STIP1 correlates with tumor immune infiltration and prognosis as a potential immunotherapy target: a pan-cancer bioinformatics analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy.@*METHODS@#TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1.@*RESULTS@#Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P < 0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P < 0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P < 0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P < 0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism.@*CONCLUSION@#STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.

Association of Serine/Threonine Phosphoprotein Phosphatase 4C Expression With Prognosis of Gastric Cancer / 中国医学科学院学报

Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.

Extension and dentin differentiation potential of dental pulp stem cells from human deciduous teeth on the stiff matrix surface / 中国组织工程研究

BACKGROUND: Dental pulp stem cells can differentiate into dentin under appropriate induction conditions, which are important seed cells i n dental tissue engineering. However, the commonly used inducers are chemical agents, which are not available for in vivo application. Mesenchymal stem cells can differentiate with the material hardness, and the physical property-induced cell differentiation is little reported. OBJECTIVE: To observe the extension characteristics and dentin differentiation potential of dental pulp stem cells from human deciduous teeth on the stiff matrix surface. METHODS: Dental pulp stem cells from naturally shed deciduous teeth were isolated, cultured and identified. Four solid gel matrixes with elasticity modulus of (9.12±0.94), (27.18±3.55), (59.37±4.05) and (86.45±5.33) kPa were made using low melting point agarose. The extension ability of passage 4 dental pulp stem cells on the surface of the above solid matrixes was detected by two-dimensional clone formation and cell scratch tests. The protein expression levels of dentin matrix protein-1, dentin phosphoprotein and dentin sialoprotein were detected by western blot assay. RESULTS AND CONCLUSION: Dental pulp stem cells from human deciduous teeth seeded on the gel matrix with extremely low and low hardness almost existed as cell clones with neat edges, and cell spreading and extension were rare. When seeded on the gel matrix with moderate and high hardness, the cloned edge of deciduous dental pulp stem cells spread and extended obviously. The cell body became large and the cell edge extended significantly. The cell scratch test revealed the similar phenomenon. When seeded on the gel matrix with moderate and high hardness, dental pulp stem cells from human deciduous teeth exhibited high expression levels of of dentin matrix protein-1, dentin phosphoprotein and dentin sialoprotein. In summary, with the increase of matrix hardness, the abilities of extension and differentiation into dentin of dental pulp stem cells from human deciduous teeth are increased gradually, which provides a method for dental tissue engineering.

TP53 pathogenic variants related to cancer / Variantes patogénicas de TP53 relacionadas con cáncer

TP53 or P53 is a tumor suppressor gene known as the "genome guardian", responsible for inducing cell response to DNA damage, by stopping the cell cycle in case of mutation, activating DNA repair enzymes, initiating senescence and activation of apoptosis. Mutations in the gene sequence can cause non-synonymous mutations or errors in the reading frame by insertion, deletion or displacement of nucleotides: e.g., c.358A>G mutation in exon 4 and variants located in exons 9 and 10 of the TD domain. Therefore, in this review, we will see that changes in the reading frame, including the loss of one or two base pairs could prevent accurate transcription or changes in the structure and function of the protein, and could completely impair reparation function. These changes promote self-sufficiency in growth signaling, insensitivity to anti-growth signals, and evasion of apoptosis, resulting in limitless replication and induction of metastatic angiogenesis, generating as a consequence the proliferation of tumor, neoplastic, and lymphoid cells. Taking into account the importance of TP53 in the regulation of the cell cycle, the objective of this review is to update information related to the role of this gene in the development of cancer and the description of genetic variations.

TP53 o P53 es un gen supresor de tumores conocido como el "guardián del genoma", encargado de inducir la respuesta de la célula ante el daño del ADN, deteniendo el ciclo celular en caso de mutación, activando enzimas de reparación del ADN, iniciando el proceso de senescencia celular y activación de la apoptosis. Las mutaciones en la secuencia del gen pueden originar mutaciones no sinónimas o errores en el marco de lectura por la inserción, deleción o desplazamiento de nucleótidos: ejemplo, mutación c.358A>G en el exón 4 y variantes que se albergan en los exones 9 y 10 del dominio TD. Por lo tanto en esta revisión examinaremos cambios en el marco de lectura, incluyendo la pérdida de una o dos pares de bases, que podrían impedir la exacta transcripción o cambiar la estructura y función de la proteína o perjudicar completamente la función de reparación. Tales cambios promueven la auto-suficiencia en la señal de crecimiento, la insensibilidad a señales anticrecimiento y la evasión de la apoptosis, lo que resulta en la replicación ilimitada y la inducción de angiogénesis metastásica, generando como consecuencia la proliferación de células tumorales, neoplásicas y linfoides. Teniendo en cuenta la importancia del TP53 en la regulación del ciclo celular, el objetivo de la presente revisión es actualizar la información relacionada con el papel de este gen en el desarrollo de cáncer y la descripción de las variaciones genéticas.

Measles virus phosphoprotein inhibits apoptosis and enhances clonogenic and migratory properties in HeLa cells

Measles virus is the causative agent of measles, a major cause of child mortality in developing countries. Two majorproteins, coded by the viral genome, are nucleocapsid protein (N) and phosphoprotein (P). The N protein protects the viralgenomic RNA and forms ribonucleoprotein complex (RNP) together with P protein. MeV-P protein recruits the largeprotein (L), i.e. viral RNA-depended RNA polymerase (RdRp), to ensure viral replication in host cell. Apoptogenicproperties of N protein of Edmonston vaccine strain have been established in our lab previously. We investigated the role ofMeV-P protein of Edmonston vaccine strain as modulator of apoptosis in cervical cancer cell line (HeLa) and found thatMeV-P protein is anti-apoptotic and enhances cell proliferation. Measles virus is considered to be innately oncotropic virus.However, the anti-apoptotic property of MeV-P protein raises important concerns while adopting this virus as an anti-cancertherapeutic tool.

miR-9 inhibits the proliferation and migration of esophageal cancer EC109 cells by regulating GOLPH3 / 临床检验杂志

Objective@#To investigate the expression level of miR-9 in esophageal cancer and its effect on the biological function of esophageal cancer cells. @*Methods@#The expression levels of miR-9 and Golgi phosphoprotein 3 (GOLPH3) in esophageal cancer and its adjacent tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). The miR-9 mimics was transfected into esophageal cancer EC109 cells, and the expression level of miR-9 was detected by qRT-PCR. The effects of overexpression of miR-9 on the biological function of EC109 cells were determined by the MTT assay, plate colony formation assay, Transwell migration assay and flow cytometry. The wild and mutant GOLPH3 double luciferase reporter gene vectors were constructed, and luciferase activity was detected. The effects of overexpression of miR-9 on the expression levels of GOLPH3 mRNA and protein were detected by qRT-PCR and Western blot. @*Results@#Compared with the adjacent tissues, the expression level of miR-9 in esophageal cancer tissues decreased significantly (P＜0.01), while that of GOLPH3 increased significantly (P＜0.01). Compared with the negative control group, the expression level of miR-9 in EC109 cells transfected with miR-9 mimics increased significantly (P＜0.01), and the proliferation and migration ability of the EC109 cells decreased obviously (P＜0.01). The cell cycle of the EC109 cells was blocked in G2/M phase (P＜0.01). The dual luciferase reporter assay, qRT-PCR and Western blot confirmed that miR-9 could bind with GOLPH3 specifically (P＜0.01), and mediate the degradation of GOLPH3 mRNA (P＜0.01), which led to the decrease of GOLPH3 protein expression level (P＜0.05). @*Conclusion@#MiR-9 is low expression in esophageal cancer, and may participate in the occurrence and development of esophageal cancer by regulating GOLPH3.

Expression and clinical significance of proline-rich tyrosine kinase 2 and phospho-protein kinase B in tongue squamous cell carcinoma / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the expression and clinical significance of proline-rich tyrosine kinase 2 (Pyk2) and phospho-protein kinase B (p-AKT) in tongue squamous cell carcinoma (TSCC) and adjacent nontumor tissues.@*METHODS@#The Pyk2 and p-AKT protein levels were detected via immunohistochemistry in 45 cases of TSCC tissues and 30 cases of adjacent nontumor tissues. The relationships of the two protein levels and clinicopathological characteristics were also analyzed.@*RESULTS@#Pyk2 and p-AKT levels were significantly higher in the TSCC tissues than in the adjacent nontumor tissues (P<0.05). Nontumor tissues showed poor or no expression. The expression levels of the two proteins were positively correlated (γs=0.412). The expression of Pyk2 was associated with histopathological differentiation type, regional lymph node metastasis, and TNM staging (P<0.05), but not with age and gender. The expression of p-AKT was only related to histopathological differentiation types (P<0.05).@*CONCLUSIONS@#The abnormal expression of Pyk2 and p-AKT proteins might be closely related to the development and progression of TSCC. Joint detection can be used as an indicator to estimate the degree of TSCC.

Role of NO/VASP Signaling Pathway against Obesity-Related Inflammation and Insulin Resistance

Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.

pp65 antigen and human cytomegalovirus infection / 国际儿科学杂志

HCMV infection can cause hepatopathy,pneumonia,diarrhea,thrombocytopenic purpura,and sensorineural hearing loss(SNHL),with high morbility and mortality.pp65(phosphoprotein 65),a major constitutive protein of virion,is closely associated with viral gene expression,immune evasion and cell metabolism.pp65 antigenemia level has positive correlation with clinical symptom,which can guide the preemptive therapyand improve prognosis,is considered as one of the golden standard methods of active cytomegalovirus infection.In this paper,the pp65 protein properties,pathogenesis,application in diagnosis and prevention are reviewed.

Antiplatelet aggregation of naringenin via cyclic nucleotide signaling: in vitro studies / 中国病理生理杂志

AIM: To investigate effect of naringenin on ADP-induced platelet aggregation and its possible mechanism.METHODS: The levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in the platelets with ADP stimulation using ELISA in the presence or absence of different concentrations of naringenin.The effect of naringenin at different concentrations on the change of phosphodiesterase (PDE) activity was measured by high efficiency liquid chromatography.The effects of naringenin at different concentrations on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at positions Ser157 and Ser239 in washed platelets with ADP stimulation were analyzed by Western blot.The phosphorylation of VASP at Ser239 was also analyzed in the presence of protein kinase A (PKA), protein kinase G (PKG), or protein kinase C (PKC) inhibitors before incubation with naringenin.The platelet aggregation was measured in the presence of PKA or PKG inhibitors before incubation with naringenin.RESULTS: Naringenin elevated cGMP levels significantly but not cAMP levels in the platelets with ADP stimulation in a dose-dependent manner.Naringenin inhibited PDE activity.Naringenin increased the phosphorylation of VASP at Ser239 in a dose-dependent manner in the platelets with ADP stimulation but only modest changes in the phosphorylation at position Ser157.The phosphorylation level of VASP at Ser239 position was inhibited when the platelets were treated with PKA inhibitor before incubation with naringenin.Incubation of platelets with neither PKG nor PKC inhibitors before treatment with naringenin affect the phosphorylation of VASP at Ser239.Pretreatment with PKA inhibitor but not PKG inhibitor significantly reversed the antiplatelet aggregation by naringenin in ADP-stimulated platelets.CONCLUSION: Naringenin may inhibit platelet activation through the elevation of cGMP-and PKA-mediated VASP phosphorylation.

Expression of Golgi Phosphoprotein 3 in Human Hepatocellular Carcinoma and Its Clinicopathological Significance / 中国医科大学学报

Objective To investigate the expression characteristics of Golgi phosphoprotein 3(GOLPH3)in human hepatocellular carcinoma (HCC)and explore its clinicopathological significance. Methods The expressions of GOLPH3 protein was detected in 132 cases of paired paraf-fin embedded HCC specimens and pericarcinoma tissues using immunohistochemical staining ,and the relation of the expression of GOLPH3 to clinicopathologic features was analyzed. Meanwhile,the expression and distribution of GOLPH3 in HCC cells was observed by laser confocal mi-croscopy. Results The positive expression rates of GOLPH3 in HCC and pericarcinoma tissues were 70.0%(92/132)and 42.4%(56/132) (P<0.001),respectively. The incidence of portal vein tumor thrombus in high and low GOLPH3 expression groups of HCC were 21.2%(14/66) and 6.1%(4/66)(P<0.05),respectively. The expression rate of GOLPH3 in HCC was significantly higher than that in pericarcinoma tissues, and the expression of GOLPH3 in HCC was positively related to portal vein tumor thrombus. In addition ,GOLPH3 was mainly expressed in cyto-plasm of HCC cells,and there was also scattered distribution in the nucleus. Conclusion GOLPH3 acts as an oncogene and may play vital roles in the carcinogenesis and development of HCC.

Expression and role of Golgi phosphoprotein 3 in cancer / 国际肿瘤学杂志

Golgi phosphoprotein 3 (GOLPH3 )is closely related to the development and prognosis of cancer,such as non-small cell lung cancer,breast cancer,gastric cancer,esophageal cancer,colorectal cancer,etc.The mainly tumor pathogenisis related GOLPH3 includes modulating the response to DNA damage, vesicle trafficking,mTOR signaling pathway,mitochondrial functions,cytokinesis and Golgi vesicular malignant secretion,and then promoting cell proliferation,invasion and metastasis.GOLPH3 is expected to be a new tar-get for cancer therapy,which may become an important biomarker for the diagnosis,treatment and prognosis of cancer.

Research the relationship between vasodilator-stimulated-phosphoprotein and risk factors for atherosclero-sis / 医学研究生学报

In the past few decades, accumulated experimental and clinical evidences suggest that cyclic guanosine monophos-phate (cGMP) plays an important role in atheroselerosis. Vasodilator-stimulated phosphoprotein (VASP), a major downstream compo-nent of the cGMP signaling cascade, is an actin-binding protein which regulates cell adhesion, morphology change, cell motility and cell proliferation. It has shown that VASP is associated with many factors influencing atherosclerosis, and it plays an important role in the genesis and development of atherosclerosis. The relationships between the occurrence of atherosclerosis and risk factors for athero-sclerosis such as hypertension, hyperglycaemia and hyperlipidemia are reviewed in this article.

Role of vasodilator stimulated phosphoprotein in resistin-induced proliferation and migration of human coronary endothelial cells / 医学研究生学报

Objective Resistin,also known as an adipose tissue-specific secretory factor,is involved in the development and progression of artherosclerosis by inducing dysfunction of endothelial cells,but its action mechanism has been rarely studied.The purpose of this study was to investigate the effect of resistin on the function of human coronary artery endothelial cells (HCAECs) and the underlying mechanisms.Methods We constructed the lentiviral vasodilator-stimulated phosphoprotein (VASP) shRNA interfering sequence (the LV-siVASP group) and a negative control vector (the LV-sicntr group),transfected HCAECs with VASP siRNA or control siRNA,and determined the VASP mRNA and protein expressions by quantitative RT-PCR and Western blot,respectively.We treated the HCAECs with resistin at the concentrations of 0,10,50,100,and 200 ng/mL followed by-detection of its effects on the proliferation and migration of the cells by MTT and Transwell chamber assay,respectively.We made comparisons between the LV-siVASP and LV-sicntr groups in the proliferation and migration of the HCAECs treated with 100 ng/mL resistin,the expression of vascular endothelial growth factor receptor-2 (VEGFR2) by immunofluorescent staining,and the activity of RhoA by pull-down assays.Results Compared with the LV-sicntr group,the LV-siVASP group showed significantly inhibited expressions of RNA (100％ vs [68.1±0.8]％,P＜0.05) and the VASP protein (100％ vs [59.3± 1.7] ％,P＜0.05) Treatment with resistin at 50-200 ng/mL markedly increased the proliferation of the HCAECs at 48 hours (P＜0.05) and induced a dose-dependent promotion of their migration at 24 hours (P＜0.05).No significant difference was observed in the expression VEGFR2 between the two groups,while the activity if RhoA was remarkably reduced in the LV-siVASP group ([41.3±3.1] ％) as compared with the LV-sicntr group (P＜0.05).Conclusion Resistin promotes the proliferation and migration of HCAECs,and the influence of VASP ablation on the action of resistin is associated with the decreased activity of RhoA.

Expression of vasodilator-stimulated phosphoprotein relates to prostate cancer metastasis / 中华男科学杂志

<p><b>Objective</b>To investigate the relationship of the expression of vasodilator-stimulated phosphoprotein (VASP) with the metastasis and prognosis of prostate cancer.</p><p><b>METHODS</b>Prostate cancer PC3 cells were infected with VASP shRNA and control shRNA lentiviruses, respectively. The invasive ability of the PC3 cells was determined by transwell migration assay, the expression of VASP in the prostate cancer tissue from 56 patients was detected by immunohistochemistry, and the survival rate of the patients was analyzed according to the VASP expression levels and follow-up data after radical prostatectomy.</p><p><b>RESULTS</b>VASP shRNA lentivirus significantly inhibited the expression of VASP and decreased the invasive ability of the PC3 cells as compared with the results obtained in the scramble shRNA and blank control groups (P<0.05). The survival analysis of the 56 prostate cancer patients showed that the time of biochemical recurrence was markedly shorter in the VASP positive and strongly positive groups than in the VASP-negative cases (P<0.05), but with no statistically significant difference between the former two groups (P>0.05).</p><p><b>CONCLUSIONS</b>VASP is involved in the regulation of the invasive ability of prostate cancer PC3 cells, and the differences in the VASP expression are related to the prognosis of prostate cancer.</p>

Four detection methods for antiplatelet function of clopidogrel: A comparative study / 第二军医大学学报

Objective To assess the consistencies of VerifyNow system, thrombelastography (TEG), vasodilator-stimulated phosphoprotein (VASP), and PL-11 platelet analyzer in detecting the antiplatelet function of clopidogrel, and to discuss the clinical application values. Methods Totally 98 consecutive inpatients with ST-segment elevation myocardial infarction (STEMI), non-(NSTEMI), or coronary artery in-stent restenosis (SR) were included in this study. The patients were given a loading dose of 600-mg clopidogrel for 6 hours, 300-mg clopidogrel for at 24 hours, or chronic clopidogrel therapy (75 mg daily for ≥ 7 days) before the procedure. And then the antiplatelet effects were evaluated by VerifyNow, TEG, VASP and PL-11 platelet analyzer simultaneously, with the results of VerifyNow taken as the gold standard and P2Y12 reaction unit (PRU) ≥ 208 taken as high on-clopidogel treatment platelet reactivity (HTPR). Correlation analysis was done for the four methods, and area under ROC curve (AUC) was used to evaluate the value of each method for HTPR. Results The platelet inhibition rate detected by VerifyNow was positively correlated with that by TEG (r = 0. 234, P < 0. 05); by contrast, it was negatively correlated with the platelet reactivity index (PRI) measured by VASP, the maximum platelet aggregation rate (MAR) by PL-11 and the maximum adenosine diphosphate (MA-ADP) by TEG (r = –0. 299, P<0. 01; r = –0. 330, P< 0.05; r = –0. 237, P<0. 05). The PRU values was negatively correlated with the platelet inhibition rate detected by VerifyNow (r = –0.815, P < 0. 01). The area under ROC curve of PL-11 platelet analyzer was the highest (0. 644). Conclusion TEG, VASP, and PL-11 platelet function testing systems all have consistency with the “gold standard” VerifyNow in some extent, with PL-11 platelet analyzer showing the highest sensitivity and specificity.

Research on effect of clopidogrel on platelet VASP phosphorylation level after PCI operation / 国际检验医学杂志

Objective To use the flow cytometry to detect the platelet vasodilator-stimulated phosphoprotein(VASP)phospho-rylation level and to evaluate the clopidogrel curative effect after PCI.Methods 17 cases in the control group without any drug in-tervention and 26 cases of acute coronary syndrome(ACS)after PCI operation with clopidogrel were selected.Platelet VASP phos-phorylation levels at being selecting and on 7 d after anti-platelet therapy were detected by the flow cytometry and the platelet reac-tivity index (PRI)was calculated.Results The PRI after anti-platelet therapy in the ACS group was decreased significantly,the difference between before treatment and after treatment had statistical significance (P <0.05 ).Conclusion The platelet VASP phosphorylation level detected by the flow cytometry can specifically evaluate the effect of clopidogrel.

Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon alpha Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection

BACKGROUND/AIMS: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon alpha (PEG-IFN-alpha)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. METHODS: Two SNPs in the promoter region of SPP1 at the -443 C>T and -1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. RESULTS: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the -443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs 50.98%, pT and -1748 G>A loci may be useful markers for predicting the response to PEG-IFN-alpha-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection.

Identification of human cytomegalovirus phosphoprotein 65 in C57BL/6 and BXSB mice as a potential trigger of systemic lupus erythematosus related serum markers

Objective: To investigate the potential role of human cytomegalovirus lower matrix phosphoprotein 65 (HCMV-pp65) in murine systemic lupus erythematosus (SLE). Methods: The prokaryotic plasmid pET-28b-pp65 was constructed to express the HCMVpp65 protein. BXSB mice and C57BL/6 mice were inoculated with pp65 eukaryotic plasmid pcDNA3.0-pp65 intramuscularly 5 times at 2-week intervals, and then the blood of the mice was subsequently collected via the retro-orbital vein. Indirect ELISAs were used to evaluate the concentration of anti-pp65 immunoglobulin G, anti-double-stranded DNA and antinuclear antibodies. Interleukin-1β and tumor necrosis factor-α were also determined by competitive ELISA. At the same time, 3 major SLE-related circulating microRNAs were examined by quantitative RT-PCR. Results: The early production of autoantibodies was observed in pp65-immunized male BXSB as well as C57BL/6 mice. Overexpression of interleukin-1β and tumor necrosis factor-α were detected in pp65-immunized male BXSB mice. Quantitative RT-PCR analyses showed that three SLE related microRNAs (microRNA-126, microRNA-125a, and microRNA-146a) were downregulated in peripheral blood mononuclear cells of pp65-immunized mice. Conclusions: Our findings indicate that HCMV-pp65 immunization strongly triggers the development and progression of SLE-like disease in both BXSB and C57BL/6 mice, which indicates that the immune responses induced by HCMV-pp65 may be involved in the development of SLE.

Impact on the dopaminergic neurons of olfactory bulb in cynomolgus monkeys damaged by MPTP / 解剖学报

Objective To explore the localization and expression of dopaminergic neurons in olfactory bulb of cynomolgus monkeys damaged by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).Methods Three adult cynomolgus monkeys were injected with MPTP to induce the damage of dopamine neurons ( MPTP group ) and three adult cynomolgus monkeys were as a control group .Immunohistochemical staining was performed to examine the localization and expression of dopaminergic neurons in the olfactory bulb in normal and MPTP group monkeys .The numbers of DA-positive and DARPP32-positive cells were counted and the average absorbance was measured in normal and MPTP group .Results DA and DARPP32 positive neurons were concentrated in the glomerular layer ( GL) of olfactory bulb.DA positive nerve fibers were distributed in the GL while DARPP 32 positive nerve fibers appeared in all layers , and most nerve fibers were in GL and external plexiform layers (EPL).After MPTP injury, compared with the normal control group , DA and DARPP32 positive neurons and nerve fibers decreased in MPTP group and DA neurons and nerve fibers decreased significantly . Conclusions DA neurons and nerve fibers are in the GL of cynomolgus monkey olfactory bulb .DA neurons and fibers are significantly reduced in the olfactory bulb of cynomolgus monkeys damaged by MPTP , which may be associated with the dysosmia in Parkinson ’ s disease .