RESUMO
In this work, novel selective recognition materials, namely magnetic molecularly imprinted polymers (MMIPs), were prepared. The recognition materials were used as pretreatment materials for magnetic molecularly imprinted solid-phase extraction (MSPE) to achieve the efficient adsorption, selective recognition, and rapid magnetic separation of methotrexate (MTX) in the patients' plasma. This method was combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) to achieve accurate and rapid detection of the plasma MTX concentration, providing a new method for the clinical detection and monitoring of the MTX concentration. The MMIPs for the selective adsorption of MTX were prepared by the sol-gel method. The materials were characterized by transmission electron microscopy, Fourier transform-infrared spectrometry, X-ray diffractometry, and X-ray photoelectron spectrometry. The MTX adsorption properties of the MMIPs were evaluated using static, dynamic, and selective adsorption experiments. On this basis, the extraction conditions were optimized systematically. The adsorption capacity of MMIPs for MTX was 39.56 mgg-1, the imprinting factor was 9.40, and the adsorption equilibrium time was 60 min. The optimal extraction conditions were as follows: the amount of MMIP was 100 mg, the loading time was 120 min, the leachate was 8:2 (v/v) water-methanol, the eluent was 4:1 (v/v) methanol-acetic acid, and the elution time was 60 min. MTX was linear in the range of 0.00005-0.25 mg mL-1, and the detection limit was 12.51 ng mL-1. The accuracy of the MSPE-HPLC-UV method for MTX detection was excellent, and the result was consistent with that of a drug concentration analyzer.
Assuntos
Impressão Molecular , Adsorção , Cromatografia Líquida de Alta Pressão , Humanos , Fenômenos Magnéticos , Metanol , Metotrexato , Impressão Molecular/métodos , Polímeros Molecularmente Impressos , Polímeros/química , Extração em Fase Sólida/métodos , ÁguaRESUMO
Transforming growth factor beta (TGF-ß) plays key roles in regulating cellular proliferation and maintaining tissue homeostasis. TGF-ß exerts tumor-suppressive effects in the early stages of carcinogenesis, but it also plays tumor-promoting roles in established tumors. Additionally, it plays a critical role in cancer radiotherapy. TGF-ß expression or activation increases in irradiated tissues, and studies have shown that TGF-ß plays dual roles in cancer radiosensitivity and is involved in ionizing radiation-induced fibrosis in different tumor microenvironments (TMEs). Furthermore, TGF-ß promotes radioresistance by inducing the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs), suppresses the immune system and facilitates cancer resistance. In particular, the links between TGF-ß and the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) axis play a critical role in cancer therapeutic resistance. Growing evidence has shown that TGF-ß acts as a radiation protection agent, leading to heightened interest in using TGF-ß as a therapeutic target. The future of anti-TGF-ß signaling therapy for numerous diseases appears bright, and the outlook for the use of TGF-ß inhibitors in cancer radiotherapy as TME-targeting agents is promising.
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Neoplasias/metabolismo , Neoplasias/radioterapia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fibrose , Humanos , Modelos Biológicos , Neoplasias/imunologia , Neoplasias/patologiaRESUMO
BACKGROUND: Deficiency of protein C (PC) affects the balance between blood coagulation and fibrinolysis in the human body. Chromogenic-based assay is recommended as the preferred screening method for detecting PC deficiency. We established a PC detection system based on the chromogenic substrate assay. METHODS: First, a kit for the determination of PC activity in plasma was elaborately developed and its reaction parameters on XL-3200c were explored. Then, we evaluated its performance and collected specimens to compare the test results obtained with those of the Siemens detection system. Finally, the clinical diagnostic efficacy of this detection system for deep vein thrombosis (DVT) was assessed. RESULTS: Optimum conditions for PC detection were 0.25-0.1 U/ml protein C activator Protac® and 2.5-1 mM Pefachrome® PCa5297. The composition and concentration ranges of buffer substances and stabilizers in the kit were also explored. Satisfactory results were observed in performance evaluation. The test results of the newly built detection system were highly correlated with those of the Siemens detection system (R2 = 0.9771 in the control group and R2 = 0.9776 in the DVT group), and Bland-Altman plots also showed high consistency between the two detection systems. In addition, the area under the curve (AUC) of the newly built PC detection system for DVT was 0.888, indicating this system could effectively improve the diagnostic sensitivity and specificity for DVT. CONCLUSION: In this study, a sensitive, wide linear range and reliable PC activity detection system were established.
Assuntos
Análise Química do Sangue/métodos , Proteína C/análise , Trombose Venosa/sangue , Biomarcadores/sangue , Análise Química do Sangue/instrumentação , Análise Química do Sangue/normas , Humanos , Sensibilidade e Especificidade , Trombose Venosa/diagnósticoRESUMO
The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120-1.892), dominant genetic model (OR 1.266, 95% CI 1.027-1.546), and recessive genetic model (OR 1.306, 95% CI 1.040-1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 µmol/L), least abundant in CC genotype (11.37 ± 5.23 µmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 µmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135-1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population.
Assuntos
Doença da Artéria Coronariana , Predisposição Genética para Doença , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de RiscoRESUMO
BACKGROUND: Mounting evidence from recent studies has revealed the association of lncRNA PANDAR expression levels with outcomes in several types of cancer. However, inconsistent results have also been reported, which rationalized a meta-analysis of available data to analyze the prognostic value of lncRNA PANDAR. METHODS: From inception to May 26, 2018, electronic literature databases including PubMed (medline), the Cochrane Library, ScienceDirect, Springer, ISI Web of Knowledge, Wiley Online library, BioMed Central, and Embase were searched for literature collections. The hazard ratios (HR) with 95% confidence interval (95% CI) were utilized to calculate pooled effect size. RESULTS: A total of 1,132 cancer patients were enrolled in the present meta-analysis to assess the prognostic value of PANDAR in various carcinomas. Promoted PANDAR expression was demonstrated to significantly predict unfavorable OS (HR = 1.77, 95% CI: 1.12 - 2.80, p = 0.014) by the random effects model. According to the stratified analyses and meta-regression results, the heterogeneity of present analysis may be attributed to the differences of cancer resources. Furthermore, over-expression of PANDAR was revealed to be effectively predictive of cancer progression (HR = 1.70, 95% CI: 1.41 - 2.05, p < 0.00001) and LNM (HR = 1.71, 95% CI: 1.39 - 2.10, p < 0.00001). CONCLUSIONS: The present findings indicate that increased PANDAR is associated with poor OS in patients with general carcinomas and may serve as a useful clinical prognostic biomarker.
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Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , RNA Longo não Codificante/genética , Humanos , Metástase Linfática , Neoplasias/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
AIMS: Growing evidence from recent studies has shown that lncRNA HULC plays a role in the development of multiple carcinomas. This meta-analysis aimed to analyze available data to identify the prognostic value of HULC in multiple tumors. METHODS: A systematic search was performed by using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) computerized databases from inception to Nov 30, 2016. The quality of the publications was assessed according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE and PRISMA. Pooled hazard ratios (HR) with 95% confidence interval (95% CI) were calculated to summarize the effect. RESULTS: A total of ten studies with 1077 cancer patients were pooled in the present meta-analysis to evaluate the prognostic value of HULC in multiple tumors. High expression levels of HULC were demonstrated to be associated with poor overall survival (OS) (HR=2.44, 95%CI: 1.96-3.03, P=0.000). Subgroup analysis showed that cancer type (digestive or non-digestive disease), residence region (China), sample size (more or less than 100) and follow-up months (more or less than 60) did not alter the predictive value of HULC on OS in various cancers. Additionally, increased HULC expression was found to be moderately associated with tumor stage and progression (III/IV vs. I/II: HR=1.59, 95% CI: 1.31-1.92, P<0.00001). Furthermore, elevated HULC expression significantly predicted distant metastasis (HR=3.90, 95% CI: 1.89-8.02, P=0.0002) and lymph node metastasis (HR=2.04, 95% CI: 1.03-4.05, P=0.04) respectively. No significant heterogeneity was observed among studies except lymph node metastasis. CONCLUSION: The results indicate that HULC expression level is an independent prognostic biomarker for unfavorable OS and metastasis in general tumors.
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Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Neoplasias/mortalidade , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Intervalo Livre de Doença , Humanos , Taxa de SobrevidaRESUMO
The protein tyrosine phosphatase N22 (PTPN22) gene C1858T polymorphism has been reported to be associated with susceptibility to type 1 diabetes (T1D) in relatively small sample sizes. This study aimed at investigating the pooled association by carrying out a meta-analysis on the published studies. The Medline, EBSCO, and BIOSIS databases were searched to identify eligible studies published in English before June 2012. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). The presence of heterogeneity and publication bias was explored by using meta-regression analysis and Begg's test, respectively. A total of 28 studies were involved in this meta-analysis. Across all populations, significant associations were found between the PTPN22 C1858T polymorphism and susceptibility to T1D under genotypic (TT vs. CC [OR = 3.656, 95% CI: 3.139-4.257], CT vs. CC [OR = 1.968, 95% CI: 1.683-2.300]), recessive (OR = 3.147, 95% CI: 2.704-3.663), and dominant models (OR = 1.957, 95% CI: 1.817-2.108). In ethnicity- and sex-stratified analyses, similar associations were found among Caucasians and within Caucasian male and female strata. The meta-analysis results suggest that the PTPN22 C1858T polymorphism was associated with susceptibility to T1D among the Caucasian population, and males who carried the -1858T allele were more susceptible to T1D than females.
Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Estudos de Casos e Controles , Intervalos de Confiança , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Geografia , Heterozigoto , Humanos , Masculino , Razão de Chances , Prevalência , Viés de Publicação , Análise de Regressão , Sensibilidade e Especificidade , Fatores Sexuais , População Branca/genéticaRESUMO
Background: Thrombosis and inflammation are crucial elements in the pathogenesis of cardiovascular disease. Hematological parameters elucidate information involving the inflammatory and blood coagulation processes. Objectives: The current study explored the association of hematological parameters with EOCAD to identify specific risk factors. Design: A single-center retrospective case-control study was conducted with 1693 coronary artery disease patients and 1693 controls. Methods: Hematological parameters were examined through an automated analyzer. Results: The basophil percentage was significantly reduced in EOCAD (0.43 ± 0.26, p < 0.001) and MI (0.33 ± 0.24, p < 0.001) groups compared with controls (0.54 ± 0.28). The eosinophil percentage was also significantly lower in EOCAD (2.21 ± 1.71, p < 0.001) and MI (1.71 ± 2.44, p < 0.001) groups compared with controls (2.41 ± 1.75). The lymphocyte percentage in patients of EOCAD and MI and controls was 31.65 ± 7.93, 25.48 ± 9.43, and 34.82 ± 7.28, respectively. A significant difference was observed among the groups (p < 0.001). Except for the mean corpuscular hemoglobin (MCH), other red blood cell (RBC) parameters significantly differed between EOCAD patients and controls. The red blood cell distribution width (RDW), hematocrit (HCT), RBC count, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and hemoglobin level were associated with EOCAD prevalence after adjusting for baseline differences. Platelet volume distribution width (PDW) also correlated with EOCAD prevalence (ORadjust = 1.087, 95% CI: 1.044-1.131). Conclusions: Hematological parameters are closely associated with EOCAD. Moreover, leukocyte parameters correlated with the presence and severity of the disease. In addition, erythrocyte parameters were associated with the disease presence but not with the disease severity. Among the platelet parameters, only PDW was related to the disease presence.
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BACKGROUND: Serum gamma-glutamyltransferase (GGT) activity has been proposed as a promising predictor of atherosclerosis-related complications and a prognostic marker for cardiovascular diseases. The objective of this study was to investigate the potential correlation between serum levels of GGT and early-onset coronary artery disease (EOCAD). METHODS: A retrospective, hospital-based case-control study was conducted, which included 860 patients with EOCAD and gender- and age-matched controls. Serum levels of GGT were measured using the reference measurement procedure on an automatic biochemistry analyser. RESULTS: The serum GGT levels of patients with EOCAD (34.90 ± 31.44 U/L) were significantly higher than those of the control group (21.57 ± 16.44 U/L, p < .001). Elevated serum levels of GGT were found to be an independent risk factor for EOCAD, with an odds ratio (OR) of 1.021 (95% confidence interval (CI): 1.014-1.029). Additionally, for every quartile increase in serum GGT levels, the risk of developing EOCAD increased by 1.6-fold. Moreover, serum GGT levels were significantly associated with disease severity, with lower GGT levels observed in patients without significant vascular disease (31.74 ± 24.06 U/L) compared to those with two-vessel disease (33.06 ± 25.00 U/L, p = .002) and three-vessel disease (37.75 ± 36.76 U/L, p = .001). CONCLUSIONS: The results of this study suggest that elevated serum GGT levels are associated with the development of EOCAD, and GGT may be implicated in the pathogenesis of the disease. Further large-scale prospective studies are needed to explore the potential relationship between serum GGT levels and the dynamic development of EOCAD.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , gama-Glutamiltransferase , Fatores de Risco , BiomarcadoresRESUMO
Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Moreover, study has reported that the upregulation of PD-L1 and apurinic/apyrimidinic endonuclase 1 (APE1) are associated with tumorigenesis and poor prognosis of gastric cancer. In the present study, the number of CD3+ T lymphocytes and the expressions of PD-1 and PD-L1 in LSCC and HSCC were detected in clinical samples. In addition, the expressions of PD-L1 and APE1 and their correlation were explored. The results showed that PD-1+ T lymphocytes were wildly infiltrated and PD-L1 was overexpressed in LSCC and HSCC tissues. PD-1 had a positive correlation with cancer progression, and glottic and subglottic LSCC tissues might have a more active immune microenvironment. Moreover, the results showed that upregulated co-expression of PD-L1 and APE1 was a biomarker of LSCC, and APE1 could regulate the expression of PD-L1 through NF-κB signaling pathway. In conclusion, the combine detection of the expressions of PD-1, PD-L1 and APE1 will provide predictive value for the treatment of LSCC and HSCC via immune checkpoint inhibitors, which will help us to identify the patient population more likely to benefit from the immune checkpoint inhibitors based on the tumor immune microenvironment.
Assuntos
Antígeno B7-H1/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Neoplasias Hipofaríngeas/imunologia , Neoplasias Laríngeas/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Quimioterapia Adjuvante/métodos , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/terapia , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/terapia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologiaRESUMO
BACKGROUND: Fatty acids (FAs) play crucial roles in modulating and preventing diseases in humans, including early-onset coronary artery disease (EOCAD). In this study, we aimed to provide a profile of FAs in the serum of EOCAD patients and identify potential EOCAD-associated FAs. METHODS: In the first stage, we analyzed the FAs profiles in pooled samples of patients with EOCAD using gas chromatography-mass spectrometry. In the second stage, the serum levels of the candidate FAs were validated in EOCAD patients. RESULTS: A total of 128 EOCAD patients and 64 controls were included in the study. Forty-nine serum FAs were quantified in pooled samples; three ω-3 FAs were identified to be associated with EOCAD. Moreover, results from the validation stage indicated that serum levels of docosahexaenoic acid (DHA) were significantly lower in EOCAD patients (55.43 ± 33.86 µg/ml) and myocardial infarction (MI) patients (47.49 ± 28.44 µg/ml) than those in the controls (70.65 ± 43.56 µg/ml). Multivariate regression analysis revealed that elevated serum DHA level was an independent protective factor for EOCAD [odds ratio (OR) = 0.8917, 95% confidence interval (CI): 0.879-0.957] and MI (OR = 0.835, 95% CI: 0.799-0.862). Decreased serum levels of docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) were observed in the early-onset MI group. CONCLUSION: The study provided the serum FAs profile of EOCAD and confirmed that the decrease in serum levels of DHA, DPA, and EPA was associated with EOCAD. These findings might contribute to understanding the cardiovascular effects of FAs, particularly the protective effects of ω-3 polyunsaturated FAs.
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BACKGROUND: Amino acids play essential roles in protein construction and metabolism. Our study aims to provide a profile of amino acid changes in the serum of patients with early-onset coronary artery disease (EOCAD) and identify potential disease biomarkers. METHODS: Ultra-performance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry (UPLC-MRM-MS/MS) was used to determine the amino acid profile of patients with EOCAD in sample pools. In the validation stage, the serum levels of candidate amino acids of interest are determined for each sample. RESULTS: A total of 128 EOCAD patients and 64 healthy controls were included in the study. Eight serum amino acids associated with disease state were identified. Compared with the control group, serum levels of seven amino acids (L-Arginine, L-Methionine, L-Tyrosine, L-Serine, L-Aspartic acid, L-Phenylalanine, and L-Glutamic acid) increased and one (4-Hydroxyproline) decreased in the patient group. Results from the validation stage demonstrate that serum levels of 4-Hydroxyproline were significantly lower in myocardial infarction (MI) patients (9.889 ± 3.635 µg/mL) than those in the controls (16.433 ± 4.562 µmol/L, p < 0.001). Elevated serum 4-Hydroxyproline levels were shown to be an independent protective factor for MI (OR = 0.863, 95% CI: 0.822-0.901). The significant negative correlation was seen between serum 4-Hydroxyproline levels and cardiac troponin I (r = -0.667) in MI patients. CONCLUSION: We have provided a serum amino acid profile for EOCAD patients and screened eight disease state-related amino acids, and we have also shown that 4-Hydroxyproline is a promising target for further biomarker studies in early-onset MI.
Assuntos
Aminoácidos/sangue , Doença da Artéria Coronariana/sangue , Fatores de Risco de Doenças Cardíacas , Adulto , Idade de Início , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Medição de Risco , Espectrometria de Massas em Tandem/métodosRESUMO
Runt-related transcription factors regulate many developmental processes such as proliferation and differentiation. In this study, the function of the runt-related transcription factor 1 (RUNX1) was investigated in head and neck squamous cell carcinoma (HNSCC). Our results show that RUNX1 expression was elevated in HNSCC patients, which was greatly correlated with the N stage, tumor size, and American Joint Committee on Cancer stage. Cox proportional hazard models showed that RUNX1 could be used as a prognostic indicator for the overall survival of HNSCC patients (hazard ratio, 5.572; 95% confidence interval, 1.860-9.963; P < 0.001). Moreover, suppression of RUNX1 inhibited HNSCC cell proliferation, migration, and invasion. Using the HNSCC xenograft nude mouse model, we found that the shRUNX1-transfected tumor (sh-RUNX1) was significantly smaller both in size and weight than the control vector-transfected tumor (sh-Control). In conclusion, our results show that the elevated RUNX1 expression was correlated with tumor growth and metastasis in HNSCC, indicating that RUNX1 could be used as a biomarker for tumor recurrence and prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Animais , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Interleukin-18 (IL-18) belongs to the IL-1 family and is an essential proinflammatory and immune regulatory cytokine. The present study was designed to investigate the expression and function of IL-18 in colon cancer. In clinical analyses, mRNA and protein expressions of IL-18 were decreased in tissues of colon cancer patients. This decreased expression of IL-18 was significantly correlated with the tumor size (P = 0.001) and American Joint Committee on Cancer (AJCC) stage (P = 0.013). Patients with IL-18-positive tumors had a better survival rate than patients with IL-18-negative tumors. Moreover, upregulation of IL-18 inhibited colon cancer cell proliferation. Our data suggest that the decreased expression of IL-18 in colon cancer was associated with prognosis and tumor proliferation. IL-18 may be considered a novel tumor suppressor and a potential therapeutic target for colon cancer patients.
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Neoplasias do Colo/patologia , Regulação para Baixo , Interleucina-18/genética , Interleucina-18/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/mortalidade , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Estadiamento de Neoplasias , Análise de Sobrevida , Carga TumoralRESUMO
PURPOSE: The present study aims to discover novel serum biomarkers of early-onset myocardial infarction (MI) using proteomic analysis. EXPERIMENTAL DESIGN: In the first stage, the iTRAQ-coupled LC-MS/MS technique is utilized to investigate protein profiles of patients with early-onset MI. In the second stage, these candidate proteins are validated using ELISA. RESULTS: A total of 538 proteins are quantified, with pregnancy zone protein (PZP), leucine-rich α-2-glycoprotein (LRG) and Apolipoprotein C-I (Apo C-I) being upregulated and Apolipoprotein A-I (Apo A-I) and Apolipoprotein A-IV (Apo A-IV) downregulated in early-onset MI patients. Results from the validation stage demonstrate that the serum concentrations of PZP and LRG are significantly increased in the early-onset MI group. The correlation between the concentrations of C-reactive protein (CRP) and the two candidate biomarkers is positive. Area under the curve values used to diagnose early-onset MI for LRG and PZP are 0.939 and 0.874, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Five differential serum proteins are identified in early-onset MI using proteomic analysis. Lipoprotein-related biomarkers further demonstrate the close relationship between lipid metabolism and the disease. Inflammation-associated LRG and PZP may be novel biomarkers of the disease. In addition, changes in these proteins may partly reveal the possible mechanisms in the pathogenesis and pathophysiology of early-onset MI.
Assuntos
Glicoproteínas/sangue , Infarto do Miocárdio/sangue , Proteínas da Gravidez/sangue , Proteômica , Adulto , Idade de Início , Biomarcadores/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Curva ROCRESUMO
BACKGROUND: Adenosine deaminase (ADA) regulates purine metabolism through the conversion of adenosine to uric acid (UA). Adenosine and UA are closely associated with cardiovascular events, but the correlation between serum ADA activity and coronary artery disease (CAD) has not been defined. METHODS: We performed a hospital-based retrospective case-control study that included a total of 5212 patients with CAD and 4717 sex- and age-matched controls. The serum activity of ADA was determined by peroxidase assays in an automatic biochemistry analyzer. RESULTS: Serum ADA activity in the CAD group (10.08 ± 3.57 U/l) was significantly lower than that of the control group (11.71 ± 4.20 U/l, p < 0.001). After adjusting for conventional factors, serum ADA activity negatively correlated with the presence of CAD (odds ratio = 0.852, 95% confidence interval: 0.839-0.865, p < 0.001). Among the patients with CAD, serum ADA activity was lowest in patients with myocardial infarction (MI; 9.77 ± 3.80 U/l). Diabetes mellitus and hypertension increased the serum ADA activity in CAD patients. CONCLUSIONS: Serum ADA activity is significantly attenuated in patients with CAD, particularly in MI. We propose a mechanism by which the body maintains adenosine levels to protect the cardiovascular system in the event of CAD.
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AIM: There is increasing evidence that high expression levels of the gastric carcinoma highly expressed transcript 1 (GHET1), a long noncoding RNA (lncRNA), are associated with cancer prognosis and may be used as a valuable biomarker for cancer patients. The purpose of this meta-analysis was to analyze existing data to reveal potential clinical applications of GHET1 for cancer prognosis and tumor progression. All of these studies included in this meta-analysis were collected through a variety of retrieval strategies; and the enrolled articles were qualified via the meta-analysis of enrolled studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklists. MATERIALS AND METHODS: The literature collection was performed by a comprehensive search through electronic databases for studies published on or before March 10, 2019. These included the Cochrane library, PubMed, Embase, Web of Science, Springer, Science Direct, and three Chinese databases: CNKI, Weipu, and Wanfang. Seven studies that met the specified criteria were analyzed in the present research. RESULTS: The combined results indicate that an elevated GHET1 expression level is significantly associated with poor overall survival (OS) (HR = 2.40, 95% CI: 1.87-3.08, p < 0.001) and tumor progression (III/IV vs. I/II: HR = 1.80, 95% CI: 1.48-2.18, p < 0.001) in multiple cancers. The elevated GHET1 expression was also associated with lymph node metastasis (LNM) (HR = 2.44, 95% CI: 1.86-3.20, p < 0.001) in Chinese cancer patients. Conclusions. The present findings indicate that an increased GHET1 expression level is associated with poor OS, tumor progression, and LNM in patients with multiple tumors and may serve as a useful prognostic biomarker in Chinese cancer patients.
Assuntos
Neoplasias/genética , Neoplasias/mortalidade , RNA Longo não Codificante/genética , Regulação para Cima , Biomarcadores Tumorais , China , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Prognóstico , Análise de SobrevidaRESUMO
Acute and subacute toxicity of the nonylphenol (NP) on fish was investigated in laboratory toxicity tests with rosy barb (Puntius conchonious). The acute toxicity of NP to rosy barb was determined in semi-static bioassays. Median lethal concentration (LC50) for 96 h was 1.72 microM. The effects of sublethal concentrations of NP (0.17, 0.34 and 0.68 microM) on the structures and biochemical parameters [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanin aminotransferase (ALT)] in gills, liver and kidney of rosy barb were studied after 14 days. The results showed that NP caused alteration of the structure in organs, as evidenced by the hyperplasia of epithelium and the fusion of secondary lamellae in the gills, the disappearance of the cell membrane and the cell necrosis in the liver as well as haemorrhages in the kidney. In addition, the functional enzyme activities were also changed. The increase trend in ALP activity in organs of fish treated with NP was recorded. The levels of AST and ALT in gills, liver and kidney were stimulated to rise at the lower concentration and fall at the higher concentration NP treatment compared to controls. This study suggests that NP can alter of the structures and biochemical parameters within non-endocrine tissue of fish and these changes may be mediated via destroying membrane structure and inducing cell necrosis.
Assuntos
Cyprinidae/metabolismo , Fenóis/toxicidade , Testes de Toxicidade Aguda , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Brânquias/patologia , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologiaRESUMO
Serum uric acid (UA) is the final product of purine metabolism in humans. The present study is aimed at identifying the potential association between serum UA and early-onset coronary artery disease (EOCAD). The study population consisted of 1093 EOCAD patients aged ≤50 years, and 1117 age- and sex-matched apparently healthy people served as controls. The concentrations of UA were measured by uricase method. The severity of CAD was evaluated by Gensini score. The mean serum level of UA was 5.843 ± 1.479 mg/dl in EOCAD patients and 5.433 ± 1.529 mg/dl in controls. Serum UA levels were significantly higher in the EOCAD group than those in the control group (P < 0.001) and was an independent risk factor for EOCAD (OR = 1.100, 95% CI: 1.022-1.185). The early-onset myocardial infarction patients with 3-vessel disease had higher serum UA levels than those with 1- or 2-vessel disease. The serum UA levels of EOCAD patients with acute coronary syndrome were significantly higher than those with chronic coronary artery disease. EOCAD patients with hyperuricemia had higher Gensini scores than those without hyperuricemia. In addition, the serum UA levels were affected by drinking (P < 0.01) and were positively correlated with serum creatinine (r = 0.323) and weight (r = 0.327). Our results show that serum UA was an independent risk factor for EOCAD. The serum UA levels were associated with the presence and severity of EOCAD and suggested that UA may be involved in the progression of EOCAD.