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BACKGROUND: Presently, the global spread of COVID-19 is still going on, with more than 0.6 million new cases confirmed per day (as of November 20, 2021). However, since China entered a post-epidemic phase in mid-March 2020, the daily number of new domestic infections in the Chinese mainland has been maintained at almost zero or single digits, which was attributed to a series of effective measures for COVID-19 prevention and control adopted by the Chinese government. Among these measures, SARS-CoV-2 nucleic acid testing holds key role for the timely confirmation and isolation of the infections to prevent further transmission. METHODS: Referring to the national policy requirements, since April 30, 2020, The Affiliated Hospital of Qingdao University has conducted SARS-CoV-2 nucleic acid testing in its PCR laboratory for patients and social workers, as well as for environmental monitoring and employee screening. As of mid-November 2020, the daily amount of single-tube samples for nucleic acid testing rose above 4,000. RESULTS: In this article, a rapid and highly effective approach for SARS-CoV-2 nucleic acid daily testing is presented, allowing five technicians to complete nucleic acid testing in 6,500 single-tube samples in one day with a high level of quality. Using this approach, since the samples entered the PCR laboratory, all testing results were reported in 2.5-3 h with satisfactory quality control and precise reporting criterion as prerequisites. CONCLUSION: This testing approach provides a referable workflow for other testing institutions and is expected to play an important role in COVID-19 prevention and control.
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COVID-19 , Técnicas de Amplificação de Ácido Nucleico , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/prevenção & controle , China , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Técnicas de Amplificação de Ácido Nucleico/estatística & dados numéricos , Controle de Qualidade , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Fatores de TempoRESUMO
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.
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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
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.
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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
Heat shock protein 90 is induced in response to the cell stress. Its overexpression has been reported in many cancers with poor prognosis. It acts as a chaperone to the client proteins, especially the activated oncoproteins in malignancies to protect them from degradation. Heat shock protein 90 inhibition represented anti-cancer effects in many studies. Previous natural product-based compounds are limited by their association with target toxicities. BIIB021 is an orally available, fully synthetic novel small-molecule heat shock protein 90 inhibitor that has shown strong antitumor activities in a large number of preclinical models and is now under clinical investigation. This review will summarize its therapeutic effects and highlight the prospect of targeting heat shock protein 90 in the cancer therapy.
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Adenina/análogos & derivados , Antineoplásicos/uso terapêutico , Proteínas de Choque Térmico HSP90/genética , Neoplasias/tratamento farmacológico , Piridinas/uso terapêutico , Adenina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Humanos , Camundongos , Neoplasias/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Imatinib (IMA) is a common chemotherapy drug for the treatment of leukemia and can potentially lead to drug resistance and toxicity during the course of treatment. Monitoring IMA concentrations in body fluids is necessary to optimize therapeutic schedules and avoid overdosage. In this paper, a novel ultrasensitive electrochemical sensor based on CuMOF and SWCNTs@AuNPs was developed to determine this antileukemic drug. Herein, AuNPs were supported on carboxylic single-walled carbon nanotubes (SWCNT-COOH), and then poly(diallyldimethylammonium chloride) (PDDA) was used as a dispersant to overcome the internal van der Waals interactions among the CNTs, further increasing the AuNP loading. Moreover, the morphology, structure, composition, and electrochemical properties of the CuMOF-SWCNTs@AuNPs composite film were characterized using SEM, TEM, FT-IR, UV-vis, XRD, XPS, CV, and EIS. Due to the advantage of the superior electrocatalytic and conductive properties of SWCNTs@AuNPs and their preferable adsorptivity and affinity to IMA of CuMOF, the fabricated glassy carbon electrode significantly improved the determination performance via their synergetic amplified effect. Under optimal conditions, a wide linear response was exhibited in the range from 0.05 to 20.0 µM and the low detection limit of 5.2 nM. In addition, our prepared sensor has been applied to the analysis of IMA in blood serum samples with acceptable results. Therefore, our CuMOF-SWCNTs@AuNPs-based electrochemical sensor possessed prominent sensing responses for IMA, which could be used as a prospective approach in clinical application.
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Human epididymis protein 4 (HE4), a diagnostic biomarker of ovarian cancer, is crucial for monitoring the early stage of the disease. Hence, it is highly important to develop simple, inexpensive, and user-friendly biosensors for sensitive and quantitative HE4 assays. Herein, a new sandwich-type electrochemical immunosensor based on Prussian blue (PB) as a signal indicator and functionalized metal-organic framework nanocompositesas efficient signal amplifiers was fabricated for quantitative analysis of HE4. In principle, ketjen black (KB) and AuNPs modified on TiMOF (TiMOF-KB@AuNPs) could accelerate electron transfer on the electrode surface and act as a matrix for the immobilization of antibodies via cross-linking to improve the determination sensitivity. The PB that covalently binds to labeled antibodies endows the biosensors with intense electrochemical signals. Furthermore, the concentration of HE4 could be indirectly detected by monitoring the electroactivity of PB. Benefiting from the high signal amplification ability of the PB and MOF nanocomposites, this strategy displayed a wide linear range (0.1-80 ng mL-1) and a lower detection limit (0.02 ng mL-1). Hence, this study demonstrated great promise for application in clinical ovarian cancer diagnosis and treatment, and provided a new platform for detecting other cancer biomarkers.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Ferrocianetos , Ouro , Limite de Detecção , Estruturas Metalorgânicas , Neoplasias Ovarianas , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos , Técnicas Biossensoriais/métodos , Humanos , Estruturas Metalorgânicas/química , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Ferrocianetos/química , Técnicas Eletroquímicas/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/sangue , Feminino , Ouro/química , Nanopartículas Metálicas/química , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Imunoensaio/métodos , Anticorpos Imobilizados/química , Nanocompostos/químicaRESUMO
[This corrects the article DOI: 10.1021/acsomega.3c08002.].
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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.
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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
Imatinib (IMB), an anticancer drug, is extensively used for chemotherapy to improve the quality of life of cancer patients. The aim of therapeutic drug monitoring (TDM) is to guide and evaluate the medicinal therapy, and then optimize the clinical effect of individual dosing regimens. In this work, a highly sensitive and selective electrochemical sensor based on glassy carbon electrode (GCE) modified with acetylene black (AB) and a Cu (II) metal organic framework (CuMOF) was developed to measure the concentration of IMB. CuMOF with preferable adsorbability and AB with excellent electrical conductivity functioned cooperatively to enhance the analytical determination of IMB. The modified electrodes were characterized using X-rays diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared (FT-IR), ultraviolet and visible spectrophotometry (UV-vis), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), brunauerâemmettâteller (BET) and barrettâjoynerâhalenda (BJH) techniques. Analytical parameters such as the ratio of CuMOF to AB, dropping volumes, pH, scanning rate and accumulation time were investigated through cyclic voltammetry (CV). Under optimal conditions, the sensor exhibited an excellent electrocatalytic response for IMB detection, and two linear detection ranges were obatined of 2.5 nM-1.0 µM and 1.0-6.0 µM with a detection limit (DL) of 1.7 nM (S/N = 3). Finally, the good electroanalytical ability of CuMOF-AB/GCE sensor facilitated the successful determination of IMB in human serum samples. Due to its acceptable selectivity, repeatability and long-term stability, this sensor shows promising application prospects in the detection of IMB in clinical samples.
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Phosphogypsum (PG) is a solid waste produced from decomposition of phosphate rock in sulfuric acid. It can improve the physicochemical properties of soil. However, the application of PG will inevitably change the living environment of soil microorganisms and lead to the evolution of the soil microbial community. The effects of PG (0, 0.01%, 0.1%, 1%, 10% PG) on soil respiration, enzyme activity and microbial community were studied systematically by indoor incubation experiments. The results showed that the addition of 0.01% PG had little effect on the soil physicochemical properties and microflora. The soil respiration rate decreased with the increase of PG; The activities of catalase, urease and phosphatase were decreased and the activities of sucrase were increased by 10% PG treatment, while 0.01% or 0.1% PG treatment improve the urease activity; Soil microbial community response was significantly separated by amount of the PG amendment, and the application of 10% PG reduced the abundance, diversity and evenness of soil bacteria and fungi. Redundancy analysis (RDA) showed that soil bacterial composition was mainly driven by electrical conductivity (EC) and Ca2+, while fungal composition was mainly driven by F- and NH4+. In addition, the application of PG increased the abundance of salt-tolerant microorganisms and accelerated the degradation of soil organic matter. Overall, These results can help to revisit the current management of PG applications as soil amendments.
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Microbiota , Solo , Solo/química , Urease/metabolismo , Biomassa , Microbiologia do SoloRESUMO
A facile and sensitive electrochemical sensor for determining imatinib (IMA) was constructed by modifying a glassy carbon electrode (GCE) with a nanocarbon material, acetylene black (AB). The electrochemical behavior of IMA on the prepared GCE/AB was studied using electrochemical techniques, namely, differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy. The direct determination of IMA by the GCE/AB sensor was accomplished using DPV under optimized conditions. The method verification showed that the oxidation peak current was proportional to the concentrations of IMA in the linear ranges of 0.01-0.5 and 0.5-4 µM, with correlation coefficients of 0.9856 and 0.9946, respectively. The limit of detection of the GCE/AB sensor was 0.15 nM. Moreover, the GCE/AB sensor showed good precision and accuracy. Finally, the GCE/AB sensor was successfully applied to determine IMA in human serum samples, and the recoveries were satisfactory.
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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.
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Aterosclerose , Doença da Artéria Coronariana , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , gama-Glutamiltransferase , Fatores de Risco , BiomarcadoresRESUMO
PURPOSE: Although a number of genetic studies have attempted to link organic cation transporter 1/2 (OCTN1/2) polymorphisms to susceptibility of Crohn's disease (CD), the results were often inconsistent. The present study aimed at investigating the associations. METHODS: The PubMed, EBSCO, and BIOSIS databases were searched to identify eligible studies which were published in English before April 2011. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). RESULTS: A total of 15 case-control studies, containing 4,489 cases/5,351 controls for OCTN1 and 4,474 cases/5,377 controls for OCTN2 were included. Overall, significant associations were found between OCTN1/2 polymorphisms and susceptibility of Crohn's disease for all genetic models. In the subgroup analyses, significant associations were found in the Caucasian population for OCTN1 (TT vs. CC: OR = 1.425, 95% CI 1.247-1.628; TT vs. CT: OR = 1.299, 95% CI 1.149-1.468; dominant model: OR = 1.344, 95% CI 1.197-1.508; and recessive model: OR = 1.179, 95% CI 1.066-1.305) and for OCTN2 (CC vs. GG: OR = 1.309, 95% CI 1.078-1.588; CC vs. CG: OR = 1.200, 95% CI 1.002-1.438; dominant model (OR = 1.231, 95% CI 1.036-1.462; recessive model: OR = 1.148, 95% CI 1.031-1.279). Significant associations were not found in the East Asian population. CONCLUSIONS: This meta-analysis suggests that OCTN1/2 polymorphisms were associated with susceptibility of CD in the Caucasian population but not in the East Asian population.
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Doença de Crohn/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Proteínas de Transporte de Cátions Orgânicos/genética , Polimorfismo de Nucleotídeo Único/genética , Intervalos de Confiança , Frequência do Gene/genética , Humanos , Razão de Chances , Membro 5 da Família 22 de Carreadores de Soluto , SimportadoresRESUMO
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.
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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
BACKGROUND: The single nucleotide polymorphisms (SNPs) of Interleukin-10 (IL-10) gene have been linked with the risk of oral carcinoma (OC) in a relatively small sample size. Our study aims to investigate the pooled associations by conducting a meta-analysis of published studies. METHODS: PubMed, Web of Science and Google Scholar databases were searched to identify eligible studies published in English before October 2019. The odds ratio (OR) with a 95% confidence interval (CI) was used to assess association. The publication bias was detected by Begg's test. Sensitivity and cumulative analyses were performed to evaluate the stability of crude results. RESULTS: The meta-analysis involved eight studies. Significant associations were certified between IL-10 gene -1082A/G polymorphism and susceptibility of OC for A vs. G (OR=1.817, 95% CI: 1.481-2.230), AA vs. GG (OR=3.436, 95% CI: 2.281-5.175), dominant genetic model (OR=2.913, 95% CI: 1.939-4.376), and recessive genetic model (OR=1.886, 95% CI: 1.372-2.594) in overall population, East Asians and South Asians. In addition, the significant association between -592A/C polymorphism of the gene and susceptibility of OC were detected in South Asians. CONCLUSIONS: The meta-analysis results support that the IL-10 gene -1082G allele is a risk factor for OC in East Asians and South Asians, and IL-10 gene -592C allele is a protective factor for the disease.
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Interleucina-10/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Predisposição Genética para Doença , Humanos , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
The final goal for treatment of congenital heart diseases (CHD) is to resume not only the normal heart structure but also physiology. The present study evaluates surgical results at molecular basis on the proteomic pattern in the pre- and post-operative period in tetralogy of Fallot (TOF) and ventricular septal defect (VSD) in order to find whether structure repair is associated with clinically important molecular changes in CHD. Differential protein analysis by using two-dimensional gel electrophoresis and mass spectrometry followed by ELISA validation was performed in the plasma samples of patients with TOF (n=82) or VSD (n=82) preoperatively, 6-month postoperatively, and in normal controls (n=82). A total of 473 protein spots in preoperative patients and 515 in postoperative patients were detected. Significantly (P<0.01) downregulated or upregulated proteins were detected. Validation of proteins in the new cohort of patients demonstrated that in VSD patients, postoperative complement component C3c (P<0.05) was partially and serum amyloid P-component (P<0.05) was completely recovered. In TOF patients, postoperative gelsolin (P<0.05) was partially recovered. In contrast, the elevated fibrinogen gamma chain level (P<0.01) in preoperative patients became normal postoperatively (P=0.1 vs. control). Thus, we have for the first time by using proteomic methods demonstrated that repair surgery for CHD not only corrects the structure malformation but also resumes the normality of certain altered proteins at molecular level. Identification of the recovered or unchanged proteins may facilitate the evaluation of the surgical results and the personalized management in postoperative period and long-term.
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BACKGROUND: Genome-wide linkage analysis revealed the polymorphism of rs6748040 and glutamic acid repeat are potential pathogenic factors of early-onset myocardial infarction (MI). The present study was designed to investigate the associations of Alström syndrome 1 (ALMS 1) gene in Chinese populations with early-onset coronary artery disease (CAD). METHODS: The two variants of the ALMS 1 gene were genotyped in 1252 early-onset CAD patients and 1378 controls using PCR, followed by Sml I restriction enzyme digestion or direct sequencing of the PCR product. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: A significant association between the ALMS 1 G/A variant and the risk of early-onset MI was detected in G vs.A (OR = 1.371, 95% CI: 1.183-1.589), GG vs. AA (OR = 2.037, 95% CI: 1.408-2.948), dominant genetic model (OR = 1.794, 95% CI: 1.254-2.567), and recessive genetic model (OR = 1.421, 95% CI: 1.177-1.716). 14 glutamic acid repeat (A14) is risk factor for early-onset MI (OR = 1.605, 95% CI: 1.313-1.962) and 17 glutamic acid repeat (A17) is protective factor for the disease (OR = 0.684, 95% CI: 0.601-0.827). These associations were not detected in early-onset CAD patients. CONCLUSIONS: Our findings indicated that G/A variant (rs6748040) and glutamic acid repeat polymorphism of the ALMS 1 gene associated with the risk of early-onset MI in the Chinese population.
Assuntos
Proteínas de Ciclo Celular/genética , Doença da Artéria Coronariana/genética , Adulto , Idade de Início , Povo Asiático/genética , Estudos de Casos e Controles , Éxons , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.