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@#Herpes simplex virus(HSV)is a ubiquitous enveloped virus containing double-stranded DNA. HSV-1 infection can cause inflammation of the lips,conjunctivitis and encephalitis,HSV-2 infection can cause genital herpes at many ages,and both viruses can establish lifelong latent infection in the body. Membrane fusion triggered by the interaction of various HSV membrane proteins is an important way for viruses to enter host cells. This review introduced the conserved core fusion mechanism of HSV composed of four viral glycoproteins gD,gH,gL and gB by analyzing the structure of glycoproteins and their interaction modes. Since there is currently no HSV vaccine approved for marketing in the world,it is of great significance to study the mode of action of HSV and host cells for the development of vaccines
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ObjectiveTo investigate the value of serum Fetuin-A and Fetuin-B combined with Homeostasis Model Assessment of Insulin Resistance （HOMA-IR） in predicting nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 120 patients with NAFLD who attended Department of Gastroenterology， The First Affiliated Hospital of Dali University， from June 2020 to June 2021， and 120 healthy individuals who underwent physical examination at Physical Examination Center during the same period of time were enrolled as subjects， and clinical data were collected from all subjects. The serum levels of Fetuin-A and Fetuin-B were measured. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the multivariate Logistic regression analysis was used to assess the risk factors for NAFLD. The receiver operating characteristic （ROC） curve was plotted to evaluate the predictive efficacy of Fetuin-A and Fetuin-B combined with HOMA-IR in NAFLD patients. ResultsCompared with the healthy control group， the NAFLD group had significantly higher levels of body mass index， systolic blood pressure， diastolic blood pressure， alanine aminotransferase， aspartate aminotransferase， fasting blood glucose， fasting insulin， triglycerides， HOMA-IR， Fetuin-A， and Fetuin-B （all P<0.05）. The multivariate Logistic regression analysis showed that Fetuin-A （odds ratio ［OR］=1.010， 95% confidence interval ［CI］： 1.001 — 1.020， P<0.05）， Fetuin-B （OR=1.113， 95%CI： 1.021 — 1.214， P<0.05）， and HOMA-IR （OR=24.053， 95%CI： 2.624 — 220.470， P<0.05） were independent risk factors for NAFLD. The ROC curve analysis showed that Fetuin-A， Fetuin-B or HOMA-IR alone had an area under the ROC curve （AUC） of 0.637 （95%CI： 0.551 — 0.722）， 0.853 （95%CI： 0.796 — 0.912）， and 0.837 （95%CI： 0.763 — 0.912）， respectively， and Fetuin-A combined with Fetuin-B， Fetuin-A combined with HOMA-IR， and Fetuin-B combined with HOMA-IR had an AUC of 0.853 （95%CI： 0.795 — 0.911）， 0.843 （95%CI： 0.770 — 0.916）， 0.922 （95%CI： 0.877 — 0.967）， respectively， while the combination of these three indicators had an AUC of 0.922 （95%CI： 0.877 — 0.966）. ConclusionFetuin-A and Fetuin-B have a certain value in predicting NAFLD， and Fetuin-B combined with HOMA-IR tends to have a higher predictive value.
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Aim To express and purify recombinant hCGH-CTP fusion protein in high-density suspension culture of Chinese hamster ovary cells (CHO-S), and to verify the lipid accumulation effect of rhCGH-CTP on 3T3-L1 mature adipocytes. Methods The recombinant protein expression vector (pcDNA3. 1-rhCGH-CTP) was constructed, achieved by fusing the human glycoprotein hormone beta 5/alpha 2 cDNA with CTP Linker. The expression plasmid was transiently transfected into the suspended CHO-S to express rhCGH-CTP protein and then purified, and the protein biological activity was verified. Intervention with 3T3-L1 mature adipocyte cells for 24 h was performed to detect the changes of intracellular triglyceride (TG) level. Results Western blot results showed that rhCGH-CTP protein was successfully expressed in CHO-S cells, and the yield was up to 715. 4 mg • L~ . The secreted protein was purified by AKTA pure system with higher purity that was up to 90% as identified by SDS-PAGE. In addition, the intracellular cAMP content of mature adipocytes with high expression of TSHR gene significantly increased after intervention with different concentrations of rhCGH-CTP protein by ELISA kit, indicating that rhCGH-CTP protein had biological activity. Oil red 0 staining showed that compared with the control group, the lipid content of mature adipocytes in the intervention groups with different concentrations of rhCGH-CTP protein significantly decreased (P < 0. 05) . Conclusions The rhCGH-CTP protein has been successfully expressed and purified with biological activity, and effectively reduce TG. This research provides an important theoretical basis for further revealing the physiological role of CGH protein and its potential application in clinical practice.
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Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.
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ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.
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@#Objective To express glycoprotein H(gH)of pseudorabies virus(PRV)in mammalian cells and detect its immunogenicity.Methods The gH gene fragment of PRV-XiangA strain was amplified by PCR and inserted into mammalian cell expression vector pIRES-neo3 to construct recombinant expression plasmid pIRES-gH,which was transfected to HEK-293F cells and cultured in suspension for 5 d. The cell culture supernatant was identified by Western blot and purified by nickel ion chromatography column. The purified gH was emulsified with ISA 201 VG adjuvant to immunize 8 female ICR mice,and 8 mice in control group were immunized with the same amount of adjuvant,which was strengthened at 5 and 8weeks after the first dose respectively. The blood samples were collected at 4,7 and 10 weeks after the first dose and detected for the titer of specific antibody and neutralizing antibody in serum of mice;The mice were challenged with PRVXiangA strain(1. 5 × 104TCID50)by nasal drops 2 d after the third blood collection,and observed for the morbidity and mortality daily.Results The recombinant expression plasmid pIRES-gH was constructed correctly as identified by sequencing. The gH protein was successfully expressed and modified by glycosylation in mammalian cells with good reactivity,and about 625 μg purified protein was obtained under 100 mL culture volume. After three times of immunization,mice produced high level of specific antibody and showed the effect of neutralizing PRV,and the titer of neutralizing antibody reached 1∶256. In the challenge test,all the mice in control group became ill and died,while half of the mice in gH immunized group did not get sick with a survival rate of 50%.Conclusion PRV gH was successfully expressed in mammalian cells,and its immune protection was confirmed for the first time,which provided experimental basis for the further research and application of gH,and also provided a new idea for the development of PRV subunit vaccine.
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PURPOSE@#Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.@*METHODS@#The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.@*RESULTS@#For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.@*CONCLUSION@#It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.
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Humans , Anemia/prevention & control , Anticoagulants/therapeutic use , Arthroplasty, Replacement, Knee/adverse effects , ATP Binding Cassette Transporter, Subfamily B/metabolism , Creatinine , Dabigatran/therapeutic use , Hemoglobins , Polymorphism, Genetic , Prospective Studies , Venous Thromboembolism/prevention & controlABSTRACT
Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.
Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.
Subject(s)
Optic Neuritis , Oligodendrocyte-Myelin Glycoprotein , Myelitis , Serology , Magnetic Resonance Imaging , Immunosuppression TherapyABSTRACT
Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.
Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.
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Introduction: In squamous cell carcinoma, cells invade the stroma in the form of islands, strands or sheets, which are surrounded by an extracellular matrix, thus producing reactive changes in the stroma. These reactive changes in the stroma may alter the biological behavior of oral cancer which convey some diagnostic and prognostic significance. Objective: This study was to compare staining intensity of various components of connective tissue such as collagen, elastin and glycoprotein among three histological grades of oral squamous cell carcinoma and normal oral mucosa. Materials and Methods: A total sample of 48 in which 36 cases of histologically diagnosed oral squamous cell carcinoma, 12 each of well, moderate and poorly differentiated squamous cell carcinomas and 12 sections of normal mucosa as the control group were selected for the present study. The sections of tissue blocks were stained with connective tissue specific stains such as Verhoeff’s -VanGieson stain and PAS for collagen, elastin and glycoprotein respectively. Results: Staining intensity of collagen, elastin and glycoprotein around tumor island among different grades of OSCC and normal mucosa revealed statistically significant changes (P value <0.001). Collagen and glycoprotein degradation and elastosis are more prominent in poorly differentiated squamous cell carcinomas. Conclusion: Observable changes were seen in the stroma, in all the three grades of OSCC’s compared to normal mucosa. There was an increased stromal response in poorly differentiated carcinomas, when compared to the other grades. Role of the stroma is like a double-edged sword, at times helping in tumor invasion and otherwise warding off the tumor cells.
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Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.
Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.
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Background: Ca-125 is a large molecular-weight glycoprotein synthesized by different cells originating from the coelomic epithelium. Although classically it has been used to monitor the course of ovarian epithelial cancer, there are other established circumstances associated with high serum Ca -125 levels and pulmonary tuberculosis is one of them. Diagnosing pulmonary tuberculosis, which is not bacteriologically positive often very challenging. Because many procedures are available for such cases but they are of limited use because some of them are lengthy or expensive or need sophisticated equipment, highly skilled personnel, etc. Serum CA-125 is a rapid, relatively inexpensive investigation. Objective: The present study aimed to assess the role of CA-125 in distinguishing pulmonary TB from bacterial pneumonia. Methods: This analytical cross-sectional study was conducted in the Department of Medicine, Dhaka Medical College Hospital for the period of March 2018 to September 2020.100 pulmonary tuberculosis patients were taken in group I, and 100 bacterial pneumonia patients were taken in group II according to selection criteria. Informed written consent was taken from each of the participants. All were subjected to detail clinical and demographic history along with thorough physical examination. Relevant investigations were done including serum CA-125. All final data were collected in the semi-structured and pretested case record form. After data collection, data were checked for errors, and analysis was done. Results: In this study, the mean CA-125 value was 62.29 (SD±31.51) IU/mL in group I(pulmonary tuberculosis). In group II (bacterial pneumonia) mean value was 22.95(±8.25) IU/mL. The mean value of CA-125 was significantly higher (p-value <0.001) in group I patients compared to group II. About 59.0% of patients in group I had a high level of serum CA-125 which had a significant difference from group II (p<0.001). ROC analysis of CA-125 in the diagnosis of patients with active pulmonary tuberculosis showed a cut-off value of ?31.7 IU/mL had sensitivity, specificity, PPV, NPV, PLR, NLR, and accuracy of 72%, 87%, 84.7%, 75.7%, 5.54%, 0.321%, and 79.5% respectively. Conclusion: This study’s findings stated that serum CA-125 may be a useful marker in distinguishing PTB from bacterial pneumonia. Therefore, further study with a more generalized study population is recommended.
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ABSTRACT Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.
RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.
Subject(s)
Humans , Research Design , Optic Neuritis , Immunoglobulin G , Optic Neuritis/drug therapy , Myelin-Oligodendrocyte GlycoproteinABSTRACT
Abstract Objective: To investigate the clinical implications of Golgi glycoprotein 73 (GP73) and granulocyte colony-stimulating factor (G-CSF) in children with bronchopneumonia (BP). Methods: Seventy-two children with BP (observation group) and 81 healthy children (control group) consecutively brought to the present study's hospital between June 2019 and October 2020 were enrolled. GP73 and G-CSF levels were determined to analyze their diagnostic value for pediatric BP. High-sensitivity C-reactive protein (hs-CRP) was also measured. The clinical implications of GP73 and G-CSF in pediatric BP complicated with respiratory failure and their connections with the inflammatory response were discussed. Results: GP73 and G-CSF levels were remarkably higher in the observation group (p< 0.05). The sensitivity and specificity of combined detection (GP73+G-CSF) in predicting pediatric BP were 72.22% and 86.42%, respectively (p < 0.001 ). GP73 and G-CSF, which are closely related to X-ray classification and complications in the observation group, decreased after treatment and were positively correlated with hs-CRP (p < 0.05), especially in children complicated with respiratory failure. Regression analysis identified the independence of the course of the disease, hs-CRP, X-ray classification, GP73, and G-CSF as influencing factors of respiratory failure in children with BP (p < 0.05). Conclusion: GP73 and G-CSF, with elevated levels in children with BP, are strongly linked to disease progression and are independent influencing factors of respiratory failure, which may be the key to diagnosing and treating pediatric BP in the future.
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@#ObjectiveTo develop and verify a double antibody sandwich ELISA for the quantitative detection of varicellazoster virus(VZV)glycoprotein E(gE).MethodsHybridoma cell lines secreting antibody against VZV-gE stably were screened by mouse hybridoma fusion technology,using VZV whole virus antigen as immunogen.The antibody titer in mouse ascites was detected by indirect ELISA.After purified by Hi Trap2=0.995 6,P=0.000 1)。结论 建立的双抗体夹心ELISA法具有良好的准确性、精密性和特异性，可用于VZV疫苗中g E抗原含量的快速检测。 ObjectiveTo develop and verify a double antibody sandwich ELISA for the quantitative detection of varicellazoster virus(VZV)glycoprotein E(gE).MethodsHybridoma cell lines secreting antibody against VZV-gE stably were screened by mouse hybridoma fusion technology,using VZV whole virus antigen as immunogen.The antibody titer in mouse ascites was detected by indirect ELISA.After purified by Hi Trap(TM)Mabselect(TM)Mabselect(TM)Su Re and Hi Trap(TM)Su Re and Hi Trap(TM)Desalting,monoclonal antibodies(m Abs)were analyzed for the purity by 12%SDS-PAGE,detected for the specificity by Western blot,and identified for the subtype by mouse monoclonal antibody typing kit.Capture antibody and enzyme-labeled antibody were screened by epitope superposition test,which were determined for the working concentrations by chessboard titration(capture antibody concentrations were 0.25,0.5,1,2,5 and 10μg/m L,enzyme-labeled antibody dilutions were 1∶500,1∶1 000,1∶2 000,1∶5 000 and 1∶10 000),and then a double antibody sandwich ELISA(DAS-ELISA)was developed for the detection of VZV-gE content.In addition,the linear range,accuracy,precision and specificity of the method were verified.The gE content in the supernatant of 3 batches of CHO-VZV-gE cells cultured in 7 L bioreactor for 1～14 d were detected by the developed method.ResultsFour positive hybridoma cell lines secreting specific antibodies against VZV-gE stably were obtained and named as m Ab-B2,m Ab-11,K9C7 and K9F4.The antibodies in mouse ascites showed titers of10(TM)Desalting,monoclonal antibodies(m Abs)were analyzed for the purity by 12%SDS-PAGE,detected for the specificity by Western blot,and identified for the subtype by mouse monoclonal antibody typing kit.Capture antibody and enzyme-labeled antibody were screened by epitope superposition test,which were determined for the working concentrations by chessboard titration(capture antibody concentrations were 0.25,0.5,1,2,5 and 10μg/m L,enzyme-labeled antibody dilutions were 1∶500,1∶1 000,1∶2 000,1∶5 000 and 1∶10 000),and then a double antibody sandwich ELISA(DAS-ELISA)was developed for the detection of VZV-gE content.In addition,the linear range,accuracy,precision and specificity of the method were verified.The gE content in the supernatant of 3 batches of CHO-VZV-gE cells cultured in 7 L bioreactor for 1～14 d were detected by the developed method.ResultsFour positive hybridoma cell lines secreting specific antibodies against VZV-gE stably were obtained and named as m Ab-B2,m Ab-11,K9C7 and K9F4.The antibodies in mouse ascites showed titers of106～106～107with purities of about 97%after purification,which all specifically bound to VZV whole virus protein with light chains ofκchain and heavy chains of Ig G_(2b),Ig G_1,Ig G_(2b)and Ig G_(2a)respectively.m Ab-B2 was determined as capture antibody and HPR-labeled m Ab-11 as enzyme-labeled antibody with the optimum working concentrations of 1.5μg/m L and 1∶5 000respectively.The internal reference concentration of gE antigen was in the range of 1.95～1 000 ng/m L,which showed a good linear relationship with A_(450).The four-parameter equation was Y=(0.15-3.99)/[1+(X/67.4)7with purities of about 97%after purification,which all specifically bound to VZV whole virus protein with light chains ofκchain and heavy chains of Ig G_(2b),Ig G_1,Ig G_(2b)and Ig G_(2a)respectively.m Ab-B2 was determined as capture antibody and HPR-labeled m Ab-11 as enzyme-labeled antibody with the optimum working concentrations of 1.5μg/m L and 1∶5 000respectively.The internal reference concentration of gE antigen was in the range of 1.95～1 000 ng/m L,which showed a good linear relationship with A_(450).The four-parameter equation was Y=(0.15-3.99)/[1+(X/67.4)(1.49)]+3.99,and R(1.49)]+3.99,and R2value was 0.999.The recoveries of accuracy verification were 94.9%～114.0%;The coefficients of variation(CVs)of precision verification were all less than 15%.Except CHO-VZV-gE cell culture supernatant,attenuated live varicella vaccine and attenuated live herpes zoster vaccine,the A_(450)of other samples were all less than 0.15 with no cross reaction.The content of gE in the supernatant of three batches CHO-VZV-gE cells increased gradually with the culture time,and was positively related with culture time within 14 days(R2value was 0.999.The recoveries of accuracy verification were 94.9%～114.0%;The coefficients of variation(CVs)of precision verification were all less than 15%.Except CHO-VZV-gE cell culture supernatant,attenuated live varicella vaccine and attenuated live herpes zoster vaccine,the A_(450)of other samples were all less than 0.15 with no cross reaction.The content of gE in the supernatant of three batches CHO-VZV-gE cells increased gradually with the culture time,and was positively related with culture time within 14 days(R2=0.995 6,P=0.000 1).ConclusionThe developed double antibody sandwich ELISA had good accuracy,precision and specificity,which might be used for rapid detection of gE antigen content in VZV vaccine.
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OBJECTIVE@#To explore the effect of leucine-rich α-2-glycoprotein (LRG1) derived from hepatocytes on activation of hepatic M1 Kupffer cells.@*METHODS@#A metabolic dysfunction-associated fatty liver disease (MAFLD) model was established in BALB/c mice by high-fat diet (HFD) feeding for 16 weeks. Oleic acid was used to induce steatosis in primary cultures of mouse hepatocytes. The mRNA and protein expressions of LRG1 in mouse liver tissues and hepatocytes were detected by real-time PCR and Western blotting. Primary hepatic macrophages were stimulated with the conditioned medium (CM) from steatotic hepatocyte along with LRG1 or transforming growth factor-β1 (TGF-β1), or both for 24 h, and the expression levels of inducible nitric oxide synthase (iNOS) was detected with Western botting, and the mRNA expressions of iNOS, chemokine ligand 1 (CXCL-1) and interleukin-1β (IL-1β) were measured by RT-PCR. The MAFLD mice were injected with LRG1 (n=6), TGF-β1 (n=6), or both (n=6) through the caudal vein, and the live tissues were collected for HE staining and immumohistochemical detection of F4/80 expression; the mRNA expressions of iNOS, CXCL-1 and IL-1β in liver tissues were detected using RT-PCR.@*RESULTS@#The mRNA and protein expression levels of LRG1 were significantly downregulated in the liver tissues of MAFLD mice and steatotic hepatocytes (P < 0.05). Treatment of the hepatic macrophages with CM from steatosis hepatocytes significantly enhanced the mRNA expression levels of iNOS, CXCL-1 and IL-1β, and these changes were significantly inhibited by the combined treatment with TGF-β1 and LRG1 (P < 0.05). In MAFLD mice, injections with either LRG1 or TGF-β1 alone reduced hepatic lipid deposition and intrahepatic macrophage infiltration, and these effects were significantly enhanced by their combined treatment, which also more strongly inhibited the mRNA expression levels of iNOS, CXCL-1 and IL-1β (P < 0.05).@*CONCLUSION@#LRG1 inhibits hepatic macrophage infiltration by enhancing TGF-β1 signaling to alleviate fatty liver inflammation in MAFLD mice.
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Animals , Mice , Transforming Growth Factor beta1 , Macrophage Activation , Signal Transduction , Non-alcoholic Fatty Liver Disease , Culture Media, Conditioned , GlycoproteinsABSTRACT
OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.
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AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P<0.01). The expression of p-STAT3 and VEGF-A in sgp130 group were lower than those in DM group(all P<0.01).CONCLUSION: The sgp130 can selectively antagonize the trans signal transduction pathway of IL-6, down-regulate the expression of downstream inflammatory factors VEGF-A, and it may be used in the intervention of retinal inflammatory damage related with IL-6 in DM.
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Objective:To investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity.Methods:A cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. Results:The CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm 2, (57.78±12.35) root/mm 2, (3.27±1.34) mm/mm 2, and (13.74±3.05) mm/mm 2, (70.95±13.14) root/mm 2, and (4.22±1.03) mm/mm 2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant ( t=4.089, 3.795, 2.773; P<0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm 2, (3.80±1.19) mm/mm 2, (47.97±8.86) fibers/mm 2, and (9.25±2.19) mm/mm 2, (2.72±1.19) mm/mm 2, (39.43±13.86) fibers/mm 2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant ( t=-4.002, -2.706, -2.306; P<0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm 2, respectively. The difference in corneal DC density between the two subgroups was statistically significant ( P<0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON ( r=-0.422, -0.456; P<0.05). Conclusions:There are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.
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Objective:To study the clinical characteristics and prognosis of Brucella and other pathogens infections complicated with anti-myelin oligodendrocyte glycoprotein-IgG associated disorders (MOGAD). Methods:The clinical data of a patient with brucellosis complicated with MOGAD diagnosed in the Department of Neurology of the First Affiliated Hospital of Zhengzhou University in April 2022 were reported, and related case reports of infection coexisting with MOGAD were reviewed and summarized.Results:This case was a 44-year-old male, with recurrent fever and anorexia, followed by sudden weakness, numbness, pain in both lower limbs and dysuria, and then pain in the right neck. Magnetic resonance imaging showed lesions in the spine and spinal cord. Due to the positive myelin oligodendrocyte glycoprotein antibodies in cerebrospinal fluid and serum, and the growth of Brucella in blood culture, he was diagnosed as brucellosis complicated with MOGAD. After anti-brucellosis and glucocorticoid therapy, his symptoms improved. The literature on infection coexisting with MOGAD was reviewed and 22 cases were included. The infection sources included COVID-19, Borrelia burgdorferi, etc. No case of Brucella infection complicated with MOGAD had been reported. The main clinical manifestations of the 22 cases included myelitis (63.6%, 14/22), optic neuritis (40.9%, 9/22), acute disseminated encephalomyelitis (18.2%, 4/22), multiphasic disseminated encephalomyelitis (4.5%, 1/22) and meningoencephalitis (4.5%, 1/22). Magnetic resonance imaging was performed in 20 cases, showing spinal cord lesions in 12 cases (60.0%, 12/20), intracranial lesions in 10 cases (50.0%, 10/20) and optic nerve lesions in 6 cases (30.0%, 6/20). Cerebrospinal fluid examination was performed in 19 patients, of whom 13 (13/19) had increased cerebrospinal fluid cell count and 10 (10/18) had increased cerebrospinal fluid protein. Twenty-two patients received glucocorticoid therapy, of which 95.5% (21/22) responded well and 95.5% (21/22) had a good prognosis. Conclusions:Brucella and other pathogens infection may complicate with MOGAD, with similar clinical manifestations, and glucocorticoid therapy is effective.