ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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．
ABSTRACT
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.
Subject(s)
Animals , Acanthaceae , Accidental Falls , Alternaria , Ascomycota , Beak , China , Classification , DNA, Ribosomal , Hevea , Rubber , Spores, FungalABSTRACT
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.
ABSTRACT
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.
Subject(s)
Animals , Male , Angiotensin I , Metabolism , Antioxidants , Pharmacology , Blood Pressure , Hypertension , Drug Therapy , Oxidative Stress , Paraventricular Hypothalamic Nucleus , Peptide Fragments , Metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species , Metabolism , Sodium Chloride, Dietary , PharmacologyABSTRACT
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.
Subject(s)
Aged , Humans , Middle Aged , Anemia, Macrocytic , Erythrocyte Indices , Myelodysplastic Syndromes , ReticulocytesABSTRACT
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.
Subject(s)
Alkaloids , Fritillaria , Chemistry , Microbiology , Mycorrhizae , Plant Roots , Rhizosphere , Soil MicrobiologyABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four cases subjected to routine MHD complicated with skin pruritus admitted to our hospital were selected and randomly divided into case group (n=28) and control group (n=26). The control group was given routine MHD alone. The case group was given lanthanum carbonate additionally on the basis of routine MHD. The changes of itching degrees at first and third month, and serum calcium, phosphorus, calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC scores at third month after treatments were compared between the two groups. The correlation between calcium-phosphorus products and AAC scores was also analyzed. There was no significant difference in the baseline of blood urea nitrogen (BUN), serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, total cholesterol between case group and control group (P>0.05 for all). There was also no significant difference in the baseline itching scores between the case group and the control group (P>0.05). At 1st and 3rd month after treatment, the itching scores in the case group were 14.2 ± 3.2 and 10.5 ± 2.3, respectively, which were significantly lower than the baseline and those in the control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching scores in the control group were 23.6 ± 5.9 and 24.8 ± 6.3, respectively, which were significantly higher than the baseline (P<0.05). There was no significant difference in the baseline of serum calcium, phosphorus, calcium-phosphorus products, iPTH levels between the case group and control group (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus products and iPTH levels in the case group were decreased significantly as compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium-phosphorus products, and iPTH levels were statistically decreased as compared with those in the control group (P<0.05). The AAC scores showed statistically significant difference between the case group and the control group (P<0.05). The serum phosphorus and AAC scores showed a positive correlation in both two groups. It was suggested that the administration of lanthanum carbonate in the elderly MHD patients can effectively relieve itching, and simultaneously reduce serum phosphorus and iPTH levels, resulting in the attenuation of vascular calcification.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Case-Control Studies , Lanthanum , Therapeutic Uses , Parathyroid Hormone , Phosphates , Blood , Pruritus , Blood , Drug Therapy , Renal Dialysis , Methods , Treatment Outcome , Vascular Calcification , Blood , Drug TherapyABSTRACT
<p><b>OBJECTIVE</b>This study was to investigate the molecular biomarkers of apoptosis induced by BH3 mimetic S1 in human primary AML cells.</p><p><b>METHODS</b>Mononuclear cells were isolated from 27 newly diagnosed AML samples. Apoptosis was analyzed by flow cytometry. IC(50) value of S1 on these samples was determined by XTT assay. The expression level of BCL-2 family members and phosphorylated BCL-2 were assessed by Western blot with subsequent semi-quantitatively densitometric analysis. XTT assay was performed to determine the cell viability of the combined use of S1 and MEK/ERK inhibitor PD98059. The interactions between BCL-2 and pro-apoptosis proteins were tested by co-immunoprecipitation.</p><p><b>RESULTS</b>The flow-cytometry detection showed that S1 induced the apoptosis of primary AML cells. Based on the responses, 27 primary samples could be classified into three groups: (1) a sensitive group (12 of 27 cases) with IC(50)<14 µmol/L, (2) an intermediate group (8 of 27 cases) with IC(50) of 14-30 µmol/L and (3) a resistant group (7 of 27 cases) with IC(50)>30 µmol/L. The ratio of pBCL-2/(BCL-2+MCL-1) showed a good linear correlation with the IC(50) values. (R(2) = 0.71, P < 0.0001). PD98059 suppressed BCL-2 phosphorylation. When PD98059 suppressed BCL-2 phosphorylation, the apoptotic rate of drug-resistant cells induced by S1 increased from 9.8% to 64.5% (combination index, CI = 0.4), accompanied by more dissociation of BCL-2 heterodimers.</p><p><b>CONCLUSION</b>The combination of S1 with PD98059 decrease pBCL-2 level of AML patients and inhibits of the anti-apoptotic function of BCL-2 through enhancing the dissociation of BCL-2 heterodimers.</p>
Subject(s)
Humans , Antimetabolites, Antineoplastic , Apoptosis , Cell Line, Tumor , Drug Combinations , Leukemia, Myeloid, Acute , Molecular Mimicry , Oxonic Acid , Phosphorylation , Proto-Oncogene Proteins c-bcl-2 , TegafurABSTRACT
Participating in the international conferences helps to get the latest progress in cer-tain areas. It provides important channels of communication and platform for cooperation. The article summarized the categories of international conferences, access to it, way to apply for it, how to apply for financial support, visa and passport, as wellas preparations before. The author's experience attend-ing the seventh Asia-Pacific conference neurochemistry(APSN) held in Singapore, may offer some help for reference.
ABSTRACT
<p><b>OBJECTIVE</b>Suppressors of cytokine signaling (SOCS) have been shown to play an important role in regulating cytokines, such as intracellular interferon (IFN) and interleukin (IL), in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. At present, the association between SOCS and asthma is still under study. The aim of this study is to explore the relationship of SOCS-1 and SOCS-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) with the intracellular IFN-'/IL-4 ratio in CD4+ T cells and specific IgE (sIgE) level in children with asthma.</p><p><b>METHODS</b>BMCs were collected from 44 children with allergic asthma (4-14 years) and 30 healthy children. The intracellular IFN-'/IL-4 ratio in CD4+ T cells was measured by flow cytometry. Total RNAs were extracted from the PBMCs and SOCS-1 and SOCS-3 mRNA expression was measured by SYBR Green I quantitative RT-PCR.</p><p><b>RESULTS</b>Compared with the healthy children, children with allergic asthma showed a lower level of intracellular IFN-' in peripheral blood [(15.7±2.0)% vs (19.1±2.7)%] and IFN-'/IL-4 ratio (3.4±1.5 vs 4.8±2.9) and higher SOCS-1 mRNA expression (-Ct, 11.1±1.9 vs 12.6±2.8). There was a negative relationship between SOCS-1 mRNA expression and the percentage of IFN-'-producing CD4+ T cells in peripheral blood in both asthmatic and healthy children (P<0.05). No correlation was found between SOCS-1 and SOCS-3 expression and sIgE level.</p><p><b>CONCLUSIONS</b>Children with allergic asthma have elevated levels of SOCS-1 mRNA in PBMCs, which is associated with Th2-skewed immune response.</p>