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Bovine colostrum provides newborn calves with strong passive immunity, which will further affect the immunity of their offspring. Compared with other commercial dairy products, bovine colostrum emphasizes the limit of aflatoxin M1, pathogenic bacteria, microorganisms, antibiotics, stimulants, and other items, so it is safe to use. There are many reports that the use of bovine colostrum as a breast milk fortifier for preterm infants provides necessary immune support for premature infants, but the selection of bovine colostrum products chosen must be free of Bacillus cereus because they are very dangerous for premature infants. This also emphasizes that for the bovine colostrum that is used in preterm infants, more clinical research support is needed. At the same time, it should also be emphasized that the composition of BC is different from that of human colostrum, in particular, the main protein of BC is casein, while the main protein in breast milk is whey protein, especially α-lactalbumin, which together with ovalbumin is still the reference protein with the best biological value, especially for muscles. Therefore, bovine colostrum is currently not a complete substitute for breast milk. In recent years, in addition to reports of bovine colostrum use in preterm infants, studies have also found that bovine colostrum has immunomodulatory and promoting effects in adolescents, adults, and the elderly. This suggests that bovine colostrum has the potential to provide appropriate immune support for people of all ages. Therefore, this study aimed to evaluate the quality of nutritional characteristics of bovine colostrum on three dimensions. The effects of bovine colostrum on people of all ages is a narrative review of the effects of bovine colostrum on immunity in people of all ages. This review identified several classes of immunoactive substances in bovine colostrum, including immunoglobulins, cytokines, and enzymes, and compared the nutritional composition of bovine colostrum with mature milk, colostrum and mature milk in full-term breast milk, and colostrum and mature milk in preterm breast milk, to demonstrate that bovine colostrum provides a rich range of immunoactive components. In addition, the influencing factors affecting the quality of bovine colostrum (immunoglobulin) were reviewed, and it was found that individual differences, environmental factors, and processing methods had a great impact on the quality of BC. More importantly, the immunomodulatory effects of bovine colostrum in people of all ages were reviewed in detail (with an emphasis on preterm infants and immunocompromised children in neonates) as evidence to support the immunity effects of colostrum in people of all ages. This review hopes to use the above evidence to make people understand the health role of bovine colostrum as having a human immunomodulatory effect, and at the same time, when seeing the potential value of bovine colostrum in the future, the limitations of its application should also be deeply re-explored, such as lactose intolerance, allergies, etc., to provide effective solutions for the wide application of bovine colostrum.
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Colostro , Colostro/imunologia , Animais , Bovinos , Humanos , Feminino , Recém-Nascido , Adulto , Recém-Nascido Prematuro/imunologia , Leite Humano/imunologia , Leite Humano/química , Adolescente , Gravidez , Criança , IdosoRESUMO
Ammonia production by electrocatalytic nitrate reduction reaction (NO3RR) in water streams is anticipated as a zero-carbon route. Limited by dilute nitrate in natural sewage and the electrostatic repulsion between NO3 - and cathode, NO3RR can hardly be achieved energy-efficiently. The hydrophilic Cu@CuCoO2 nano-island dispersed on support can enrich NO3 - and produce a sensitive current response, followed by electrosynthesis of ammonia through atomic hydrogen (*H) is reported. The accumulated NO3 - can be partially converted to NO2 - without external electric field input, confirming that the Cu@CuCoO2 nano-island can strongly bind NO3 - and then trigger the reduction via dynamic evolution between Cu-Co redox sites. Through the identification of intermediates and theoretical computation. it is found that the N-side hydrogenation of *NO is the optimal reaction step, and the formation of NâN dimer may be prevented. An NH3 product selectivity of 93.5%, a nitrate conversion of 96.1%, and an energy consumption of 0.079 kWh gNH3 -1 is obtained in 48.9 mg-N L-1 naturally nitrate-polluted streams, which outperforms many works using such dilute nitrate influent. Conclusively, the electrocatalytic system provides a platform to guarantee the self-sufficiency of dispersed ammonia production in agricultural regions.
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Large emissions of atmospheric carbon dioxide (CO2) are causing climatic and environmental problems. It is crucial to capture and utilize the excess CO2 through diverse methods, among which the microbial electrosynthesis (MES) system has become an attractive and promising technology to mitigate greenhouse effects while reducing CO2 to high-value chemicals. However, the biological conversion and metabolic pathways through microbial catalysis have not been clearly elucidated. This review first introduces the main acetogenic bacteria for CO2 reduction and extracellular electron transfer mechanisms in MES. It then intensively analyzes the CO2 bioconversion pathways and carbon chain elongation processes in MES, together with energy supply and utilization. The factors affecting MES performance, including physical, chemical, and biological aspects, are summarized, and the strategies to promote and regulate bioconversion in MES are explored. Finally, challenges and perspectives concerning microbial electrochemical carbon sequestration are proposed, and suggestions for future research are also provided. This review provides theoretical foundation and technical support for further development and industrial application of MES for CO2 reduction.
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Bactérias , Dióxido de Carbono , Dióxido de Carbono/metabolismo , Eletrodos , Transporte de Elétrons , Bactérias/metabolismo , CatáliseRESUMO
The proliferation of antibiotic-resistance genes is a result of the rise in the discharge of residual antibiotics into waterbodies from a variety of sources. Antibiotic removal by microalgae-bacteria consortium has been shown to be effective, therefore, there is a need to understand the involved microbial processes. This review summarizes the microbiological removal mechanisms of antibiotics by the microalgae-bacteria consortium, such as biosorption, bioaccumulation, and biodegradation. Factors that influence antibiotic removal are discussed. Co-metabolism of nutrients and antibiotics in the microalgae-bacteria consortium and the metabolic pathways revealed by omics technologies are also highlighted. Furthermore, the responses of microalgae and bacteria to antibiotic stress are elaborated, including reactive oxidizing species (ROS) generation and its effects on photosynthesis machinery, antibiotic stress tolerance, microbial community shift, and the emergence of antibiotic resistance genes (ARGs). Finally, we offer a prospective solutions for the optimization and applications of microalgae-bacteria symbiotic systems for antibiotic removal.
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Antibacterianos , Microalgas , Antibacterianos/farmacologia , Estudos Prospectivos , Bactérias , FotossínteseRESUMO
BACKGROUND AND OBJECTIVES: In patients with colorectal cancer and clinically suspected para-aortic lymph node metastasis, the survival benefit of para-aortic lymphadenectomy is unknown. We conducted a meta-analysis and systematic review to investigate it. METHODS: PubMed, Web of Science, and EMBASE were searched until January 2000 to April 2022 to identify studies reporting overall survivals, complication rates, and hazard ratios of prognostic factors in patients with colorectal cancer undergoing para-aortic lymphadenectomy, and those data were pooled. RESULTS: Twenty retrospective studies (1021 patients undergoing para-aortic lymphadenectomy) met the inclusion criteria. Meta-analysis indicates that participants undergoing para-aortic lymphadenectomy were associated with 5-year survival benefit, compared to those not receiving para-aortic lymphadenectomy (odds ratio = 3.73, 95% confidence interval: 2.05-6.78), but there was no significant difference in complication rate (odds ratio = 0.97, 95% confidence interval: 0.46-2.08). Further analysis of para-aortic lymphadenectomy group showed that 5-year survival of the positive group with pathologically para-aortic lymph node metastasis was lower than that of the negative group (odds ratio = 0.19, 95% confidence interval: 0.11-0.31). Moreover, complete resection (odds ratio = 5.26, 95% confidence interval: 2.02-13.69), para-aortic lymph node metastasis (≤4) (hazard ratio = 1.88, 95% confidence interval: 0.97-3.62), and medium-high differentiation (hazard ratio = 2.98, 95% confidence interval: 1.48-5.99) were protective factors for survival. Preoperative extra-retroperitoneal metastasis was associated with poorer relapse-free survival (hazard ratio = 1.85, 95% confidence interval: 1.10-3.10). CONCLUSION: Para-aortic lymphadenectomy had promising clinical efficacy in prolonging survival rather than complication rate in patients with colorectal cancer and clinically diagnostic para-aortic lymph node metastasis. Further prospective studies should be performed. TRIAL REGISTRATION: PROSPERO: CRD42022379276.
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Neoplasias Colorretais , Excisão de Linfonodo , Humanos , Neoplasias Colorretais/cirurgia , Metástase Linfática , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Gastric cancer is the fifth most common cancer worldwide. With the development of immunotherapy, especially the application of immune checkpoint inhibitors (ICIs), the prognosis of advanced gastric cancer has improved. At present, ICIs combined with other therapies or dual ICI strategies in the treatment of advanced gastric cancer have shown clinical effectiveness and controllable safety. In addition, predictive biomarkers facilitate the precise selection of patients. Therefore, it is crucial to explore rational combinations and reliable predictive biomarkers for ICI therapy. This article reviews the recent advances in ICIs and relevant predictive biomarkers in the treatment of gastric cancer.
In recent years, with the application of immunotherapy, clinical efficacy in gastric cancer has been effectively improved. At present, it is encouraging that immunotherapy combined with chemotherapy has become the first choice for the treatment of patients with advanced gastric cancer. However, researchers remain committed to exploring the efficacy of immunotherapy in combination with various therapies. Equally important, the identification of biomarkers can facilitate the selection of patients suitable for immunotherapy. This article summarizes important immunotherapy clinical trials and discusses therapeutic combinations and biomarkers being explored.
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Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Gástricas/terapia , Biomarcadores , Imunoterapia , PrognósticoRESUMO
Background: The incidence of early-onset colorectal cancer (EOCRC) has increased globally since the early 1990s. Comprehensively examining the risk factors would be helpful for risk stratification and the development of personalized colorectal cancer screening strategies. Methods: We performed a prospective study of the Chinese population aged 30-50 years to identify potential risk factors during a median follow-up of 9.1 years. We compared the distribution of demographic characteristics, lifestyle factors, dietary habits, and medical history among 222 EOCRC cases and 87,833 normal controls. Multivariate adjusted Cox hazard models were used for estimating EOCRC risks of each risk factor. Results: Our final analyses indicated that participants with a higher body mass index (HR, 1.04; 95% CI:1.00,1.08), regular alcohol consumption (HR, 1.69; 95% CI: 1.12, 2.91), higher intake of fish (HR, 1.64; 95% CI: 1.01, 2.67), hypertension (HR, 1.99; 95% CI: 1.04, 3.81), diabetes (HR, 2.20; 95% CI: 1.08, 4.49), and first-degree relatives with cancer (HR, 1.70; 95% CI: 1.23, 2.36) were at higher risk of EOCRC. Conclusion: We identified several modifiable as well as nonmodifiable risk factors, such as higher BMI, alcohol and fish consumption, hypertension, and diabetes, were associated with EOCRC.
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BACKGROUND: The purpose of the study was to evaluate whether KRAS mutation could be an independent prognostic biomarker in patients undergoing pulmonary metastasectomy (PM) for colorectal cancer (CRC). METHODS: A systemic review was performed by searching online databases to identify studies reporting overall survival (OS) and recurrence free survival (RFS) of CRC patients undergoing PM. Pooled HRs were calculated for OS and RFS. RESULTS: A total of 15233 patients from 60 studies were included. Pooled analysis showed that KRAS mutation was associated with worse OS (HR: 1.86, 95 % Cl: 1.35-2.57) and RFS (HR: 1.68, 95 % Cl: 1.38-2.04). A significant effect on OS and/or RFS was also shown by other 18 factors. CONCLUSIONS: This meta-analysis found that KRAS mutation is an important prognostic predictor for OS and RFS in CRC patients undergoing PM, supporting a comprehensive model including clinicopathological and biological factors for optimal patients selection and prognosis for surgical treatment.
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Neoplasias Colorretais , Neoplasias Pulmonares , Metastasectomia , Neoplasias Colorretais/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
BACKGROUND AND AIMS: Previous studies have suggested that aggressive hydration with lactated ringer solution are one of the protective factors in preventing post endoscopic retrograde cholangiopancreatography (post-ERCP). We conducted a systematic review and meta-analysis to examine the efficacy aggressive hydration with lactated Ringer solution in preventing PEP. METHODS: All published and unpublished articles on aggressive hydration with lactated ringer solution in those underwent ERCP procedure for any reasons were screened for eligibility. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. This paper doesn't need the IRB approval. RESULTS: Seven RCTs met the inclusion criteria. Meta-analysis indicates that aggressive hydration with lactated Ringer solution were associated with lower PEP rate.[odds ratio (OR) 0.29; 95% confidence interval (CI) 0.18-0.48]; lower incidence of hyperamylasemia (OR 0.49; 95% CI 0.35, 0.69) and lower risk of pain (OR 0.28; 95% CI 0.10-0.81). The association between aggressive hydration with lactated Ringer solution and incidence of moderate severity PEP were unclear (OR 0.57; 95% CI 0.22, 1.45). Sensitivity analyses also showed that omitting 1 study from analysis of PEP rate could reduce the heterogeneity but did not change the conclusion of this meta-analysis. A cumulating meta-analysis was performed statistically which showed a stable result of overall incidence of PEP. CONCLUSIONS: Aggressive hydration with lactated Ringer solution was a protective factor in reducing the overall incidence of PEP, hyperamylasemia and risk of abdominal pain.
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Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/etiologia , Pancreatite/prevenção & controle , Lactato de Ringer/uso terapêutico , Dor Abdominal/etiologia , Dor Abdominal/prevenção & controle , Humanos , Hiperamilassemia/prevenção & controle , Incidência , Razão de Chances , Pancreatite/epidemiologia , Substâncias Protetoras/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We investigated the prognostic significance of Nudix hydrolase 1 (NUDT1) in hepatocellular carcinoma (HCC). NUDT1 mRNA and protein levels were significantly higher in HCC tissues than normal liver tissues. The level of NUDT1 expression correlated with tumor grade, stage, size, differentiation, degree of vascular invasion, overall survival (OS), and disease-free survival (DFS) in HCC patients. Multivariate analysis showed that NUDT1 expression was an independent prognostic factor for OS and DFS in HCC patients. We constructed a prognostic nomogram with NUDT1 expression, AFP levels, vascular invasion, Child-Pugh classification, age, sex, AJCC staging, and tumor differentiation as variables. This nomogram was highly accurate in predicting the 5-year OS of HCC patients (c-index= 0.709; AUC= 0.740). NUDT1 silencing in HCC cells significantly reduced their survival, colony formation, migration, and invasiveness. Gene set enrichment analysis showed that biological pathways related to cell cycle, fatty acid metabolism, bile acid and bile salt metabolism, and PLK1 signaling were associated with NUDT1, as were the gene ontology terms "DNA binding transcription activator activity," "RNA polymerase II," "nuclear division," and "transmembrane transporter activity." Our study thus demonstrates that NUDT1 is a prognostic biomarker with therapeutic potential in HCC patients.
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Carcinoma Hepatocelular/genética , Enzimas Reparadoras do DNA/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Monoéster Fosfórico Hidrolases/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Enzimas Reparadoras do DNA/biossíntese , DNA de Neoplasias/genética , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Monoéster Fosfórico Hidrolases/biossíntese , Prognóstico , Regulação para CimaRESUMO
This study reports the effect of anolytic nitrite concentration on electricity generation and electron transfer in microbial fuel cells (MFCs). Anolytic nitrite enhanced the electricity generation capability of the MFCs at relatively low concentrations (< 60 mg·L-1) but inhibited the activity of anodic electrogenic bacteria at high concentrations. In the anode chamber of the MFC, nitrite was converted to nitrate-releasing electrons before being quickly removed through denitrification. Nitrite alone (in the absence of organic matters) could not perform as an electricity production matrix but promoted electricity production as a co-matrix in the MFC. At an influent nitrite concentration of 60 mg·L-1, the coulombic efficiency of the MFC was minimized at approximately 5.4%, and the charge transfer resistance was also lowest, while the concentrations of extracellular polymeric substances (EPS) and cytochrome c were both maximized. Higher anolytic nitrite concentrations (> 60 mg·L-1) inhibited the production of cytochrome c and EPS and increased the charge transfer resistance, thereby reducing the efficiency of electron transfer in the anodic biofilm. The results provide valuable guidelines for MFC applications in wastewater treatment processes with nitrite-containing influents.
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Fontes de Energia Bioelétrica , Eletricidade , Eletrodos , Elétrons , NitritosRESUMO
In this paper, a novel core-shell structure magnetic microsphere Fe3O4@SiO2-TPM@StVp(Fe3O4@SiO2-3-(trimethoxysilyl)propyl methacrylate@styrene and n-vinylpyrrolidone) was successfully synthesized and used as a magnetic solid-phase extraction adsorbent for extraction of aristolochic acid I (AAI) in traditional Chinese medicine soup. The prepared Fe3O4@SiO2-TPM@StVp was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), vibrating sample magnetometer (VSM) and Fourier-transform infrared spectroscopy (FT-IR). The microspheres have various advantages of excellent hydrophilicity and π-electron system, which is very suitable for determining target analytes followed by high performance liquid chromatography (HPLC). The main factors, including the pH of samples, amount of adsorbent, adsorption time, elution solvent and desorption time, were optimized. Under optimal conditions, the proposed method showed a wide linear range of 0.4-10⯵g/mL and a good correlation coefficient (R2 = 0.9918). The pretreatment procedure was achieved within 10â¯min. The recoveries of aristolochic acid I in real samples range from 80.9% to 89.6% with relative standard deviations less than 4.9%, highlighting the accuracy of this method.
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Ácidos Aristolóquicos/análise , Cromatografia Líquida de Alta Pressão/métodos , Fenômenos Magnéticos , Medicina Tradicional Chinesa , Extração em Fase Sólida/métodos , Adsorção , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Metacrilatos/química , Microesferas , Padrões de Referência , Reprodutibilidade dos Testes , Dióxido de Silício/química , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de TempoRESUMO
The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of ß-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3ß (GSK-3ß) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of ß-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with ß-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3ß/ß-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
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Proliferação de Células/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Glicogênio Sintase Quinase 3 beta/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HT29 , Humanos , Invasividade Neoplásica/patologia , RNA Interferente Pequeno/genética , beta Catenina/genéticaRESUMO
There has been increasing research focusing on the detection and occurrence of wastewater contamination in urban water systems. To find suitable markers to indicate industrial and domestic sewage flows inappropriately entering storm drains, this study investigated the occurrence and fate of 52 chemical markers through wastewater treatment facilities of manufacturers of agricultural and sideline products, beverage products, and pharmaceutical products, which are also consumed in our daily life. Of the 52 candidate markers, sodium, chloride, potassium, isomalto-oligosaccharide, acesulfame, theanine, glycerol, and clarithromycin were found to be conservative markers, with an average change in concentrations through the wastewater treatment processes of <30%. These markers are useful in identifying industrial and domestic sewage flow contamination in urban sewers. Specially, sodium, chloride, potassium, isomalto-oligosaccharide, acesulfame, and clarithromycin exhibited higher concentrations in blackwater than in greywater, with detected average concentrations of 43.8â¯mg/L, 189â¯mg/L, 37.3â¯mg/L, 123⯵g/L, 37.2⯵g/L, and 0.99⯵g/L in blackwater, respectively. In contrast, theanine and glycerol were observed with higher concentrations in greywater than in blackwater (average 10.1⯵g/L and 19.5⯵g/L in greywater, respectively). The benchmark concentrations to discriminate between industrial and domestic sewage were also presented. A study in a storm drainage system of downstream Taihu catchment, China demonstrated the usefulness of the markers as low-cost options to trace and quantify misconnected wastewater entries into storm drains, while denoting priority areas for misconnected entries correction.
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BACKGROUND: Hepatocellular carcinoma is a malignant tumor with a highly invasive and metastatic phenotype, and the detection of potential indicators associated with its recurrence and metastasis after surgical resection is critical for patient survival. METHODS: Transcriptome data for large cohorts (n = 1432) from multicenter sources were comprehensively analyzed to explore such potential signatures. The prognostic value of the selected indicators was investigated and discussed, and a comparison with conventional clinicopathological features was performed. A survival predictive nomogram for 5-year survival was established with the selected indicator using the Cox proportional hazards regression. To validate the indicator at the protein level, we performed immunohistochemical staining with paraffin-embedded slides of hepatocellular carcinoma samples (n = 67 patients) from our hospital. Finally, a gene set enrichment analysis (GSEA) was performed to detect the underlying biological processes and internal mechanisms. RESULTS: The liver-specific protein paraoxonase 1 (PON1) was found to be the most relevant indicator of tumor recurrence, invasiveness, and metastasis in the present study, and the downregulation of PON1 might reveal poor survival for patients with hepatocellular carcinoma. The C-index of the PON1-related nomogram was 0.714, thus indicating a more effective predictive performance than the 7th American Joint Committee on Cancer (AJCC) tumor stage (0.534), AJCC T stage (0.565), or alpha-fetoprotein (0.488). The GSEA revealed that PON1 was associated with several hepatocellular carcinoma-related pathways, including the cell cycle, DNA replication, gap junction and p53 downstream pathways. CONCLUSIONS: The downregulation of paraoxonase 1 may suggest worse outcomes and a higher recurrence rate. Thus, paraoxonase 1 might represent an indicator for predicting the survival of patients with hepatocellular carcinoma.
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Arildialquilfosfatase/metabolismo , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Modelos Biológicos , Recidiva Local de Neoplasia/patologia , Feminino , Humanos , Metástase Neoplásica , Especificidade de Órgãos , Prognóstico , Análise de SobrevidaRESUMO
OBJECTIVES: Accumulating evidence suggests that long non-coding RNA (lncRNA) may affect hepatocellular carcinoma (HCC) progression. However, the mechanism remains unclear. Previous studies have shown that exosomes may promote tumor progression by transporting proteins. Our study aimed to determine the prognostic value of lncRNAs in HCC and the underlying mechanism. METHODS: A dataset comprising a HCC cohort of 364 patients from The Cancer Genome Atlas (TCGA) was analyzed to identify lncRNAs with prognostic value. Co-expression and competing endogenous RNA (ceRNA) networks were constructed to investigate the mechanism of exosome-related lncRNAs. To confirm the bioinformatics analysis results, 95 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH). RESULTS: Five lncRNAs (CTD-2116N20.1, AC012074.2, RP11-538D16.2, LINC00501 and RP11-136I14.5) with significant differences were identified (P<0.001). A prognostic nomogram was constructed with a C-index of 0.701. The co-expression and ceRNA networks showed possible mechanisms for CTD-2116N20.1 and RP11-538D16.2. The CISH results confirmed that CTD-2116N20.1 and RP11-538D16.2 were correlated with a poor prognosis for HCC patients. CONCLUSION: Our findings provide an independent and effective prognostic model to predict the survival rate of HCC patients. RP11-538D16.2 and CTD-2116N20.1 are highlighted as important exosome-related lncRNAs.
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Several microRNAs (miRNAs) have been closely correlated with the development of hepatocellular carcinoma (HCC). However, the involvement of miR-300 in the development of HCC remains unknown. This study elucidated the potential molecular mechanisms of miR-300 in the modulation of the epithelial-mesenchymal transition (EMT) and invasion of HCC. The expression levels of miR-300 in HCC cells and clinical samples were detected by quantitative real-time PCR and in situ hybridization. The in vitro function of miR-300 in HCC was evaluated using a migration/invasion assay. Quantitative real-time PCR, western blotting, immunofluorescence and immunohistochemistry were used to validate the roles of miR-300 and FAK/PI3K/AKT in EMT progression. A dual-luciferase reporter assay was performed to confirm the target gene. miR-300 was down-regulated in HCC and significantly correlated with a poor prognosis in HCC patients. The down-regulation of miR-300 increased the invasiveness of the HCC cells, and promoted the EMT in both HCC tissues and HCC cells. In contrast, up-regulation of miR-300 led to the opposite results. Ectopic overexpression of miR-300 reversed TGF-ß1-induced EMT in SMMC-7721 cells, and according to a dual-luciferase reporter assay and rescue assay, miR-300 inhibits the EMT-mediated migration and invasion of HCC cells via the targeted modulation of FAK and the downstream PI3K/AKT signaling pathway. miR-300 targeting modulates FAK, and the PI3K/AKT signaling pathway inhibits the EMT and suppresses the migration and invasion of HCC cells. Thus, miR-300 represents a promising therapeutic target for HCC.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Modelos de Riscos Proporcionais , Análise de Regressão , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
BACKGROUND: Alpha-fetal protein (AFP) is an important conventional clinical diagnostic indicator of hepatocellular carcinoma (HCC). However, the utilization of AFP alone might yield deceptive results due to its limited sensitivity and accuracy. AIMS: Our study was designed to investigate latent diagnostic biomarkers that could function as auxiliary clinical indicators of HCC and enhance the accuracy of joint diagnosis with AFP. METHODS: We analyzed gene expression profiles and clinical data from HCC patients in The Cancer Genome Atlas database. Differentially expressed genes were identified, and a gene set enrichment analysis was conducted to uncover their biological functions and molecular processes. A weighted correlation network analysis and a protein-protein interaction analysis were performed to detect AFP-related biomarkers. The diagnostic performance of these biomarkers was verified using datasets from the GEO database. A diagnostic nomogram was established using the expression levels of potential biomarkers. Quantitative real-time PCR was performed using tissues from 16 HCC patients to validate the results. RESULTS: Five AFP-related diagnostic biomarkers, CDT1, MCM7, NUDT1, CENPM, and HDAC11, were discovered. The diagnostic performance of these biomarkers and the nomogram were demonstrated to be excellent according to receiver operating characteristic curves. CDT1, MCM7, and NUDT1 were shown to be up-regulated in HCC tissues through quantitative real-time PCR. CONCLUSIONS: We discovered five diagnostic biomarkers and established a nomogram as a complement to AFP in the diagnosis of HCC. Our results provide a more accurate diagnostic plan for HCC patients based on next-generation sequencing compared with AFP alone.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Neoplasias Hepáticas/diagnóstico , Componente 7 do Complexo de Manutenção de Minicromossomo/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , alfa-Fetoproteínas/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/genética , Enzimas Reparadoras do DNA/genética , Feminino , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Componente 7 do Complexo de Manutenção de Minicromossomo/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Monoéster Fosfórico Hidrolases/genética , RNA Mensageiro/metabolismo , Curva ROC , Reação em Cadeia da Polimerase em Tempo RealRESUMO
In this study, a biological denitrifying process using a sequencing batch reactor (SBR) was employed to treat reverse osmosis (RO) concentrate with high conductivity produced from a coking wastewater plant. From the results, the average removal efficiencies for chemical oxygen demand, total nitrogen, and nitrate were 79.5%, 90.5%, and 93.1%, respectively. Different microbial communities were identified after sequencing the V1-V3 region of the 16S rRNA gene using the MiSeq platform, and the major bacterial phyla in the SBR system were Proteobacteria and Bacteroidetes. The main microorganisms responsible for denitrification were from the genera Hyphomicrobium, Thauera, Methyloversatilis, and Rhodobacter. Quantitative real-time PCR was used to quantify the absolute levels of denitrifying genes, including narG, nirS, nirK, and nosZ, during the start-up and stable operation of the SBR. The abundances of narG, nirK, and nosZ were lower during stable operation than those in the start-up period. The abundance of nirS at a concentration of 104-105 copies/ng in DNA was much higher than that of nirK, making it the dominant functional gene responsible for nitrite reduction. The higher nitrate removal efficiency suggests that biological denitrification using SBR is an effective technique for treating RO concentrate produced from coking wastewater plants.
Assuntos
Reatores Biológicos , Coque , Águas Residuárias , Desnitrificação , Osmose , RNA Ribossômico 16S , Microbiologia da ÁguaRESUMO
AT-rich interaction domain 4B (ARID4B), which belongs to the ARID family, is heavily involved in cell growth and differentiation and is closely associated with many types of tumors. However, the role of this protein in hepatocellular carcinoma (HCC) remains unknown. In this study, we used data from The Cancer Genome Atlas and Gene Expression Omnibus to analyze ARID4B expression in HCC. We subjected 15 pairs of fresh-frozen tissue samples to quantitative real-time polymerase chain reaction and Western blotting analyses to investigate ARID4B expression. We also subjected 157 formalin-fixed, paraffin-embedded HCC tissue samples to immunohistochemical analysis to detect ARID4B expression and to determine the clinical significance of ARID4B expression in HCC. The bioinformatics analysis, quantitative real-time polymerase chain reaction, and Western blotting results showed that ARID4B was highly expressed in HCC tissues compared with adjacent normal liver tissues. High ARID4B expression was strongly correlated with tumor number (P = .02), vascular invasion (P = .004), Edmondson-Steiner grades (P = .000), and tumor-node-metastasis stages (P = .001). Moreover, Kaplan-Meier and Cox proportional-hazards analyses indicated that high ARID4B expression was significantly associated with poor survival in patients with HCC and that ARID4B was an independent prognostic factor for overall survival and disease-free survival in patients with HCC. In conclusion, our results suggest that ARID4B acts as an oncogene in HCC and can therefore serve as a biomarker for the prognoses of patients with HCC.