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Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.
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Resumo Fundamento A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. Objetivos Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. Métodos Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados Pacientes com DAC exibiram níveis significativamente mais baixos de sOSMR e sgp130 e níveis mais altos de OSM em comparação ao grupo de controle (ambos p <0,0001). A análise clínica mostrou níveis mais baixos de sOSMR em homens ([OR] = 2,05, p = 0,026), jovens (OR = 1,68, p = 0,0272), hipertensos (OR = 2,19, p = 0,041), fumantes (OR = 2,19, p = 0,017), pacientes que não apresentavam dislipidemia (OR = 2,32, p = 0,013), pacientes com infarto agudo do miocárdio [IAM] (OR = 3,01, p = 0,001) e pacientes não tratados com estatina (OR = 1,95, p = 0,031), antiplaquetário (OR = 2,46, p = 0,005), inibidores dos canais de cálcio (OR = 3,15, p = 0,028) e antidiabéticos (OR = 2,97, p = 0,005). Os níveis de sOSMR também foram correlacionados a sexo, idade, hipertensão e uso de medicamentos na análise multivariada. Conclusões Nossos dados sugerem que o aumento dos níveis séricos de OSM e a diminuição dos níveis de sOSMR e sGP130 em pacientes com injúria cardíaca podem desempenhar um papel importante no mecanismo fisiopatológico da doença. Além disso, níveis mais baixos de sOSMR foram associados a sexo, idade, hipertensão e uso de medicamentos.
Abstract Background Oncostatin M (OSM) is a pleiotropic cytokine which, after arterial injury, has proven to be to be rapidly expressed. Objectives To correlate the serum levels of OSM, soluble OSM receptor (sOSMR), and soluble fraction of glycoprotein 130 (sgp130) in patients with coronary artery disease (CAD) with clinical parameters. Methods Levels of sOSMR and sgp130 were evaluated by ELISA and OSM by Western Blot, in patients with CCS (n=100), patients with ACS (n=70), and 64 control volunteers without clinical manifestations of the disease. P-values < 0.05 were considered to be statistically significant. Results CAD patients exhibited significantly lower levels of sOSMR and sgp130 and higher levels of OSM when compared to the controls (both p < 0.0001). Clinical analysis displayed, lower levels of sOSMR in men ([OR] = 2.05, p = 0.026), youth (OR = 1.68, p = 0.0272), hypertensives (OR = 2.19, p = 0.041), smokers (OR = 2.19, p = 0.017), patients that did not present dyslipidemia (OR = 2.32, p = 0.013), patients with Acute Myocardial Infarction [AMI] (OR = 3.01, p = 0.001) and patients not treated with statin (OR = 1.95, p = 0.031), antiplatelet agent (OR = 2.46, p = 0.005), inhibitors of calcium channels (OR = 3.15, p = 0.028), and antidiabetic drugs (OR = 2.97, p = 0.005). The levels of sOSMR were also correlated with gender, age, hypertension, and use of medications in multivariate analysis. Conclusions Our data suggest that the enhanced serum levels of OSM, and decreased levels of sOSMR and sGP130 in patients with cardiac injury may play an important role in the pathophysiological mechanism of the disease. Furthermore, lower levels of sOSMR were associated with gender, age, hypertension, and the use of medications.
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The production of protein therapeutics in plants it is great potential for increasing, improving and developing the number of therapeutic protein production, therapeutic protein help for the prevention of diseases and treatments in animals and human transgenic plants are the most promising system for the production of a human therapeutic protein. The glycoproteins produced from plants are not the same as a native therapeutic proteins produced in mammals. But using the plants has more advantages such as the low cost and the large scale production is safe. Therefore biological active plant protein has become an alternative option to animal cells for the production of the therapeutic protein.
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Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019, among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results (1 patient did not undergo liver biopsy due to contraindication). Clinical, laboratory, imaging, and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3. Results Among the 8 patients with PFIC3, there were 5 male patients and 3 female patients, with a median age of 29.5 years. Of all 8 patients, 4 (50%) manifested as chronic cholestasis and 4 (50%) manifested as biliary cirrhosis, among whom 3 (75%) had the manifestation of portal hypertension. As for biochemical examination, 75% (6/8) had an increase in alkaline phosphatase, and 100% (8/8) had an increase in gamma-glutamyl transpeptidase. As for imaging examination, 50% (4/8) had cholecystitis, 25% (2/8) had gallstones, 25% (2/8) had bile duct dilatation, 75% (6/8) had splenomegaly, and 25% (2/8) had liver cirrhosis. As for liver biopsy, all 7 patients manifested as bile duct injury and/or reduction, and 57.1% (5/7) had absence of the bile duct. Multidrug resistance P-glycoprotein 3 (MDR3) immunohistochemical staining showed normal expression in 42.9% (3/7) of the patients and reduced expression in 57.1% (4/7) of the patients. Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry. Among the 7 patients with low phospholipid-associated cholelithiasis, 71.4% (5/7) had normal bile duct, 14.3% (1/7) had bile duct reduction, and 14.3% (1/7) had absence of the bile duct; among the 6 patients with intrahepatic cholestasis of pregnancy, 16.7% (1/6) had normal bile duct, 50% (3/6) had bile duct reduction, and 33.3% (2/6) had absence of the bile duct; among the 8 patients with PFIC3, 25% (2/8) had bile duct reduction and 75% (6/8) had absence of bile duct; among the 21 patients with PFIC3, 9.5% (2/21) had normal expression of MDR3, 23.8% (5/21) had a reduction in the expression of MDR3, and 66.7% (14/21) had absence of the expression of MDR3. Conclusion PFIC3 mainly manifests as cholestasis, cholelithiasis, and hepatic fibrosis. Pathological manifestation includes bile duct injury and bile duct reduction or absence of the bile duct in severe cases, and the degree of injury is associated with disease severity. MDR3 immunohistochemistry may show normal expression, reduced expression, or absence of expression, and diagnosis cannot be excluded in patients with normal expression. Genetic testing can be performed for diagnosis when necessary.
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Primary liver cancer is the fourth most common malignant tumor and the second leading cause of tumor death in China. The development of novel biomarkers for early diagnosis and treatment of liver cancer patients is important to improve the survival rate. The most common tumor biomarkers in clinical practice are glycoproteins currently. With omics technologies, the clinically significant glycoproteomics and glycomics for liver cancer diagnosis are discovered. In this article, a variety of glycobiomarkers were summarized. Methods, problems and challenges for clinical detection are posed. The relevant techniques of glycoprotein research, including high-throughput omics method and single glycoprotein detection are discussed, as well as potential liver cancer glycoprotein markers based on these techniques. The potential application of the glycoproteins in the clinical diagnosis of liver cancer is also considered.
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Platelet surface is rich in glycocalyx. It has been found that platelet glycosylation plays an important role in the physiological hemostasis mechanism, regulating the interaction between platelets and receptor proteins, and dynamically reshaping the surface glycosylation through its own glucose metabolism system. Platelet glycosylation also participates in platelet aging and clearance, and regulates platelet counts. Meanwhile, abnormal platelet glycosylation is closely related to primary immune thrombocytopenia, coronary heart disease and other related diseases, being a potential therapeutic target.
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Glycosylation is one of the most important posttranslational modification (PTM) for proteins. Glycans of glycoproteins play pivotal effects in cell recognition, signal transduction, differentiation, proliferation and immigration. The sialylation, fucosylation and degree of branching are intimately related to the development and progression of various malignancies and autoimmune diseases. Both glycans as well as glycoprotein have become the hot targets for disease biomarker exploration and therapeutic interventions.
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Objective:To correlate anti-cardiolipin antibody (aCL) and anti-β2 glycoprotein I antibody (aβ2GPI) with ischemic stroke (IS) in patients with systemic autoimmune diseases (SADs).Methods:A total of 104 patients with SADs who received treatment in the Affiliated Hospital of North Sichuan Medical College during January to December 2019 were included in this study. They were divided into two groups whether they had IS (IS group, n = 42) or not (non-IS group, n = 62). aPL positive rate was qualitatively compared between the IS and non-IS groups. aCL and aβ2GPI expression levels were quantitatively compared between the IS and non-IS groups. Logistic regression analysis was performed to evaluate the risk factors for IS in patients with SADs. Results:aPL positive rate in the IS group was significantly higher than that in the non-IS group [61.9% (26/42) vs. 40.3% (25 /62), χ2 = 4.66, P = 0.031]. The aCL-IgM and aβ2GPI-IgM levels in the IS group were (22.82 ± 27.27) RU/mL and (18.70 ± 23.95) RU/mL, respectively, which were significantly higher than those in the non-IS group [(13.34 ± 8.43) RU/mL, (7.61± 5.80) RU/mL, t = -2.18, -2.76, P = 0.034, 0.009]. Logistic regression analysis showed that aPL is an independent risk factor for IS ( P = 0.037). Conclusion:aCL and aβ2GPI are closely related to the occurrence of IS and are the independent risk factors for IS in patients with SADs.
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Abstract Introduction: Sticky platelet syndrome (SPS) is a prothrombotic condition characterized by increased platelet aggregation that causes arterial and venous thrombosis. Its diagnosis is reached by identifying increased aggregation using low concentrations of adenosine diphosphate and epinephrine in platelet aggregation tests. Objectives: To identify common mutations through exome sequencing in two patients from the same family diagnosed with SPS and, thus, contribute to the molecular study of this disease. Materials and methods: Descriptive study. In January 2018, exome sequencing was performed in a 10-year-old patient treated at Fundación HOMI (Bogotá D.C., Colombia), index case, and in one of his adult first-degree relatives, both with a history of thrombotic disease and diagnosed with SPS. Exome sequencing was performed at the Complexo Hospitalario Universitario de Santiago de Compostela (Spain) using the SureSelect Clinical Research Exome V2 software by Agilent. Results: Exome sequencing led to detect genetic variants in both cases when compared with the reference sequence. The following variant was identified in the two samples: a cytosine to thymine transition at position c.236 (NM_000174.4) of the glycoprotein (GP)Ib-IX-V complex platelet membrane receptor, which causes a heterozygous transition of the amino acid threonine to isoleucine (i.e., a transition from hydrophilic amino acid to a hydrophobic amino acid) at position p. 79 of the extracellular leucine-rich repeat domain of GPIba subunit of the (GP)Ib-IX complex, involving a conformational change of the main receptor of ligands IB alpha, which might result in platelet hyperaggregation and thrombosis. This variant has not been described in patients with SPS to date. Conclusion: The mutation identified in both samples could be related to SPS considering the importance of glycoprotein IX in platelet function.
Resumen Introducción. El síndrome de plaqueta pegajosa (SPP) es una condición protrombótica caracterizada por un incremento de la agregabilidad plaquetaria que causa trombosis arterial y venosa. Su diagnóstico se realiza al identificar el aumento de la agregabilidad utilizando bajas concentraciones de adenosín difosfato y epinefrina en pruebas de agregación plaquetaria. Objetivos. Identificar mutaciones comunes mediante secuenciación del exoma en dos pacientes de una misma familia con diagnóstico de SPP y, de esta forma, contribuir al estudio molecular de esta enfermedad. Materiales y métodos. Estudio descriptivo en el que se realizó secuenciación del exoma en un paciente de 10 años atendido en la Fundación HOMI (Bogotá, Colombia), caso índice, y en uno de sus familiares adultos en primer grado, ambos con antecedente de enfermedad trombótica y diagnosticados con SPP. La secuenciación del exoma se realizó en el Complexo Hospitalario Universitario de Santiago de Compostela (España) con el programa SureSelect Clinical Research Exome V2 de Agilent. Resultados. En la secuenciación del exoma se detectaron variantes genéticas en ambos casos en comparación con la secuencia de referencia. En las muestras de ambos pacientes se identificó una variante heterocigota consistente en una transición de citosina a timina en la posición c.236 (NM_000174.4) que provoca el cambio del aminoácido treonina por isoleucina en la posición p.79 del dominio extracelular repetitivo rico en leucina (subunidad GPIba del complejo de la glicoproteína Ib-IX-V) y que podría provocar el cambio conformacional del receptor principal del ligando Ib alfa, así como hiperagregación plaquetaria y trombosis. Esta variante no ha sido descrita previamente en pacientes con SPP. Conclusión. La mutación identificada en las muestras estudiadas podría estar relacionada con el SPP considerando la importancia de la glicoproteína IX en las funciones plaquetarias.
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Objective:To analyze the relationship of serum cartilage glycoprotein 39(YKL-40)and angiopoietin-like protein 3(ANGPTL3)with left ventricular dysfunction in elderly coronary heart disease(CHD)patients with heart failure(HF).Methods:The 84 elderly patients divided into group of CHD with HF, and 80 patients divided into group of CHD without HF treated in Shekou People's Hospital of Nanshan District, Shenzhen City from January 2018 to December 2019 were enrolled in this study.Evaluation of the left ventricular function meets the cardiac function classification standard of(NYHA). Serum YKL-40 and ANGPTL3 levels in all patients were detected.The relationships of serum YKL-40 and ANGPTL3 levels with the left ventricular dysfunction were analyzed in the two groups.Results:Serum levels of YKL-40 and ANGPTL3 were higher in the group of CHD with HF than in the group of CHD without HF[(81.24±6.32)μg/L vs.(69.33±5.89)μg/L, and(42.40±5.03)μg/L vs.(30.25±4.23)μg/L, t=12.469 and 16.700, both P<0.001]. Of 84 patients of CHD with HF assessed by NYHA heart function, 35 cases were in the mild group and 49 cases were in the severe group.Logistic regression analysis showed that the elevated serum level of serum YKL-40 and ANGPTL3 was positively correlated with the severity of left ventricular dysfunction in patients of CHD with heart failure( OR=1.548 and 1.854, P=0.002 and 0.001). The receiver operator characteristic(ROC)curve showed that the area under the ROC curve(AUC)of YKL-40, ANGPTL3 alone and the combined index in predicting left ventricular dysfunction in CHD with heart failure were >0.80, and the best predictive value could be obtained when the cut-off values of YKL-40 and ANGPTL3 were 79.535 μg/L and 40.805 μg/L, respectively. Conclusions:The elevated serum level of YKL-40 and ANGPTL3 may indicate the more severe left ventricular dysfunction in patients of CHD with heart failure.Early monitoring of serumYKL-40 and ANGPTL3 levels has an important clinical significance in guiding early prediction and intervention of left ventricular dysfunction in patients of CHD with heart failure.
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Objective:To investigate the predictive value of serum C-type lectin-like receptor 2 (CLEC-2) combined with insulin resistance in the outcome of patients with acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with AIS received alteplase intravenous thrombolytic therapy in the Department of Neurology, the Second Affiliated Hospital of Nantong University from October 2019 to March 2021 were enrolled retrospectively. According to the modified Rankin Scale score at 90 d after onset, they were divided into good outcome group (0-2) and poor outcome group (>2). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Person correlation analysis was used to determine the correlation between CLEC-2 and HOMA-IR. Multivariate logistic regression analysis was used to determine the correlation between serum CELC-2, HOMA-IR and the outcome after intravenous thrombolysis. Receiver operating characteristic (ROC) curve was used to determine the predictive value of serum CLEC-2 combined with HOMA-IR for poor outcome after intravenous thrombolysis. Results:A total of 100 patients were enrolled (56 males, 56.0%; aged 70.6±10.86 years, range 49-83 years). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 10.00±6.36. Senenty-four patients (74.0%) had a good outcome and 26 (26.0%) had a poor outcome. Person correlation analysis showed that there was a significant positive correlation between serum CLEC-2 and HOMA-IR ( r=0.523; P<0.001). Multivariate logistic regression analysis showed that after adjusting for confounding factors (C-reactive protein, baseline NIHSS score, onset-to-needle time), the highest quartile of serum CLEC-2 (compared with the lowest quartile: odds ratio [ OR] 4.836, 95% confidence interval [ CI] 1.105-21.169; P=0.036) and the highest quartile of HOMA-IR (compared with the quartile 1-3: OR 15, 95% CI 2.647-30.722; P=0.002) were the independent risk factors for the poor outcome in patients with AIS after intravenous thrombolysis. ROC curve analysis showed that the area under the curve for serum CLEC-2 combined with HOMA-IR to predict poor outcome was 0.785 (95% CI 0.688-0.883; P<0.001), the optimal cut-off value was 0.72, and the sensitivity and specificity were 76.0% and 95.0%, respectively. Conclusion:CLEC-2 combined with insulin resistance has a certain predictive value for the poor outcome of patients with AIS after intravenous thrombolysis.
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Objective To study the expression and clinical value of glycogen synthase kinase -3β(GSK-3β),Dickkopf -1(DKK-1) and β-catenin in patients with proximal gastriccancer.Methods FromApril2016 to April 2017,47 patients with proximal gastric cancer in Chengfeng Hospital of Daqing Oilfield Group were enrolled in this study.Immunohistological tests were performed in all patients'lesions,adjacent tissues and healthy tissues .The effects of different factors on the expression of GSK -3βandDKK-1 werecompared.Results Thepositive expression rate of GSK-3βin the normal tissues of patients with proximal gastric cancer was 70.21％(33/47),which was higher than those in the lesions and adjacent tissues [21.28％(10/47),21.28％(10/47)](χ2 =31.985,P<0.01). The positive expression rates of DKK -1 andβ-catenin in the gastric cancer tissues were 38.30％(18/47),82.98％(39/47),respectively,which were higher than those in the adjacent tissues and normal tissues [8.51％(4/47), 8.51％(4/47),and 6.38％(3/47),2.13％(1/47)](χ2 =20.517,88.471,all P<0.01).The GSK-3βpositive expression rate was higher in patients with tumor node metastasis ( TNM) stage I-II,moderately well differentiated , infiltrated more than 50％,non-metastatic lymph nodes (P<0.05).The DKK-1 positive expression rate was higher in patients with TNM stage III-IV,moderately well differentiated and less than 50％ infiltrated lymph nodes ( P<0.05).Conclusion GSK-3β,DKK-1 and β-catenin are important indicators in the development and metastasis of gastric cancer.The above indicators have clinical value in the diagnosis and evaluation of curative effect .
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Objective@#To study the expression and clinical value of glycogen synthase kinase-3β(GSK-3β), Dickkopf-1(DKK-1) and β-catenin in patients with proximal gastric cancer.@*Methods@#From April 2016 to April 2017, 47 patients with proximal gastric cancer in Chengfeng Hospital of Daqing Oilfield Group were enrolled in this study.Immunohistological tests were performed in all patients' lesions, adjacent tissues and healthy tissues.The effects of different factors on the expression of GSK-3β and DKK-1 were compared.@*Results@#The positive expression rate of GSK-3β in the normal tissues of patients with proximal gastric cancer was 70.21% (33/47), which was higher than those in the lesions and adjacent tissues[21.28% (10/47), 21.28%(10/47)](χ2=31.985, P<0.01). The positive expression rates of DKK-1 and β-catenin in the gastric cancer tissues were 38.30% (18/47), 82.98% (39/47), respectively, which were higher than those in the adjacent tissues and normal tissues[8.51% (4/47), 8.51% (4/47), and 6.38% (3/47), 2.13% (1/47)](χ2=20.517, 88.471, all P<0.01). The GSK-3β positive expression rate was higher in patients with tumor node metastasis (TNM) stage I-II, moderately well differentiated, infiltrated more than 50%, non-metastatic lymph nodes (P<0.05). The DKK-1 positive expression rate was higher in patients with TNM stage III-IV, moderately well differentiated and less than 50% infiltrated lymph nodes (P<0.05).@*Conclusion@#GSK-3β, DKK-1 and β-catenin are important indicators in the development and metastasis of gastric cancer.The above indicators have clinical value in the diagnosis and evaluation of curative effect.
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Acute pancreatitis (AP) is an exocrine inflammatory disease of the pancreas, the pathophysiological mechanism of AP remains unclear. Autophagy is an important pathway of metabolic degradation in cells, and autophagy impairment is closely associated with the development and progression of many diseases. Recent studies have found that the process of autophagy is abnormal in AP, with impaired fusion of autophagosome and lysosome and a significant reduction in the degradation function of autolysosome. Abnormal activation of pancreatic enzymes and inflammatory response is the key event in the initiation of AP, and abnormal autophagy is closely associated with these two events. The study of the upstream and downstream mechanisms of autophagy dysfunction in AP may help to find new molecular targets and strategies for the treatment of AP.
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Objective To investigate the relationship between the changes of plasma thromboxane B2 (TXB2),6-keto-prostaglandin 1 α (6k-PGF1 α) and positive platelet α-granule membrane glycoprotein (CD62P) in patients with acute cerebral infarction.Methods 160 patients with acute cerebral infarction (case group) and 80 healthy subjects were enrolled in our hospital from August 2016 to August 2018.The plasma levels of 6k-PGF1α,CD62P and TXB2 were measured and analyzed.Subgroup analysis was performed on patients with cerebral infarction with different trial of org 10172 in acute stroke treatment (TOAST) classification,National Institute of Health Stroke Scale (NIHSS) score,and prognosis outcome.Results The plasma levels of 6k-PGF1α,CD62P and TXB2 in the case group were significantly higher than those in the control group (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in mild,moderate and severe groups were gradually increased (P ＜ 0.05).The plasma levels of 6k-PGF1 α,CD62P and TXB2 in patients with small infarction,mid-infarction and large infarction were also gradually increased,with statistically significant difference (P ＜ 0.05);plasma 6k-PGF1 α,CD62P,TXB2 levels in patients with good prognosis were significantly lower than those in poor prognosis group (P ＜ 0.05).Conclusions The levels of plasma TXB2,6k-PGF1α and CD62P in patients with acute cerebral infarction are elevated,and are closely related to the patient's condition and prognosis.
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The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.
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Abstract Purpose: To investigate the correlation of inhaled nitric oxide (NO) on plasma levels of cardiac troponin I (cTnI) and von Willebrand factor (vWF), glycoprotein (GP) IIb/IIIa, granule membrane protein 140 (GMP-140) in rabbits with acute massive pulmonary embolism (PE). Methods: Thirty apanese white rabbits were divided into 3 groups, thrombus were injected in model group (n = 10), NO were inhalated for 24 h after massive PE in NO group (n = 10), saline were injected in control group (n = 10). The concentrations of vWF, GP IIb/IIIa, GMP-140 and cTnI were tested at 4, 8, 12, 16, 20, and 24 h, Correlation analyses were conducted between cTnI and vWF, GP IIb/IIIa, and GMP-140 by Pearson's correlation. Results: The concentration of cTnI and vWF, GP IIb/IIIa, and GMP-140 was increased in the model group, compared to control group. In the inhaled group, the concentrations of cTnI, vWF, GP IIb/IIIa, and GMP-140 were reduced compared to model group. There was a positive correlation between cTnI and vWF, GP IIb/IIIa, and GMP-140. Conclusion: Inhaled nitric oxide can lead to a decrease in levels of cardiac troponin I, von Willebrand factor, glycoprotein, and granule membrane protein 140, after an established myocardial damage, provoked by acute massive pulmonary embolism.
Subject(s)
Animals , Rabbits , Pulmonary Embolism/blood , von Willebrand Factor/analysis , Platelet Glycoprotein GPIIb-IIIa Complex/analysis , Platelet Glycoprotein GPIIb-IIIa Complex/drug effects , P-Selectin/blood , Troponin I/blood , Nitric Oxide/administration & dosage , Pulmonary Embolism/pathology , Pulmonary Embolism/drug therapy , Reference Values , Time Factors , Administration, Inhalation , von Willebrand Factor/drug effects , Reproducibility of Results , Treatment Outcome , P-Selectin/drug effects , Troponin I/drug effects , Disease Models, Animal , X-Ray Microtomography , Heart Ventricles/pathology , Myocardium/pathologyABSTRACT
The use of organophosphates has been recommended for fish, especially the trichlorfon to control parasites. Colossoma macropomum were exposed to trichlorfon during 96 hours and of total number of mucous cells decreased in the number of cells when compared to the control group. Glycoproteins acid, acid sulphated and neutral was identified in the gill epithelium. Neutra glycoprotein had a significant decrease between control and the sublethal concentration. Acid glycoprotein didn't have any significant difference between the groups exposed to the trichlorfon, compared to the control group. Sulfated acidic glycoprotein in the group exposed to the trichlorfon was noticed a reduction in number of mucosal cells acidic sulphated. The differences between density cell and production glycoprotein was a response of these cells after exposure to xenobiotic. The reduction of neutral, acid and sulphated acid glycoprotein in the MC of the gill epithelium Colossoma macropomum may affect gills epithelial surface protection by reducing the formation of an unstirred layer and enhance the ion loss.(AU)
A utilização de organofosforados tem sido recomendada em pisciculturas, principalmente o trichlorfon, para o controle de parasitoses. Colossoma macropomum foram expostos ao trichlorfon durante 96 horas, e o número total de células mucosas diminuiu no número de células quando comparado com o grupo controle. Glicoproteínas ácida, ácida sulfatada e neutra foram identificadas no epitélio branquial. Glicoproteína neutra teve uma diminuição significativa entre o controle e a concentração subletal. Glicoproteína ácida não apresentou diferença significativa entre os grupos expostos ao triclorfon, em comparação com o grupo controle. Glicoproteína ácida sulfatada no grupo exposto ao triclorfon teve uma redução no número de células da mucosa ácida sulfatada. As diferenças entre a densidade celular e a produção de glicoproteína foi uma resposta dessas células após exposição aos xenobióticos. A redução das glicoproteínas neutra, ácida e ácida sulfatada no epitélio branquial de Colossoma macropomum pode afetar a proteção da superfície, reduzindo a formação de uma camada de muco, e aumentar a perda de íons.(AU)
Subject(s)
Animals , Fishes/metabolism , Glycoproteins/classification , Organophosphorus Compounds/chemical synthesis , FisheriesABSTRACT
PURPOSE: The goal of this study was to purify and characterize Ebola virus glycoprotein (GP)-specific IgG antibodies from hybridoma clones. MATERIALS AND METHODS: For hybridoma production, mice were injected by intramuscular-electroporation with GP DNA vaccines, and boosted with GP vaccines. The spleen cells were used for producing GP-specific hybridoma. Enzyme-linked immunosorbent assay, Western blot assay, flow cytometry, and virus-neutralizing assay were used to test the ability of monoclonal IgG antibodies to recognize GP and neutralize Ebola virus. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity by enzyme-linked immunosorbent assay and the presence of both IgG heavy and light chains by Western blot assay, were chosen as a possible IgG producer. Among these, five clones (C36-1, D11-3, D12-1, D34-2, and E140-2) were identified to secrete monoclonal IgG antibodies. When the monoclonal IgG antibodies from the 5 clones were tested for their antigen specificity, they recognized GP in an antigen-specific and IgG dose-dependent manner. They remained reactive to GP at the lowest tested concentrations (1.953–7.8 ng/mL). In particular, IgG antibodies from clones D11-3, D12-1, and E140-2 recognized the native forms of GP expressed on the cell surface. These antibodies were identified as IgG1, IgG2a, or IgG2b kappa types and appeared to recognize the native forms of GP, but not the denatured forms of GP, as determined by Western blot assay. Despite their GP-binding activity, none of the IgG antibodies neutralized Ebola virus infection in vitro, suggesting that these antibodies are unable to neutralize Ebola virus infection. CONCLUSION: This study shows that the purified IgG antibodies from 5 clones (C36-1, D11-3, D12-1, D34-2, and E140-2) possess GP-binding activity but not Ebola virus-neutralizing activity.
Subject(s)
Animals , Mice , Antibodies , Antibody Formation , Blotting, Western , Clone Cells , Ebolavirus , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Glycoproteins , Hemorrhagic Fever, Ebola , Hybridomas , Immunoglobulin G , In Vitro Techniques , Sensitivity and Specificity , Spleen , Vaccines , Vaccines, DNAABSTRACT
Objective To investigate the application effect of conbercept combined with minimally invasive vitrectomy in the treatment of patients with diabetic retinopathy .Methods From September 2015 to June 2017 , A total of 81 cases (81 eyes) of diabetic retinopathy in the People's Hospital of Changzhi were divided into two groups according to the random number table ,40 cases in the control group treated with 25 G minimally invasive vitrectomy , and 41 cases in the observation group treated with intravitreal injections of conbercept +25G minimally invasive vitrectomy.The filling rate of intraocular fillers,intraocular pressure (IOP),best corrected visual acuity (BCVA),and the change of retinal thickness before and after operation were observed and compared in two groups .The changes of serum levels of stromal cell derived factor -1 ( SDF-1 ) and β2-glycoprotein Ⅰ(β2-GPⅠ) before and after operation and complications were compared between the two groups .Results The filling rate of intraocular fillers in the observation group was 12.20％(5/41),which was lower than that in the control group [30.00％(12/40)],and the difference was statistically significant (χ2 =3.871,P=0.049).Three months after operation ,the BCVA in the observation group was higher than that in the control group ,and the thickness of the retina was smaller than that in the control group,the differences were statistically significant (t1=4.352,P1 =0.000;t2 =9.709,P2 =0.000).The serum levels of β2-GP I and SDF-1 in the observation group were lower than those in the control group at 5 days after operation,and the differences were statistically significant (t1=22.978,P1=0.000;t2=26.875,P2=0.000). The incidence rate of complication in the observation group was 7.32％ (3/41),which was lower than that in the control group 25.00％ (10/40),and the difference was statistically significant (χ2 =4.699,P =0.030). Conclusion Conbercept combined with minimally invasive vitrectomy in the treatment of patients with diabetic retinopathy can reduce the thickness of retina and the serum levels of β2-GP Ⅰ and SDF -1.The filling rate of intraocular fillers in the patients is low ,and it can help to improve the visual function of the patients and reduce the incidence of complications .