heparan sulphate (HS), chondroitin sulphate B (CSB), and chondroitin sulphate C (CSC), and identified 185 heparin-, 62 HS-, 98 CSB-, and 101 CSC-interacting proteins. Bioinformatics analyses revealed the unique functions of heparin- and HS-specific interacting proteins in glycine, serine, and threonine metabolism. Among all the GAG-interacting proteins, three were outer membrane proteins (MbhA, YcbS, and YmgH). Invasion assays confirmed that mutant E. coli lacking ycbS could not invade the epithelial cells. Introducing plasmid carrying ycbS complemented the invading defects at ycbS lacking E. coli mutant, that can be further improved by overexpressing ycbS. Preblocking epithelial cells with YcbS reduced the percentage of E. coli invasions. Moreover, we observed that whole components of the ycb operon were crucial for invasion. The displacement assay revealed that YcbS binds to the laminin-binding site of heparin and might affect the host extracellular matrix structure by displacing heparin from laminin.

Research progress in stimuli responsive mesoporous silica nanoparticles for cancer diagnosis and therapy / 中国药学杂志

Referring to the recent literatures, this review summarized the recent research progress of SR-MSNDDS which were responsive to different stimulus, including pH, reduction, temperature, light, magnetic field or biomolecules, etc. To review the recent research progress of stimuli responsive mesoporous silica nanoparticle (SR-MSNDDS) drug delivery systems and predict their application prospect. SR-MSNDDS could overcome the problem of controlling drug release from MSN and achieve tumor specific drug release, which has become a research hotspot in the field of tumor diagnosis and therapy.