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BACKGROUND: Cardiovascular magnetic resonance (CMR) has demonstrated excellent performance in the diagnosis of cardiac amyloidosis (CA). However, misdiagnosis occasionally occurs because the morphological and functional features of CA are non-specific. This study was performed to determine the value of non-contrast CMR T1ρ in the diagnosis of CA. METHODS: This prospective study included 45 patients with CA, 30 patients with hypertrophic cardiomyopathy (HCM), and 10 healthy controls (HCs). All participants underwent cine (whole heart), T1ρ mapping, pre- and post-contrast T1 mapping imaging (three slices), and late gadolinium enhancement using a 3T whole-body MRI system. All participants underwent T1ρ at two spin-locking frequencies: 0Hz and 298Hz. ECV maps were obtained using pre- and post-contrast T1 maps. The myocardial T1ρ dispersion map, termed myocardial dispersion index (MDI), was also calculated. All parameters were measured in the left ventricular myocardial wall. Participants in the HC group were scanned twice on different days to assess the reproducibility of T1ρ measurements. RESULTS: Excellent reproducibility was observed upon evaluation of the coefficient of variation between two scans (T1ρ [298Hz]: 3.1%; T1ρ [0Hz], 2.5%). The ECV (HC: 27.4 ± 2.8% vs. HCM: 32.6 ± 5.8% vs. CA: 46 ± 8.9%; p < 0.0001), T1ρ [0Hz] (HC: 35.8 ± 1.7 ms vs. HCM: 40.0 ± 4.5 ms vs. CA: 51.4 ± 4.4 ms; p < 0.0001) and T1ρ [298Hz] (HC: 41.9 ± 1.6 ms vs. HCM: 48.8 ± 6.2 ms vs. CA: 54.4 ± 5.2 ms; p < 0.0001) progressively increased from the HC group to the HCM group, and then the CA group. The MDI progressively decreased from the HCM group to the HC group, and then the CA group (HCM: 8.8 ± 2.8 ms vs. HC: 6.1 ± 0.9 ms vs. CA: 3.4 ± 2.1 ms; p < 0.0001). For differential diagnosis, the combination of MDI and T1ρ [298Hz] showed the greatest sensitivity (98.3%) and specificity (95.5%) between CA and HCM, compared with the native T1 and ECV. CONCLUSIONS: The T1ρ and MDI approaches can be used as non-contrast CMR imaging biomarkers to improve the differential diagnosis of patients with CA.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly cancer with no clinically ideal biomarkers for early diagnosis. The objective of this study was to develop and validate a user-friendly diagnostic tool for early ESCC detection. METHODS: The study encompassed three phases: discovery, verification, and validation, comprising a total of 1309 individuals. Serum autoantibodies were profiled using the HuProtTM human proteome microarray, and autoantibody levels were measured using the enzyme-linked immunosorbent assay (ELISA). Twelve machine learning algorithms were employed to construct diagnostic models, and evaluated using the area under the receiver operating characteristic curve (AUC). The model application was facilitated through R Shiny, providing a graphical interface. RESULTS: Thirteen autoantibodies targeting TAAs (CAST, FAM131A, GABPA, HDAC1, HDGFL1, HSF1, ISM2, PTMS, RNF219, SMARCE1, SNAP25, SRPK2, and ZPR1) were identified in the discovery phase. Subsequent verification and validation phases identified five TAAbs (anti-CAST, anti-HDAC1, anti-HSF1, anti-PTMS, and anti-ZPR1) that exhibited significant differences between ESCC and control subjects (P < 0.05). The support vector machine (SVM) model demonstrated robust performance, with AUCs of 0.86 (95% CI: 0.82-0.89) in the training set and 0.83 (95% CI: 0.78-0.88) in the test set. For early-stage ESCC, the SVM model achieved AUCs of 0.83 (95% CI: 0.79-0.88) in the training set and 0.83 (95% CI: 0.77-0.90) in the test set. Notably, promising results were observed for high-grade intraepithelial neoplasia, with an AUC of 0.87 (95% CI: 0.77-0.98). The web-based implementation of the early ESCC diagnostic tool is publicly accessible at https://litdong.shinyapps.io/ESCCPred/ . CONCLUSION: This study provides a promising and easy-to-use diagnostic prediction model for early ESCC detection. It holds promise for improving early detection strategies and has potential implications for public health.
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Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.
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Autoanticorpos , Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Survivina , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/genética , Masculino , Feminino , Pessoa de Meia-Idade , Survivina/genética , Survivina/imunologia , alfa-Fetoproteínas/imunologia , alfa-Fetoproteínas/análise , Ensaio de Imunoadsorção Enzimática , AdultoRESUMO
To address the challenges associated with formaldehyde emissions in engineered wood adhesives and simultaneously enhance adhesive properties related to water resistance, fire resistance, and mold resistance, a novel environmentally sustainable biomass-based adhesive was formulated. In this work, kraft lignin was carboxymethylated and then blended with the soy protein isolate (SPI)-based adhesive, the dry and wet shear strength of the plywood bonded by the resultant adhesive was enhanced from 1.10 and 0.63 MPa to 1.73 and 1.23 MPa, respectively, resulting in improvements of 157% and 195%. Carboxymethylated lignin (CML) significantly improved the mold resistance and flame-resistance residual rate of the adhesive and decreased the water absorption rate from 190% to 108%. Furthermore, the adhesive exhibits outstanding flame-retardancy, with self-extinguishing capability rendering it suitable for industrial production. In addition, we also evaluated the performances of resulting adhesives cured with different diepoxides and triepoxides, and the comparisons of the adhesive in this work to commercial urea glue and soy protein-based adhesives were conducted. To our delight, the SPI-10CML adhesive presented comparable or even improved performances, showing its promising practical applications such as for fire doors.
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AIMS: This study aimed to investigate environmental factors and genetic variant loci associated with hepatocellular carcinoma (HCC) in Chinese population and construct a weighted genetic risk score (wGRS) and polygenic risk score (PRS). METHODS: A case-control study was applied to confirm the single nucleotide polymorphisms (SNPs) and environmental variables linked to HCC in the Chinese population, which had been screened by meta-analyses. wGRS and PRS were built in training sets and validation sets. Area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were applied to evaluate the performance of the models. RESULTS: A total of 13 SNPs were included in both risk prediction models. Compared with wGRS, PRS had better accuracy and discrimination ability in predicting HCC risk. The AUC for PRS in combination with drinking history, cirrhosis, HBV infection, and family history of HCC in training sets and validation sets (AUC: 0.86, 95% CI: 0.84-0.89; AUC: 0.85, 95% CI: 0.81-0.89) increased at least 20% than the AUC for PRS alone (AUC: 0.63, 95% CI: 0.60-0.67; AUC: 0.65, 95% CI: 0.60-0.71). CONCLUSIONS: A novel model combining PRS with alcohol history, HBV infection, cirrhosis, and family history of HCC could be applied as an effective tool for risk prediction of HCC, which could discriminate at-risk individuals for precise prevention.
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Carcinoma Hepatocelular , Predisposição Genética para Doença , Neoplasias Hepáticas , Polimorfismo de Nucleotídeo Único , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/epidemiologia , Estudos de Casos e Controles , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Fatores de Risco , Povo Asiático/genética , Medição de Risco , Herança Multifatorial , Idoso , Interação Gene-Ambiente , População do Leste AsiáticoRESUMO
The purpose of this study was to identify novel autoantibodies against tumor-associated antigens (TAAs) and explore a diagnostic panel for Ovarian cancer (OC). Enzyme-linked immunosorbent assay was used to detect the expression of five anti-TAA autoantibodies in the discovery (70 OC and 70 normal controls) and validation cohorts (128 OC and 128 normal controls). Machine learning methods were used to construct a diagnostic panel. Serum samples from 81 patients with benign ovarian disease were used to identify the specificity of anti-TAA autoantibodies for OC. In both the discovery and validation cohorts, the expression of anti-CFL1, anti-EZR, anti-CYPA, and anti-PFN1 was higher in patients with OC than that in normal controls. The area under the receiver operating characteristic curve, sensitivity, and specificity of the panel containing anti-CFL1, anti-EZR, and anti-CYPA were 0.762, 55.56%, and 81.31%. The panel identified 53.06%, 53.33%, and 51.11% of CA125 negative, HE4 negative and the Risk of Ovarian Malignancy Algorithm negative OC patients, respectively. The combination of the three anti-TAA autoantibodies can serve as a favorable diagnostic tool for OC and has the potential to be a complementary biomarker for CA125 and HE4 in the diagnosis of ovarian cancer.
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Autoanticorpos , Biomarcadores Tumorais , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/sangue , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Pessoa de Meia-Idade , Adulto , Idoso , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/sangue , Curva ROC , Sensibilidade e Especificidade , Estudos de Casos e Controles , Antígeno Ca-125/sangue , Antígeno Ca-125/imunologiaRESUMO
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. PREVENTION RELEVANCE: We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection.
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Autoanticorpos , Biomarcadores Tumorais , Carcinoma Hepatocelular , Detecção Precoce de Câncer , Vírus da Hepatite B , Hepatite B Crônica , Neoplasias Hepáticas , alfa-Fetoproteínas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/sangue , Detecção Precoce de Câncer/métodos , Ensaio de Imunoadsorção Enzimática , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Hepatite B Crônica/complicações , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/sangue , IdosoRESUMO
PURPOSE: The relationship between circulating 25-hydroxyvitamin D [25(OH)D] and pancreatic cancer has been well studied but remains unclear. The purpose of this study was to elucidate the association between circulating 25(OH)D and pancreatic cancer by using a meta-analytic approach. METHODS: PubMed, Embase, and Wed of Science databases were searched through October 15, 2022. A random or fixed-effects model was used to estimate the pooled odds ratio (OR), risk ratio (RR), hazard ratio (HR) and their 95% confidence intervals (CIs). RESULTS: A total of 16 studies including 529,917 participants met the inclusion criteria, of which 10 reported incidence and 6 reported mortality. For the highest versus lowest categories of circulating 25(OH)D, the pooled OR of pancreatic cancer incidence in case-control studies was 0.98 (95% CI 0.69-1.27), and the pooled HRs of pancreatic cancer mortality in cohort and case-control studies were 0.64 (95% CI 0.45-0.82) and 0.78 (95% CI 0.62-0.95), respectively. The leave-one-out sensitivity analyses found no outliers and Galbraith plots indicated no substantial heterogeneity. CONCLUSION: Evidence from this meta-analysis suggested that high circulating 25(OH)D levels may be associated with decreased mortality but not incidence of pancreatic cancer. Our findings may provide some clues for the treatment of pancreatic cancer and remind us to be cautious about widespread vitamin D supplementation for the prevention of pancreatic cancer.
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Estudos Observacionais como Assunto , Neoplasias Pancreáticas , Vitamina D , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/mortalidade , Humanos , Vitamina D/sangue , Vitamina D/análogos & derivados , Fatores de Risco , IncidênciaRESUMO
To evaluate the potential of zinc finger protein 1 (ZPR1) as a diagnostic biomarker and explore the underlying role for esophageal squamous cell carcinoma (ESCC). A human proteome microarray was customized to identify anti-ZPR1 autoantibody, and enzyme-linked immunosorbent assay (ELISA) was adopted to assess the diagnostic performance of anti-ZPR1 autoantibody in 294 patients with ESCC and 294 normal controls. The expression of ZPR1 protein was measured by immunohistochemistry. The effect of ZPR1 on the proliferation, migration, and invasion of ESCC cells was investigated through CCK-8, wound healing, and Transwell assays. The expression level of anti-ZPR1 autoantibody (fold change = 2.77) in ESCC patients was higher than that in normal controls. The receiver operating characteristic (ROC) analysis manifested anti-ZPR1 autoantibody achieved area under the ROC curve (AUC) of 0.726 and 0.734 to distinguish ESCC from normal controls with sensitivity of 50.0% and 42.3%, and specificity of 91.0% and 92.0% in the test group and validation group, respectively. The positive rate of ZPR1 protein was significantly higher in ESCC tissues (75.5%, 80/106) than paracancerous tissues (9.4%, 5/53). Compared with the human normal esophageal cell line, the expression level of ZPR1 mRNA and protein in ESCC lines (KYSE150, Eca109, and TE1) had an increased trend. The knockdown or overexpression of ZPR1 reduced and enhanced the proliferation, migration, and invasion of ESCC cell, respectively. ZPR1 was a potential immunodiagnostic biomarker for noninvasive detection and could be a promotional factor in tumor progression of ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas/patologia , Biomarcadores , Autoanticorpos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão GênicaRESUMO
Tumor-associated autoantibodies (TAAbs) have demonstrated potential as biomarkers for cancer detection. However, the understanding of their role in hepatocellular carcinoma (HCC) remains limited. In this study, we aimed to systematically collect and standardize information about these TAAbs and establish a comprehensive database as a platform for in-depth research. A total of 170 TAAbs were identified from published papers retrieved from PubMed, Web of Science, and Embase. Following normative reannotation, these TAAbs were referred to as 162 official symbols. The hccTAAb (tumor-associated autoantibodies in hepatocellular carcinoma) atlas was developed using the R Shiny framework and incorporating literature-based and multiomics data sets. This comprehensive online resource provides key information such as sensitivity, specificity, and additional details such as official symbols, official full names, UniProt, NCBI, HPA, neXtProt, and aliases through hyperlinks. Additionally, hccTAAb offers six analytical modules for visualizing expression profiles, survival analysis, immune infiltration, similarity analysis, DNA methylation, and DNA mutation analysis. Overall, the hccTAAb Atlas provides valuable insights into the mechanisms underlying TAAb and has the potential to enhance the diagnosis and treatment of HCC using autoantibodies. The hccTAAb Atlas is freely accessible at https://nscc.v.zzu.edu.cn/hccTAAb/.
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Ascomicetos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Autoanticorpos , Metilação de DNA , Biomarcadores TumoraisRESUMO
Purpose: This study was based on hepatocellular carcinoma (HCC) patients of early-stage to explore the diagnostic capability and possible production causes of anti-GNAS autoantibody. Methods: We evaluated the frequency of anti-GNAS autoantibody in sera from patients with early-stage HCC by enzyme-linked immunosorbent assay (ELISA) and the expression of GNAS protein in early-stage HCC tissues by immunohistochemistry. Western blotting (WB) and real-time polymerase chain reaction (RT-PCR) were utilized to examine the expressions of GNAS protein and mRNA in cell lines. GEO and International Cancer Genome Consortium (ICGC) databases were inquired to explore mRNA expression and mutation of GNAS in HCC tissues. Results: The positive rates of anti-GNAS autoantibody in HCC patients at clinical stage I (78.1 %) and clinical stage II (57.1 %) were all significantly higher than that in healthy control (20 %). There was also a significant difference in GNAS protein expression between HCC and its adjacent normal liver tissues. The results from WB and RT-PCR showed a significant difference at the mRNA level but no statistical difference at the protein level between HCC and normal liver cell lines. The difference in mRNA level between HCC and adjacent normal liver tissues was verified to be significant. Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients. Conclusion: The coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC.
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PURPOSE: This large, single-center, retrospective cohort study was aimed to explore the effect of female body mass index (BMI) on ectopic pregnancy (EP) following fresh and frozen-thawed embryo transfers (ET). METHODS: A total of 27,600 pregnancies after fresh ET and 14,762 pregnancies after frozen-thawed ET were included between January 2010 to June 2022. Women were divided into three groups based on BMI according to the Working Group on Obesity in China (WGOC), International Life Sciences Institute (ILSI): underweight (BMI < 18.5 kg/m2), normal weight (BMI, 18.5-23.9 kg/m2), and overweight or obesity (≥ 24 kg/m2). Compare EP rates among BMI categories in fresh and frozen-thawed ET cycles respectively. Multivariate logistic regression analyses were used to investigate the association between female BMI and EP. RESULTS: The overall EP rates in fresh, and frozen thawed transfer cycles were 2.43% (672/27,600) and 2.82% (417/14,762), respectively. In fresh ET cycles, underweight women yielded a significantly higher EP rate than those with normal and excess weight (3.29% vs. 2.29% vs. 2.54%, P = 0.029). But EP rates did not differ among the three BMI groups (2.72% vs. 2.76% vs. 2.96%, P = 0.782) in frozen-thawed ET cycles. In fresh ET cycles, after adjusting for potential confounding factors, no significant association was found between female BMI and EP occurrence (adjusted OR: 0.98, 95% CI 0.70-1.37, P = 0.894, for BMI 18.5-23.9 kg/m2; adjusted OR: 0.89, 95% CI 0.75-1.06, P = 0.205, for BMI ≥ 24 kg/m2. Reference = BMI < 18.5 kg/m2). CONCLUSION(S): Female BMI did not affect the occurrence of ectopic pregnancy in either fresh or frozen-thawed embryo transfer cycles.
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Gravidez Ectópica , Magreza , Gravidez , Feminino , Humanos , Índice de Massa Corporal , Estudos Retrospectivos , Magreza/epidemiologia , Criopreservação , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/etiologia , Fertilização in vitro/efeitos adversos , Taxa de Gravidez , ObesidadeRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 - 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis. METHODS: A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model. RESULTS: In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%. CONCLUSION: The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.
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MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Autoanticorpos , Biomarcadores Tumorais/metabolismo , Imunoglobulina G , Imunoglobulina M , Antígenos de Neoplasias , Proteínas de NeoplasiasRESUMO
Background: Primary pericardial synovial sarcoma is an extremely rare malignant tumor, and affected patients have a poor prognosis. Only a few cases have been reported in the literature. Case summary: A 34-year-old man was admitted to our hospital with chest tightness and a cough. An echocardiogram revealed a heterogeneous mass with a large pericardial effusion. Further computed tomography (CT) of the chest and cardiac magnetic resonance imaging (CMRI) demonstrated an irregular pericardial mass abutting the left atrium and left ventricle and invading the mediastinal structures. Pathology results showed that the tumor was a monophasic synovial sarcoma. The patient underwent chemotherapy and survived for 17 months. Discussion: Many cardiac tumors are clinically asymptomatic or nonspecific, and they are frequently detected or diagnosed at an advanced stage of the disease. Multimodal cardiac imaging facilitates the detection and assessment of cardiac tumors. In particular, CMRI is considered as a superior imaging tool, because it provides high tissue contrast and can detect invasion of the myocardium. We describe the clinical details and multimodal imaging features of a rare primary pericardial synovial sarcoma, hoping to provide guidance for the diagnosis of similar cases in the future.
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Dexmedetomidine has been shown to protect against cerebral ischemia-reperfusion injury (CIRI). Nevertheless, the precise mechanism is obscure. In order to explore the effect of dexmedetomidine pre-conditioning on autophagy against CIRI in rats, middle cerebral artery occlusion (MCAO) was conducted to establish cerebral ischemia-reperfusion (I/R) model in male SD rats with 2 h ischemia and 24 h reperfusion. Dexmedetomidine was delivered to rats at 10, 50 and 100 µg/kg doses respectively, and LY294002, a PI3K/Akt/mTOR pathway inhibitor, was administered at 10 mg/kg intraperitoneally 30 min before MCAO. Neurological deficit score was assessed and cerebral infarct size was detected by TTC staining. Morris water maze (MWM) was performed to estimate spatial learning and memory ability. Furthermore, to detect activity of PI3K/Akt/mTOR pathway and autophagy, p-Akt, p-mTOR, Beclin-1 and LC3 were measured by western blot. Our findings revealed that 50 and 100 µg/kg of dexmedetomidine pretreatment could improve the neurological deficit score and reduce cerebral infarct size after CIRI, while these effects were markedly suppressed by LY294002. In MWM test, dexmedetomidine was confirmed to shorten escape latency and increase times across platform after CIRI. Nevertheless, LY294002 pretreatment eliminated the improvement of dexmedetomidine on spatial learning and memory ability. Furthermore, dexmedetomidine pretreatment reduced ratios of Beclin-1 and LC3II/LC3I and elevated p-Akt/Akt and p-mTOR/mTOR after CIRI. However, above effects of dexmedetomidine were partly reversed by LY294002. Overall, dexmedetomidine pretreatment exerted neuroprotection against CIRI in rats by attenuating autophagy via the PI3K/Akt/mTOR pathway.
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Dexmedetomidina , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Ratos Sprague-Dawley , Proteína Beclina-1 , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Infarto Cerebral/tratamento farmacológico , Autofagia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismoRESUMO
Adverse cardiac remodeling after acute myocardial infarction is the most important pathological mechanism of heart failure and remains a major problem in clinical practice. Cardiac macrophages, derived from tissue resident macrophages and circulating monocyte, undergo significant phenotypic and functional changes following cardiac injury and play crucial roles in inflammatory response and tissue repair response. Currently, numerous studies indicate that epigenetic regulatory factors and transcription factors can regulate the transcription of inflammatory and reparative genes and timely conversion of inflammatory macrophages into reparative macrophages and then alleviate cardiac remodeling. Accordingly, targeting transcriptional regulation of macrophages may be a promising option for heart failure treatment. In this review, we not only summarize the origin and function of cardiac macrophages, but more importantly, describe the transcriptional regulation of macrophages in heart failure, aiming to provide a potential therapeutic target for heart failure.
RESUMO
BACKGROUND: TGF-ß-induced factor homeobox 2 (TGIF2) is a transcription regulator that is phosphorylated by EGFR/ERK signaling. However, the functions of phosphorylated (p)-TGIF2 in cancer are largely unknown. Here, we investigated the roles of p-TGIF2 in promoting epithelial-mesenchymal transition (EMT) and metastasis in lung adenocarcinoma (LUAD). METHODS: In vitro and in vivo experiments were conducted to investigate the role of TGIF2 in LUAD EMT and metastasis. Dual-luciferase reporter and ChIP assays were employed to observe the direct transcriptional regulation of E-cadherin by TGIF2 and HDAC1. Co-immunoprecipitation was performed to identify the interaction between TGIF2 and HDAC1. RESULTS: Downregulating the expression of TGIF2 inhibited LUAD cell migration, EMT and metastasis in vitro and in vivo. Phosphorylation of TGIF2 by EGFR/ERK signaling was required for TGIF2-promoted LUAD EMT and metastasis since phosphorylation-deficient TGIF2 mutant lost these functions. Phosphorylation of TGIF2 was necessary to recruit HDAC1 to the E-cadherin promoter sequence and subsequently suppress E-cadherin transcription. Meanwhile, inhibition of HDAC1 repressed the TGIF2 phosphorylation-induced migration and EMT of LUAD cells. In xenograft mouse models, both inhibition of ERK and HDAC1 could significantly inhibited TGIF2-enhanced metastasis. Furthermore, TGIF2-positive staining was significantly correlated with E-cadherin-negative staining in human lung cancer specimens. CONCLUSIONS: Our study reveals the novel function of p-TGIF2 in promoting EMT and metastasis in LUAD; p-TGIF2 could be a potential therapeutic target to inhibit LUAD metastasis.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Transição Epitelial-Mesenquimal/genética , Fosforilação , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/patologia , Caderinas/genética , Caderinas/metabolismo , Receptores ErbB/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismoRESUMO
The identification of the high-efficiency and non-invasive biomarkers for hepatocellular carcinoma (HCC) detection is urgently needed. This study aims to screen out potential autoantibodies to tumor-associated antigens (TAAbs) and to assess their diagnostic value for HCC. Fifteen potential TAAbs were screened out from the Human Proteome Microarray by 30 HCC sera and 22 normal control sera, of which eight passed multiple-stage validations by ELISA with a total of 1625 human serum samples from normal controls (NCs) and patients with HCC, liver cirrhosis, chronic hepatitis B, gastric cancer, esophageal cancer, and colorectal cancer. Finally, an immunodiagnostic model including six TAAbs (RAD23A, CAST, RUNX1T1, PAIP1, SARS, PRKCZ) was constructed by logistic regression, and yielded the area under curve (AUC) of 0.835 and 0.788 in training and validation sets, respectively. The serial serum samples from HCC model mice were tested to explore the change in TAAbs during HCC formation, and an increasing level of autoantibodies was observed. In conclusion, the panel of six TAAbs can provide potential value for HCC detection, and the strategy to identify novel serological biomarkers can also provide new clues in understanding immunodiagnostic biomarkers.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/diagnóstico , Autoanticorpos , Proteoma , Biomarcadores Tumorais , Antígenos de Neoplasias , Fatores de Iniciação de Peptídeos , Proteínas de Ligação a RNA , Proteínas de Ligação a DNA , Enzimas Reparadoras do DNARESUMO
Adherence to annual fundus examinations in the Chinese population with diabetes and its correlates have not been investigated. The present study obtained data for the first nationally representative survey in China, China Health and Retirement Longitudinal Survey (CHARLS), which collected a wide range of data every 2 years, including demographic, socioeconomic, medical and lifestyle-related information. The adherence rates to annual fundus exams across four waves (2011−2018) were assessed. Univariate and multivariable logistic regressions were used to determine factors associated with adherence. The adherence rates to annual fundus examinations of ou study population were 23.6% in 2011, 15.3% in 2013, 17.5% in 2015 and 21.5% in 2018, respectively. Consistent results over four waves showed that non-adherent patients had a relatively lower educational level, insufficient diabetes medication use, fewer non-medication treatments and irregular physical examination compared to those who were adherent to the annual fundus exam (all p values < 0.05). These variables were further identified as factors associated with adherence according to univariate and multivariate logistic regression analyses (all p values < 0.05). The present study provides explicit evidence that the adherence rate to annual fundus examinations among Chinese population with diabetes is worryingly low. Insufficient educational attainment, especially specific diabetes education, has a negative impact on patients' adherence to clinical guideline for eye health.