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Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.
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Esquistosomiasis Japónica , Esquistosomiasis , Humanos , Ratones , Animales , Interleucina-4 , Cirrosis Hepática , Esquistosomiasis/complicaciones , Hígado , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , InmunidadRESUMEN
@#[摘 要] 目的:探究驱动蛋白-13家族2C(KIF2C)对肝细胞癌(HCC)细胞增殖、侵袭和迁移以及人脐静脉内皮细胞(HUVEC)血管生成的影响,为HCC治疗提供潜在靶点。方法:用数据库数据分析KIF2C mRNA和蛋白在HCC组织中的表达及其与血管生成相关因子(VEGFR2和HIF-1α)表达的相关性,常规培养人正常肝细胞QSG-7701、HUVEC和HCC细胞Huh-7、Hep3B2.1-7,用Lipofectamine 3000转染试剂将sh-NC和sh-KIF2C转染至Huh-7、Hep3B2.1-7细胞,qPCR检测各组QSG-7701、Huh-7和Hep3B2.1-7细胞中KIF2C mRNA的表达,WB法检测各组细胞中KIF2C蛋白的表达,细胞克隆形成实验检测敲低KIF2C对Hep3B2.1-7和Huh-7细胞克隆形成的影响,小管生成实验检测敲低KIF2C表达的Huh-7和Hep3B2.1-7细胞的条件培养液对HUVEC血管生成能力的影响。结果:数据库分析结果显示,KIF2C mRNA和蛋白在HCC组织中均呈高表达(均P<0.01),用qPCR和WB法检测人HCC中KIF2C mRNA和蛋白的表达水平,结果显示其mRNA和蛋白在各HCC细胞中也呈高表达(均P<0.01),与数据库数据分析结果相符。数据库数据分析还显示,KIF2C与HCC组织中VEGFR2、HIF-1α的表达水平呈正相关(P<0.05或P<0.01)。成功构建了稳定低表达KIF2C的Huh-7和Hep3B2.1-7细胞(均P<0.01),敲低KIF2C表达均可明显抑制Huh-7和Hep3B2.1-7细胞的增殖能力(均P<0.01)、侵袭和迁移能力(均P<0.01),敲低KIF2C表达的HCC细胞条件培养液均可显著抑制体外HUVEC的血管生成能力(P<0.05或P<0.01)。结论:KIF2C可促进Huh-7和Hep3B2.1-7细胞增殖、侵袭和迁移以及HUVEC血管生成的能力,提示KIF2C可能是治疗HCC的潜在靶点。
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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, influencing numerous regulatory axes and extrahepatic vital organs. The molecular mechanisms that lead to the progression of NAFLD remain unclear and knowledge on the pathways causing hepatocellular damage followed by lipid accumulation is limited. Recently, a number of studies have shown that mRNA N6-methyladenosine (m6A) modification contributes to the progression of NAFLD. In this review, we summarize current knowledge on m6A modification in the metabolic processes associated with NAFLD and discuss the challenges of and prospects for therapeutic avenues based on m6A regulation for the treatment of liver disease.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Adenosina/metabolismo , Adenosina/uso terapéutico , ARN/metabolismo , ARN/uso terapéutico , Hígado/metabolismoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients' outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. OBJECTIVE: This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients' clinical characteristics and potential role in HCC development. METHODS: Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate involvement in HCC development. RESULTS: FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p< 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823-0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p< 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. CONCLUSION: This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Regulación hacia Arriba , Resultado del Tratamiento , Proliferación Celular/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Proteínas de Unión a Tacrolimus/genética , Proteínas de Unión a Tacrolimus/metabolismoRESUMEN
Cancer is characterized by metabolic reprogramming, which is a hot topic in tumor treatment research. Cancer cells alter metabolic pathways to promote their growth, and the common purpose of these altered metabolic pathways is to adapt the metabolic state to the uncontrolled proliferation of cancer cells. Most cancer cells in a state of nonhypoxia will increase the uptake of glucose and produce lactate, called the Warburg effect. Increased glucose consumption is used as a carbon source to support cell proliferation, including nucleotide, lipid and protein synthesis. In the Warburg effect, pyruvate dehydrogenase activity decreases, thereby disrupting the TCA cycle. In addition to glucose, glutamine is also an important nutrient for the growth and proliferation of cancer cells, an important carbon bank and nitrogen bank for the growth and proliferation of cancer cells, providing ribose, nonessential amino acids, citrate, and glycerin necessary for cancer cell growth and proliferation and compensating for the reduction in oxidative phosphorylation pathways in cancer cells caused by the Warburg effect. In human plasma, glutamine is the most abundant amino acid. Normal cells produce glutamine via glutamine synthase (GLS), but the glutamine synthesized by tumor cells is insufficient to meet their high growth needs, resulting in a "glutamine-dependent phenomenon." Most cancers have an increased glutamine demand, including breast cancer. Metabolic reprogramming not only enables tumor cells to maintain the reduction-oxidation (redox) balance and commit resources to biosynthesis but also establishes heterogeneous metabolic phenotypes of tumor cells that are distinct from those of nontumor cells. Thus, targeting the metabolic differences between tumor and nontumor cells may be a promising and novel anticancer strategy. Glutamine metabolic compartments have emerged as promising candidates, especially in TNBC and drug-resistant breast cancer. In this review, the latest discoveries of breast cancer and glutamine metabolism are discussed, novel treatment methods based on amino acid transporters and glutaminase are discussed, and the relationship between glutamine metabolism and breast cancer metastasis, drug resistance, tumor immunity and ferroptosis are explained, which provides new ideas for the clinical treatment of breast cancer.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Glutamina/metabolismo , Línea Celular Tumoral , Aminoácidos , Carbono , Glucosa/metabolismoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. OBJECTIVE: To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. METHODS: Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. RESULTS: LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo. CONCLUSION: The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Humanos , Animales , ARN Largo no Codificante/genética , Carcinoma Hepatocelular/genética , Regulación hacia Arriba , Hibridación Fluorescente in Situ , Neoplasias Hepáticas/genética , Proliferación Celular/genéticaRESUMEN
Purpose: Hepatitis B (HBV)-infected hepatocellular carcinoma is one of the most common cancers, and it has high incidence and mortality rates worldwide. The incidence of hepatocellular carcinoma has been increasing in recent years, and existing treatment modalities do not significantly improve prognosis. Therefore, it is important to find a biomarker that can accurately predict prognosis. Methods: This study was analyzed using the The Cancer Genome Atlas (TCGA) database and validated by the International Cancer Genome Consortium (ICGC) database. The STRING database was used to construct a gene co-expression network and visualize its functional clustering using Cytoscape. A prognostic signature model was constructed to observe high and low risk with prognosis, and independent prognostic factors for HBV-infected hepatocellular carcinoma were identified by Cox regression analysis. The independent prognostic factors were then analyzed for expression and survival, and their pathway enrichment was analyzed using gene set enrichment analysis (GSEA). Results: 805 differentially expressed genes (DEGs) were obtained by differential analysis. Protein-protein interaction (PPI) showed that DEGs were mostly clustered in functional modules, such as cellular matrix response, cell differentiation, and tissue development. Prognostic characterization models showed that the high-risk group was associated with poor prognosis, while Cox regression analysis identified ASF1B as the only independent prognostic factor. As verified by expression and prognosis, ASF1B was highly expressed in HBV-infected hepatocellular carcinoma and led to a poor prognosis. GSEA showed that high ASF1B expression was involved in cell cycle-related signaling pathways. Conclusion: Bioinformatic analysis identified ASF1B as an independent prognostic factor in HBV-infected hepatocellular carcinoma, and its high expression led to a poor prognosis. Furthermore, it may promote hepatocellular carcinoma progression by affecting cell cycle-related signaling pathways.
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Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.
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Lupus Eritematoso Sistémico , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Biomarcadores , Diferenciación Celular , HumanosRESUMEN
INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus-2 pandemic is critically challenging the whole world. The real-time reverse transcriptase-polymerase chain reaction is the most widely used confirmatory test for COVID-19 detection. This study aimed to find out the prevalence of COVID-19 infection detected by gold standard reverse transcriptase-polymerase chain reaction test in a tertiary care center of Nepal. METHODS: A descriptive cross-sectional study was conducted in Karnali Academy of Health Sciences from May to August 2020 after taking ethical approval from the Institutional Review Committee of Karnali Academy of Health Sciences, Jumla. Convenient sampling was used. A total of 361 participants enrolled in this study who have done real-time reverse transcriptase-polymerase chain reaction for screening of COVID-19 infection. Also, a designated questionnaire was obtained from persons with a travel history and close contact. Statistical Package for the Social Sciences software was used for the statistical analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: The prevalence of COVID-19 was 167 (46.3%) (95% Confidence Interval= 41.16-51.44) by real-time reverse transcriptase-polymerase chain reaction test. Out of 361 samples, 339 (93.9%) were male and 22 (6%) were female. The highest frequency of the participants belongs to the age groups of 20-40 years. CONCLUSIONS: The findings showed a high prevalence of COVID-19 detected by reverse transcriptase-polymerase chain reaction test. Further studies are necessary to improve the precision of prevalence estimations.
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COVID-19 , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , ADN Polimerasa Dirigida por ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Centros de Atención Terciaria , Adulto JovenRESUMEN
AIMS: This study aimed to reveal the functional role of LINC00485 in hepatocellular carcinoma (HCC). MATERIALS & METHODS: 210 serum samples from Zhongnan Hospital of Wuhan University were employed to evaluate clinical value of LINC00485. Bioinformatics analysis was adopted to explore its potential mechanisms. RESULTS: LINC00485 was confirmed to be upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve revealed its prognostic and diagnostic roles. The combination of serum LINC00485 with AFP can remarkably improve diagnostic ability of HCC. Exploration of the underlying mechanism demonstrated that LINC00485 might exert pro-oncogenic activity by LINC00485-three miRNAs-four mRNAs network. CONCLUSIONS: Our study unveiled that upregulated LINC00485 could act as a potential diagnostic and prognostic biomarker and provide a novel insight into the molecular mechanisms of LINC00485 in HCC pathogenesis.
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Background: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Early detection of HCC can significantly improve patients' outcomes. An increasing number of studies have validated that Homer is dysregulated in cancers and may serve as diagnostic markers. In the present study, we investigated the expression profile and diagnostic significance of Homer2 and Homer3 in hepatitis B virus-induced HCC (HBV-HCC). Methods: Quantitative real-time PCR (QRT-PCR), western blot analysis and immunohistochemistry analysis. Results: Homer2 and Homer3 were downregulated in HCC. The expression of Homer2 was associated with tumor differentiation grade (P= 0.012) and total protein (TP) level (P= 0.032). Homer3 was related to tumor size (P= 0.010), tumor nodes (P= 0.026) and γ-glutamyl transferase (GGT) level (P= 0.001). The receiver operating characteristic curve analyses indicated that the combination of Homer2, Homer3 and AFP possessed a high accuracy (AUC=0.900) to diagnose HCC cases from healthy controls. Conclusion: Our data indicated that Homer2 and Homer3 were downregulated in HCC and might be potential diagnostic marker for HCC.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%-30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear. METHODS: The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection. RESULTS: A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis. CONCLUSION: Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.
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COVID-19/metabolismo , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Miocitos Cardíacos/metabolismo , RNA-Seq , SARS-CoV-2/metabolismo , Línea Celular , Células Madre Embrionarias Humanas/metabolismo , Células Madre Embrionarias Humanas/patología , Células Madre Embrionarias Humanas/virología , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Células Madre Pluripotentes Inducidas/virología , Miocitos Cardíacos/patología , Miocitos Cardíacos/virología , Tratamiento Farmacológico de COVID-19RESUMEN
Aims:This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). Materials and methods:A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. Results:LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA-miRNA-mRNA network.Conclusions: Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Pronóstico , ARN Mensajero/genética , Curva ROC , Análisis de SupervivenciaRESUMEN
INTRODUCTION: The persistence positivity detected for severe acute respiratory syndrome coronavirus 2 ribonucleic acid by real-time reverse transcriptase-polymerase chain reaction test in asymptomatic coronavirus disease 2019 positive patients has attracted a lot of attention. There is limited data on the duration of viral shedding. We aimed to determine the proportion of coronavirus disease patients with persistent positivity of real-time reverse transcriptase-polymerase chain reaction test in a teaching hospital of Nepal. METHODS: A descriptive cross-sectional study was conducted using medical records from May to September 2020 in a teaching hospital of Nepal. The study was approved by the Institutional Review Committee of Karnali Academy of Health Sciences (Reference no 077/078/03). Convenient sampling method was used. Data was analysed by Statistical Package for the Social Sciences. Point estimate at 90% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Of the total 95 cases, 9 (9.5%) cases (4.6-14.4 at 90% Confidence Interval), were repeat positive after achieving the first negative. The mean day required of achieving the last negative for the repeat positive group was 62.11±3.95, range (60-70 days). The mean time duration for the virus shedding was found to be 20.43±12.19 days (range 7-60 days) after the first positive test result. CONCLUSIONS: This study concludes that there might be a persistent positivity of the polymerase chain reaction test among patients with COVID-19. The majority of the patients were test positive for 8-14 days, and some were positive till 60-70 days.
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COVID-19 , Estudios Transversales , Hospitales de Enseñanza , Humanos , ADN Polimerasa Dirigida por ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2RESUMEN
Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases worldwide. Available biomarkers are not sensitive enough for the diagnosis of HCC, hence seeking new biomarkers of HCC is urgent and challenging. The purpose of this study was to investigate the role of F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) through a functional network and inquire into its diagnostic and prognostic value in HCC. A comprehensive strategy of genomic data mining, bioinformatics and experimental validation was used to evaluate the clinical value of FBXL19-AS1 in the diagnosis and prognosis of HCC and to identify the pathways in which FBXL19-AS1 might be involved. FBXL19-AS1 was up-regulated in HCC tissues, and its high expression was associated with TNM stage and poor prognosis of HCC patients. The combination of FBXL19-AS1 and alpha-fetoprotein (AFP) in plasma could prominently improve the diagnostic validity for HCC. FBXL19-AS1 might stabilize FBXL19 to reduce the amount of macrophage M1, and then promote the occurrence and development of HCC. Meanwhile, FBXL19-AS1 might participate in regulating HCC related pathways through FBXL19-AS1-miRNA-mRNA network. Our findings indicated that FBXL19-AS1 not only serves as a potential biomarker for HCC diagnosis and prognosis, but also might be functionally carcinogenic.
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BACKGROUND: Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown. METHODS: Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality. RESULTS: Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78). CONCLUSIONS: High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.
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Equilibrio Ácido-Base , Infarto Cerebral/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Infarto Cerebral/diagnóstico , Infarto Cerebral/mortalidad , Infarto Cerebral/fisiopatología , Enfermedad Crítica , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and functional mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly. METHODS: An integrative strategy of meta-analysis, bioinformatics, and wet-lab approach was used to explore the diagnostic and prognostic significance of POU5F1 in various types of tumors, especially in LIHC. Meta-analysis was utilized to investigate the impact of POU5F1 on prognosis and clinicopathological parameters in various cancers. The expression level and diagnostic value of POU5F1 were assessed by qPCR in plasma collected from LIHC patients and controls. The correlation between POU5F1 and tumor infiltrating immune cells (TIICs) in LIHC was evaluated by CIBERSORT. Gene set enrichment analysis (GSEA) was performed based on TCGA. Hub genes and related pathways were identified on the basis of co-expression genes of POU5F1. RESULTS: Elevated POU5F1 was associated with poor OS, DFS, RFS, and DSS in various cancers. POU5F1 was confirmed as an independent risk factor for LIHC and correlated with tumor occurrence, stage, and invasion depth. The combination of POU5F1 and AFP in plasma was with high diagnostic validity (AUC = 0.902, p < .001). Specifically, the level of POU5F1 was correlated with infiltrating levels of B cells, T cells, dendritic cells, and monocytes in LIHC. GSEA indicated that POU5F1 participated in multiple cancer-related pathways and cell proliferation pathways. Moreover, CBX3, CCHCR1, and NFYC were filtered as the central hub genes of POU5F1. CONCLUSION: Our study identified POU5F1 as a pan-cancer gene that could not only be a prognostic and diagnostic biomarker in various cancers, especially in LIHC, but functionally carcinogenic in LIHC.
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Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Algoritmos , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Estudios de Casos y Controles , Biología Computacional , Bases de Datos Genéticas , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Factor 3 de Transcripción de Unión a Octámeros/sangre , Valor Predictivo de las Pruebas , Mapas de Interacción de Proteínas , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Lung cancer is the severe leading cause of cancer-related mortality worldwide. Early detection of lung cancer can significantly increase their survival rate. However, conventional lung cancer screening methods such as sputum cytology, chest X-rays, low-dose computed tomography, positron emission tomography, and magnetic resonance imaging, are radiational, and also expensive methods. Similarly, lung tumor tissue as invasive and difficult to obtain and potentially risky procedures, there is the immediate need of non-invasive, novel sensitive and reliable blood-based tumor markers which now has become an important area on research. This review will mainly focus on recently identified circulating biomarkers: circulating tumor cells, circulating tumor deoxyribonucleic acid, tumor-derived exosomes, circulating ribonucleic acid and micro ribonucleic acid, and tumoreducated platelets which may enable earlier diagnosis of lung cancer and their application in clinical practices.
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Biomarcadores de Tumor/sangre , Citodiagnóstico , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares , Plaquetas/patología , MicroARN Circulante/sangre , ADN Tumoral Circulante/sangre , Citodiagnóstico/métodos , Exosomas/patología , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes/patología , ARN Neoplásico/sangreRESUMEN
A method based on microfluidic voltage-assisted liquid desorption electrospray ionization-tandem mass spectrometry (VAL-DESI-MS/MS) has been developed for fast quantification of free amino acids in food. Food extracts were transferred to the microfluidic platform and analyzed by liquid desorption ESI-MS/MS. Deuterated aspartic acid (i.e., 2,2,3-d3-Asp) was used as internal standard for analysis. The method had linear calibration curves with r2 values > 0.998. Limits of detection were at the level of sub µM for the amino acids tested, i.e., glutamic acid (Glu), arginine (Arg), tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe). To validate the proposed method in food analysis, extracts of Cordyceps fungi were analyzed. Amino acid contents were found in the range from 0.63 mg/g (Tyr in Cordyceps sinensis) to 4.44 mg/g (Glu in Cordyceps militaris). Assay repeatability (RSD) was ≤ 5.2% for all the five amino acids measured in all the samples analyzed. Recovery was found in the range from 95.8 to 105.1% at two spiking concentrations of 0.250 mg/g and 1.00 mg/g. These results prove that the proposed microfluidic VAL-DESI-MS/MS method offers a quick and convenient means of quantifying free amino acids with accuracy and repeatability. Therefore, it may have potential in food analysis for nutritional and quality assessment purposes. Graphical abstract.
Asunto(s)
Aminoácidos/análisis , Análisis de los Alimentos/métodos , Microfluídica , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Hepatocellular carcinoma (HCC) is one of the most malignant cancer with high morbidity and mortality which lead to a serious burden to society. AFP (alpha-fetoprotein) is the most widely used serum biomarker to detect HCC worldwide. However, no AFP elevation have been found in many HCC and AFP analysis can't be used to screen HCC in these cases. Currently, many studies have been carried out to find reliable biomarker in diagnosing AFP-negative HCC. Such biomarker would help the diagnosis of AFP-negative HCC, ensuring the timely initiation of treatment. In this review, we highlight the important role of biomarkers that can differentiate AFP-negative HCCs, and discuss their potential clinical applications as biomarkers for the diagnosis of AFP-negative HCC.