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1.
Journal of Zhejiang University. Science. B ; (12): 51-64, 2024.
Article in English | WPRIM | ID: wpr-1010597

ABSTRACT

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.


Subject(s)
Humans , Glycosylation , Pancreatic Neoplasms/pathology , Adenocarcinoma , Proto-Oncogene Proteins p21(ras)/metabolism , Glycoproteins , Mass Spectrometry , Biomarkers/metabolism , Polysaccharides
2.
J. venom. anim. toxins incl. trop. dis ; 30: e20230046, 2024. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1528980

ABSTRACT

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and ß), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.


Subject(s)
Animals , Scorpion Venoms/analysis , Scorpion Venoms/chemistry , Peptide Hydrolases , Phospholipases , Glycoproteins , Hyaluronoglucosaminidase
3.
Journal of Southern Medical University ; (12): 1164-1171, 2023.
Article in Chinese | WPRIM | ID: wpr-987033

ABSTRACT

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.


Subject(s)
Animals , Mice , Transforming Growth Factor beta1 , Macrophage Activation , Signal Transduction , Non-alcoholic Fatty Liver Disease , Culture Media, Conditioned , Glycoproteins
4.
Chinese Journal of Obstetrics and Gynecology ; (12): 833-837, 2023.
Article in Chinese | WPRIM | ID: wpr-1012292

ABSTRACT

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-β2 glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×109/L vs (227±37)×109/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) μmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-β2 glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.


Subject(s)
Pregnancy , Female , Humans , Autoantibodies , Antibodies, Antinuclear , Antibodies, Antiphospholipid , Fibrinogen , Homocysteine , Glycoproteins
5.
Chinese Journal of Hepatology ; (12): 495-503, 2023.
Article in Chinese | WPRIM | ID: wpr-986159

ABSTRACT

Objective: To study using isotope-labeled relative and absolute quantitative proteomics methodologies to screen for salivary biological markers as a simple, non-invasive tool for identifying hepatitis B-related HCC at an early stage. Methods: Saliva samples were collected to extract salivary proteins. Isotope-labeled relative and absolute quantitative proteomics were used to analyze the differentially expressed proteins between the hepatocellular carcinoma (HCC) and non-HCC groups. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were used to verify differential proteins and identify markers in liver cancer tissues and saliva. Statistical analysis was used to analyze the diagnostic efficiency of salivary biomarkers. Results: 152 differentially expressed salivary proteins were screened out between the HCC and non-HCC groups. Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays validated that the expressions of α-1-acid glycoprotein 1 (ORM1) and alpha-fetoprotein (AFP) were significantly increased in HCC (P < 0.05). There was a significant correlation between salivary AFP and serum AFP (P < 0.05). HCC was diagnosed when salivary α-1-acid glycoprotein 1 combined with AFP. The area under the receiver operating characteristic curve was 0.8726 (95% confidence interval: 0.8104 ~ 0.9347), the sensitivity was 78.3%, and the specificity was 88%. Conclusion: Salivary AFP and α-1-acid glycoprotein 1 can serve as potential biomarkers for hepatitis B-related hepatocellular carcinoma.


Subject(s)
Humans , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/pathology , alpha-Fetoproteins/metabolism , Biomarkers , Hepatitis B , ROC Curve , Glycoproteins , Biomarkers, Tumor
6.
Chinese Journal of Pediatrics ; (12): 606-613, 2023.
Article in Chinese | WPRIM | ID: wpr-985917

ABSTRACT

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.


Subject(s)
Child , Male , Humans , Female , Child, Preschool , Adolescent , Crohn Disease , Inflammatory Bowel Diseases , Colon , Inflammation , Colonoscopy , Glycoproteins , Wnt Proteins
7.
Chinese Journal of Medical Genetics ; (6): 202-207, 2023.
Article in Chinese | WPRIM | ID: wpr-970905

ABSTRACT

OBJECTIVE@#To analyze the correlation between the mRNA levels of breast cancer resistance protein (BCRP) and lung-specific X protein (LUNX) genes with pathological types and stages of patients with non-small cell lung cancer (NSCLC) and their significance for prognosis.@*METHODS@#Eighty nine patients with NSCLC admitted to Huaihe Hospital of Henan University between June 2015 and June 2018 were recruited, with 55 patients with benign lung lesions admitted during the same period of time selected as the control group. The mRNA levels of BCRP and LUNX genes were detected in the peripheral blood samples from the two groups, and their correlation with the clinicopathological characteristics and prognosis of the patients was analyzed.@*RESULTS@#The expression rates of BCRP and LUNX mRNA in the NSCLC group were significantly higher compared with the control group (P < 0.05). The level of BCRP mRNA of the NSCLC patients has correlated with the degree of differentiation and TNM staging (P < 0.05), but not with gender, age, smoking, pathological types and lymph node metastasis (P > 0.05). The level of LUNX mRNA of them has correlated with the degree of differentiation, TNM staging and lymph node metastasis (P < 0.05), but not with gender, age, smoking, and pathological types (P > 0.05). Compared with those with no expression, the overall survival rate of patients with BCRP and LUNX expression was significantly lower (P < 0.05). The degree of differentiation, TNM staging, lymph node metastasis, and expression of the BCRP and LUNX mRNA may all affect the prognosis of the patients.@*CONCLUSION@#The levels of BCRP and LUNX mRNA in the peripheral blood of patients with NSCLC are significantly increased. The expression of BCRP mRNA is correlated with the degree of differentiation and TNM staging, whilst the expression of LUNX mRNA is correlated with the differentiation degree, TNM staging and lymph node metastasis. Both may be used as independent predictors for the prognosis of patients with NSCLC.


Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Glycoproteins/genetics , Lung Neoplasms/pathology , Lymphatic Metastasis , Neoplasm Proteins/genetics , Phosphoproteins/genetics , Prognosis , RNA, Messenger/genetics
8.
Journal of Southern Medical University ; (12): 206-212, 2023.
Article in Chinese | WPRIM | ID: wpr-971516

ABSTRACT

OBJECTIVE@#To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD).@*METHODS@#Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins.@*RESULTS@#In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa.@*CONCLUSION@#Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.


Subject(s)
Humans , Mice , Animals , Caco-2 Cells , beta Catenin/metabolism , Culture Media, Conditioned/pharmacology , Tight Junctions/metabolism , Intestinal Mucosa , Inflammatory Bowel Diseases , Tight Junction Proteins/metabolism , Inflammation/metabolism , Fibroblasts/metabolism , Mice, Inbred C57BL , Glycoproteins/metabolism , Wnt Proteins/pharmacology , Frizzled Receptors/metabolism
9.
Arq. Asma, Alerg. Imunol ; 6(2): 151-169, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400194

ABSTRACT

O angioedema hereditário é uma doença autossômica dominante caracterizada por crises recorrentes de edema que acometem o tecido subcutâneo e o submucoso, com envolvimento de diversos órgãos. Os principais locais afetados são face, membros superiores e inferiores, as alças intestinais e as vias respiratórias superiores. Em decorrência da falta de conhecimento dessa condição por profissionais de saúde, ocorre atraso importante no seu diagnóstico, comprometendo a qualidade de vida dos indivíduos afetados. Além disso, o retardo no diagnóstico pode resultar em aumento da mortalidade por asfixia devido ao edema de laringe. A natureza errática das crises com variação do quadro clínico e gravidade dos sintomas entre diferentes pacientes, e no mesmo paciente ao longo da vida, se constitui em desafio no cuidado dos doentes que têm angioedema hereditário. O principal tipo de angioedema hereditário é resultante de mais de 700 variantes patogênicas do gene SERPING1 com deficiência funcional ou quantitativa da proteína inibidor de C1, porém nos últimos anos outras mutações foram descritas em seis outros genes. Ocorreram avanços importantes na fisiopatologia da doença e novas drogas para o tratamento do angioedema hereditário foram desenvolvidas. Nesse contexto, o Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) em conjunto com a Associação Brasileira de Alergia e Imunologia (ASBAI) atualizou as diretrizes brasileiras do angioedema hereditário. O maior conhecimento dos diversos aspectos resultou na divisão das diretrizes em duas partes, sendo nessa primeira parte abordados a definição, a classificação e o diagnóstico.


Hereditary angioedema is an autosomal dominant disease characterized by recurrent attacks of edema that affect the subcutaneous tissue and the submucosa, involving several organs. The main affected sites are the face, upper and lower limbs, gastrointestinal tract, and upper airways. Because health professionals lack knowledge about this condition, there is a significant delay in diagnosis, compromising the quality of life of affected individuals. Furthermore, delayed diagnosis may result in increased mortality from asphyxia due to laryngeal edema. The erratic nature of the attacks with variations in clinical course and severity of symptoms among different patients and in one patient throughout life constitutes a challenge in the care of patients with hereditary angioedema. The main type of hereditary angioedema results from more than 700 pathogenic variants of the SERPING1 gene with functional or quantitative deficiency of the C1 inhibitor protein, but in recent years other mutations have been described in six other genes. Important advances have been made in the pathophysiology of the disease, and new drugs for the treatment of hereditary angioedema have been developed. In this context, the Brazilian Study Group on Hereditary Angioedema (GEBRAEH) in conjunction with the Brazilian Association of Allergy and Immunology (ASBAI) updated the Brazilian guidelines on hereditary angioedema. Greater knowledge of different aspects resulted in the division of the guidelines into two parts, with definition, classification, and diagnosis being addressed in this first part.


Subject(s)
Humans , Therapeutics , Classification , Diagnosis , Angioedemas, Hereditary , Quality of Life , Asphyxia , Signs and Symptoms , Societies, Medical , Pharmaceutical Preparations , Glycoproteins , Laryngeal Edema , Allergy and Immunology , Mutation
10.
Chinese Medical Journal ; (24): 806-812, 2022.
Article in English | WPRIM | ID: wpr-927521

ABSTRACT

BACKGROUND@#The first-line treatment for lung cancer is surgical resection, and one-lung ventilation (OLV) is the most basic anesthetic management method in lung surgery. During OLV, inflammatory cytokines are released in response to the lung tissue damage and promote local and contralateral lung damage through the systemic circulation. We designed a randomized, prospective study to evaluate the effect of the urinary trypsin inhibitor (UTI) ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer.@*METHODS@#Adult patients aged 19 to 70 years, who were scheduled for video-assisted thoracic lobectomy surgery to treat lung cancer between May 2020 and August 2020, were enrolled in this randomized, prospective study. UTI (300,000 units) mixed with 100 mL of normal saline in the ulinastatin group and 100 mL of normal saline in the control group was administered over 1 h after inducing anesthesia.@*RESULTS@#The baseline (T0) interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio was not different between the groups (6941.3 ± 2778.7 vs. 6954.3 ± 2752.4 pg/mL, respectively; P  > 0.05). The IFN-γ/IL-4 ratio was significantly higher in ulinastatin group at 30 min after entering the recovery room than control group (20,148.2 ± 5054.3 vs. 6674.0 ± 2963.6, respectively; adjusted P < 0.017).@*CONCLUSION@#Administering UTI attenuated the anti-inflammatory response, in terms of INF-γ expression and the IFN-γ/IL-4 ratio, after video-assisted thoracic surgery in lung cancer patients.@*TRIAL REGISTRATION@#Clinical Research Information Service of Korea National Institute of Health (CRIS), KCT0005533.


Subject(s)
Adult , Humans , Glycoproteins , Interleukin-4 , Lung Neoplasms/surgery , Prospective Studies , Saline Solution , Thoracic Surgery, Video-Assisted
11.
Journal of Forensic Medicine ; (6): 468-472, 2022.
Article in English | WPRIM | ID: wpr-984137

ABSTRACT

OBJECTIVES@#To investigate the effects of injury time, postmortem interval (PMI) and postmortem storage temperature on mRNA expression of glycoprotein non-metastatic melanoma protein B (Gpnmb), and to establish a linear regression model between Gpnmb mRNA expression and injury time, to provide aimed at providing potential indexes for injury time estimation.@*METHODS@#Test group SD rats were anesthetized and subjected to blunt contusion and randomly divided into 0 h, 4 h, 8 h, 12 h, 16 h, 20 h and 24 h groups after injury, with 18 rats in each group. After cervical dislocation, 6 rats in each group were collected and stored at 0 ℃, 16 ℃ and 26 ℃, respectively. The muscle tissue samples of quadriceps femoris injury were collected at 0 h, 12 h and 24 h postmortem at the same temperature. The grouping method and treatment method of the rats in the validation group were the same as above. The expression of Gpnmb mRNA in rat skeletal muscle was detected by RT-qPCR. The Pearson correlation coefficient was used to evaluate the correlation between Gpnmb mRNA expression and injury time, PMI, and postmortem storage temperature. SPSS 25.0 software was used to construct a linear regression model, and the validation group data was used for the back-substitution test.@*RESULTS@#The expression of Gpnmb mRNA continued to increase with the prolongation of injury time, and the expression level was highly correlated with injury time (P<0.05), but had little correlation with PMI and postmortem storage temperature (P>0.05). The linear regression equation between injury time (y) and Gpnmb mRNA relative expression (x) was y=0.611 x+4.489. The back-substitution test proved that the prediction of the model was accurate.@*CONCLUSIONS@#The expression of Gpnmb mRNA is almost not affected by the PMI and postmortem storage temperature, but is mainly related to the time of injury. Therefore, a linear regression model can be established to infer the time of injury.


Subject(s)
Animals , Rats , Glycoproteins , Linear Models , Melanoma , Membrane Glycoproteins/genetics , Postmortem Changes , Rats, Sprague-Dawley , RNA, Messenger/metabolism , Time Factors
12.
ABCD (São Paulo, Impr.) ; 34(2): e1585, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1345003

ABSTRACT

ABSTRACT Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.


RESUMO Racional: CD133 e AXL são descritos na literatura como marcadores de células-tronco tumorais, e c-MYC cumpre papel chave como mecanismo de regulação celular no câncer colorretal (CCR). Objetivo: Avaliar o papel prognóstico dos biomarcadores CD133, AXL e c-MYC e sua associação com características clinicopatológicas de adenocarcinomas e adenomas colorretais. Métodos: Um total de 156 pacientes com adenocarcinomas de estádio UICC I-IV (n=122) e adenomas (n=34) colorretais foram avaliados. Microarranjos teciduais (TMA) dos tumores primários e adenomas foram realizados em busca de expressão de CD133, c-MYC e AXL, com posterior análise de relação significativa com características clinicopatológicas. Resultados: Adenocarcinomas pobremente diferenciados e progressão de doença foram fatores de risco independentes para má sobrevida global. A taxa mediana de sobrevida global foi de 30 meses. Expressão positiva de CD133 (35,9% dos casos), particularmente em cânceres de cólon direito (44,8% dos casos CD133+), correlacionou-se negativamente com óbito na análise univariada, sem significância estatística na análise multivariada. c-MYC (15,4% dos casos) teve predomínio de expressão em pacientes com estádio avançado com metástases distantes (não-pulmonares/não-hepáticas). Expressão de AXL foi pouco encontrada, com predomínio em adenomas, com menor penetrância em displasia de alto grau. Conclusão: Expressão de CD133 não se associou com sobrevida global inferior em CCR. Enquanto AXL demonstrou resultados inconclusivos, expressão de c-MYC em tumores primários se associou-se à metástases à distância.


Subject(s)
Humans , Colorectal Neoplasms , Biomarkers, Tumor , Peptides , Prognosis , Neoplastic Stem Cells , Glycoproteins , Antigens, CD , AC133 Antigen
13.
Acta Academiae Medicinae Sinicae ; (6): 25-31, 2021.
Article in Chinese | WPRIM | ID: wpr-878693

ABSTRACT

Objective To summarize clinical characteristics and investigate possible pathogenic gene of Klippel-Feil syndrome(KFS)by the self-designed multigene panel sequencing,so as to decipher the molecular basis for early diagnosis and targeted therapy.Methods From January 2015 to December 2018,we consecutively recruited 25 patients who were diagnosed with KFS in Peking Union Medical College Hospital.The demographic information,clinical manifestations,physical examination and radiological assessments were analyzed.Multigene panel sequencing was performed after DNA extraction from peripheral blood.The possible pathogenic mutations of KFS were explored on the basis of bioinformatics analysis.Results The KFS cohort consisted of 25 patients,including 15 males and 10 females,with a mean age of(12.9±7.3)years.Limited cervical range of motion was the most common clinical feature(12 cases,48%).Based on the Samartzis classification,the proportion of patients suffered from short neck(P=0.031)and limited cervical range of motion(P=0.026)in type Ⅲ KFS was significantly higher than that in type Ⅱ and type Ⅰ KFS.Panel sequencing detected a total of 11 pathogenic missense mutations in eight patients,including COL6A1,COL6A2,CDAN1,GLI3,FLNB,CHRNG,MYH3,POR,and TNXB.There was no pathogenic mutation found in five reported pathogenic genes(GDF6,MEOX1,GDF3,MYO18B and RIPPLY2)associated with KFS.Conclusions Our study has shown that patients with multiple contiguous cervical fusions are more likely to manifest short neck,limited cervical range of motion,and clinical triad.Therefore,these patients need additional attention and follow-up.Our analysis highlights novel KFS-related genetic variants,such as COL6A and CDAN1,extending the spectrum of known mutations contributing to this syndrome and providing a basis for elucidating the pathogenesis of KFS.


Subject(s)
Child , Female , Humans , Male , Cervical Vertebrae , Cohort Studies , Glycoproteins , Klippel-Feil Syndrome/genetics , Mutation , Nuclear Proteins , Radiography , Transcription Factors/genetics
14.
Acta Academiae Medicinae Sinicae ; (6): 371-381, 2021.
Article in Chinese | WPRIM | ID: wpr-887869

ABSTRACT

Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With


Subject(s)
Humans , Biomarkers, Tumor/genetics , Carrier Proteins , Computational Biology , Cytochrome P-450 CYP2E1 , Cytochrome P-450 CYP3A , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Glycoproteins , Liver Neoplasms/genetics , Prognosis , Protein Interaction Maps
15.
Journal of Central South University(Medical Sciences) ; (12): 1063-1070, 2021.
Article in English | WPRIM | ID: wpr-922585

ABSTRACT

OBJECTIVES@#The biomarkers targeting colorectal cancer (CRC) prognosis are short of high accuracy and sensitivity in clinic. Through bioinformatics analysis, we aim to identify and confirm a series of key genes referred to the diagnosis and prognosis of CRC.@*METHODS@#GSE31905, GSE35279, and GSE41657 were selected as complete RNA sequencing data sets of CRC and colorectal mucosa (CRM) tissues from the NCBI-GEO database, and the differentially expressed genes (DEGs) were analyzed. The common DEGs in these 3 data sets were obtained by Venn map, and enriched by STRING network system and Cytoscape software. The Kaplan-Meier plotter website was used to verify the correlation between the enriched genes and the prognosis of CRC.@*RESULTS@#For the whole RNA sequencing data sets of CRC and normal intestinal mucosa samples, the DEGs of CRC and CRM in the 3 data sets (|log@*CONCLUSIONS@#The above 11 genes verified by bioinformatics retrieval and analysis can predict the poor prognosis of CRC to a certain extent, and they provide a possible target for the diagnosis and treatment of CRC.


Subject(s)
Humans , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Computational Biology , Formins , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Glycoproteins , Intercellular Signaling Peptides and Proteins , Oncogenes , Prognosis , Protein Interaction Maps
16.
Pesqui. vet. bras ; 40(12): 1073-1076, Dec. 2020. tab
Article in English | LILACS, VETINDEX | ID: biblio-1155038

ABSTRACT

Bronchoalveolar lavage fluid (BALF) was analyzed to obtain information on leakage of acute-phase proteins from the blood into the respiratory lumen and about local synthesis. Ceruloplasmin, transferrin, albumin, α1-antitripsin, immunoglobulin G heavy, immunoglobulin G light, immunoglobulin A, haptoglobin, acidic glycoprotein, and P23 were measured in BALF from 30 horses without inflammatory disease by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In serum, the same proteins were identified except for α1-antitrypsin. In conclusion, this study demonstrated that polyacrylamide gel electrophoresis (SDS-PAGE) can be used for the determination of acute-phase proteins in BALF samples from horses. In healthy horses, the values are very low, but they can be compared with reference values to assist in the diagnosis of animals with respiratory diseases.(AU)


O líquido obtido através da lavagem broncoalveolar (LBA) foi analisado para obter informações sobre as proteínas da fase aguda. Ceruloplasmina, transferrina, albumina, α1-antitripsina, imunoglobulina G pesada, imunoglobulina G leve, imunoglobulina A, haptoglobina, glicoproteína ácida e P23 foram medidas nos LBA de 30 cavalos sem doença inflamatória por eletroforese em gel de poliacrilamida com dodecilsulfato de sódio (SDS-PAGE). No soro, as mesmas proteínas foram identificadas, exceto a α1-antitripsina. Em conclusão, este estudo demonstra que a eletroforese em gel de poliacrilamida (SDS-PAGE) pode ser usada para a determinação de proteínas de fase aguda em amostras de LBA em cavalos. Em cavalos saudáveis, os valores são muito baixos, no entanto, podem ser comparados e auxiliar no diagnóstico de animais com doenças respiratórias.(AU)


Subject(s)
Animals , Biomarkers/analysis , Acute-Phase Reaction/diagnosis , Bronchoalveolar Lavage/veterinary , Electrophoresis, Polyacrylamide Gel , Horses , Ceruloplasmin , Haptoglobins , Immunoglobulin A , Immunoglobulin G , Glycoproteins
17.
Arq. bras. med. vet. zootec. (Online) ; 72(3): 703-710, May-June, 2020. ilus, graf
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1128856

ABSTRACT

O herpesvírus equídeo 1 (EHV-1) apresenta distribuição mundial e causa graves prejuízos à equideocultura. É agente de surtos de doença respiratória, reprodutiva e neurológica, em equídeos jovens e adultos. A glicoproteína D (gD) do envelope viral é essencial para ligação e penetração em células permissivas e direcionamento do sistema imunológico do hospedeiro, induz respostas imunes humorais e celulares, sendo um antígeno apropriado para ser utilizado em vacinas e imunodiagnóstico. O objetivo deste trabalho foi expressar e caracterizar a gD do EHV-1 em Pichia pastoris para posterior utilização como antígeno em técnicas de imunodiagnóstico e formulação de vacinas recombinantes. Uma sequência de DNA que codifica uma forma truncada da gDEHV-1 foi clonada no vetor pPICZαA de expressão em P. pastoris. Obteve-se uma proteína de ~41 kDa, como esperado. A proteína apresentou glicosilação entre 4 kDa e 16 kDa, demonstrada por deglicosilação enzimática. A proteína recombinante foi caracterizada antigenicamente e imunogenicamente por Western blot, utilizando-se anticorpos policlonais equinos anti-EHV-1, e por ELISA indireto em modelo murino, demonstrando que a gD recombinante manteve epítopos similares aos da proteína nativa. Esses resultados sugerem que a gDEHV-1 é um antígeno promissor para uso como imunobiológico no controle do EHV-1.(AU)


Equine herpesvirus 1 (EHV-1) has a worldwide distribution and causes serious damage to horse breeding. It is an agent of respiratory, reproductive and neurological disease outbreaks in young and adult equids. Viral envelope glycoprotein D (gD) is essential for binding and penetration into permissive cells and targeting the host immune system, inducing humoral and cellular immune responses, and is an appropriate antigen for use in vaccines and immunodiagnostics. The objective of this work was to express in Pichia pastoris and to characterize EHV-1 gD for later use as an antigen in immunodiagnostic techniques and formulation of recombinant vaccines. A DNA sequence encoding a truncated form of gDEHV-1 has been cloned into the P. pastoris expression vector pPICZαA. A protein of ~41 kDa was obtained as expected. The protein presented glycosylation between 4 kDa and 16 kDa, demonstrated by enzymatic deglycosylation. The recombinant protein was antigenically and immunogenically characterized by Western blot using equine polyclonal anti-EHV-1 antibodies, and by indirect ELISA in a murine model, demonstrating that the recombinant gD maintained epitopes similar to those of the native protein. These results suggest that gDEHV-1 is a promising antigen for use as an immunobiological in the control of EHV-1.(AU)


Subject(s)
Animals , Pichia/isolation & purification , Glycoproteins , Herpesvirus 1, Equid/isolation & purification , Respiratory Tract Diseases/veterinary , Horses/virology
18.
Arq. Inst. Biol ; 87: e0012020, 2020.
Article in English | VETINDEX, LILACS | ID: biblio-1130112

ABSTRACT

Caprine herpesvirus 1 (CpHV-1) infection is associated with clinical manifestations related to animal age, with high mortality in kids and infertility in adults. Given the scarcity of research about the epidemiological situation of this infection in Brazilian flocks, we aimed to conduct a cross-sectional descriptive study to detect antibodies against CpHV-1 in goats in the state of São Paulo, Brazil. Fifty-five male and female goats ­ kids and adult ­ were assessed in this study. Blood serum was analyzed by a commercial ELISA kit to detect antibodies against CpHV-1, which had not been used in Brazil before. No animals were reactive. Brazil lacks information about CpHV-1 infection in goat flocks. Continuing the study is crucial to understand the epidemiological situation of the disease and establish protocols for infection control.(AU)


A infecção pelo Herpesvírus Caprino tipo 1 (CpHv-1) está associada a manifestações clínicas relacionadas à idade dos animais, com alta mortalidade em filhotes e infertilidade em adultos. Diante da escassez de estudos sobre situação epidemiológica dessa infecção nos rebanhos brasileiros, a presente pesquisa teve como objetivo realizar um estudo transversal e descritivo para a detecção de anticorpos anti-Herpesvírus Caprino tipo 1 em caprinos do estado de São Paulo, Brasil. Foram avaliados 55 caprinos machos e fêmeas, filhotes e adultos. O soro sanguíneo foi analisado por um kit ELISA comercial para detecção de anticorpos contra CpHv-1, de utilização inédita no Brasil. Nenhum animal estudado foi sororreagente. O Brasil carece de informações acerca da infecção pelo Herpesvírus Caprino tipo 1 nos rebanhos caprinos do país. A continuidade do estudo é imprescindível para compreender a situação epidemiológica da enfermidade e estabelecer protocolos para controle da infecção.(AU)


Subject(s)
Animals , Male , Female , Peptides/immunology , Goats/virology , Glycoproteins/immunology , Varicellovirus/immunology , Herpesviridae Infections/diagnosis , Ruminants/virology , Enzyme-Linked Immunosorbent Assay/methods , Cross-Sectional Studies , Varicellovirus/isolation & purification , Herpesviridae Infections/immunology
19.
Journal of Southern Medical University ; (12): 1184-1191, 2020.
Article in Chinese | WPRIM | ID: wpr-828916

ABSTRACT

OBJECTIVE@#To construct a HIV-1 gp120 transgenic mouse model (gp120) with 7 nicotinic acetylcholine receptor (7nAChR) gene knockout.@*METHODS@#The 7nAChR gene knockout mice (7R) were crossed with HIV-1gp120 transgenic mice (gp120) to generate F1 generation mice. We selected the F1 mice with the genotype of 7R/gp120 to mate to obtain the F2 mice. The genotypes of the F3 mice were identified by PCR, and the protein expressions in the double transgenic animal model was analyzed by immunohistochemistry. BV2 cells were treated with gp120 protein and 7nAChR inhibitor, and the expressions of IL-1β and TNF- were detected using ELISA.@*RESULTS@#The results of PCR showed the bands of the expected size in F3 mice. Two F3 mice with successful double gene editing (7R/gp120) were obtained, and immunohistochemistry showed that the brain tissue of the mice did not express 7 nAChR but with high gp120 protein expression. In the cell experiment, treatment with gp120 promoted the secretion of IL-1β and TNF- in BV2 cells, while inhibition of 7nAChR significantly decreased the expression of IL-1β and TNF- ( < 0.001).@*CONCLUSIONS@#By mating gp120 Tg mice with 7R mice, we obtained gp120 transgenic mice with 7nAChR gene deletion, which serve as a new animal model for exploring the role of 7nAChR in gp120-induced neurotoxicity.


Subject(s)
Animals , Mice , Disease Models, Animal , Glycoproteins , Mice, Knockout , Mice, Transgenic , Tumor Necrosis Factor-alpha , alpha7 Nicotinic Acetylcholine Receptor , Metabolism
20.
Chinese Journal of Traumatology ; (6): 190-195, 2020.
Article in English | WPRIM | ID: wpr-827824

ABSTRACT

COVID-19 is known for its magical infectivity, fast transmission and high death toll based on the large number of infected people. From the perspective of the clinical manifestation, autopsy examination and pathophysiology, the essence of COVID-19 should be viewed as a sepsis induced by viral infection, and has the essential characteristics as sepsis induced by other pathogens. Therefore, in addition to etiological and supportive treatment, immunomodulatory therapy is also appropriate to severe COVID-19. Although there is still a lack of consensus on immunotherapy for sepsis so far, relatively rich experiences have been accumulated in the past decades, which will help us in the treatment of severe COVID-19. This article will elaborate immunotherapy of sepsis, though it may not be consistent.


Subject(s)
Humans , Adrenal Cortex Hormones , Therapeutic Uses , Betacoronavirus , Coronavirus Infections , Glycoproteins , Therapeutic Uses , Immunologic Factors , Therapeutic Uses , Pandemics , Pneumonia, Viral , Sepsis , Drug Therapy , Thymalfasin , Therapeutic Uses
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