RESUMO
BACKGROUND: Recent studies have demonstrated the relevance of circulating factors in the occurrence and development of colorectal cancer (CRC); however, the causal relationship remains unclear. METHODS: Summary-level data for CRC were obtained from the UK Biobank (5,657 cases and 372,016 controls), FinnGen cohort (3,022 cases and 215,770 controls), and BioBank Japan Project (BBJ, 7,062 cases and 195,745 controls). Thirty-two peripheral markers with consistent definitions were collected from the three biobanks. Mendelian randomization (MR) was used to evaluate the causal effect of circulating factors on CRC. The effects from the three consortiums were combined using trans-ancestry meta-analysis methods. RESULTS: Our analysis provided compelling evidence for the causal association of higher genetically predicted eosinophil cell count (EOS, odds ratio [OR], 0.8639; 95% confidence interval [CI] 0.7922-0.9421) and red cell distribution width (RDW, OR, 0.9981; 95% CI, 0.9972-0.9989) levels with a decreased risk of CRC. Additionally, we found suggestive evidence indicating that higher levels of total cholesterol (TC, OR, 1.0022; 95% CI, 1.0002-1.0042) may increase the risk of CRC. Conversely, higher levels of platelet count (PLT, OR, 0.9984; 95% CI, 0.9972-0.9996), total protein (TP, OR, 0.9445; 95% CI, 0.9037-0.9872), and C-reactive protein (CRP, OR, 0.9991; 95% CI, 0.9983-0.9999) may confer a protective effect against CRC. Moreover, we identified six ancestry-specific causal factors, indicating the necessity of considering patients' ancestry backgrounds before formulating prevention strategies. CONCLUSIONS: MR findings support the independent causal roles of circulating factors in CRC, which might provide a deeper insight into early detection of CRC and supply potential preventative strategies.
Assuntos
Neoplasias Colorretais , Análise da Randomização Mendeliana , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Masculino , Feminino , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Japão/epidemiologia , Fatores de RiscoRESUMO
Enzyme-catalyzed CO2 reduction to value-added commodities is important for alleviating the global environmental issues and energy crises due to high selectivity and mild conditions. Owing to high energy density, formic acid or methanol produced from CO2 using formate dehydrogenase (FDH) or multi-enzyme cascades are promising target chemicals for CO2 utilization. However, the low activity, poor stability and low reusability of key enzymes involved in such process hampered its large-scale application. Enzyme immobilization provides an effective solution to these problems and significant progress have been made in immobilization carriers. Moreover, integration of enzyme immobilization with other catalysis techniques have been explored extensively. This review summarized the recent advances in the immobilization of enzymes using membranes, inorganic materials, metal-organic frameworks, covalent organic frameworks and other carriers, and illustrated the characteristics and advantages of different immobilization materials and immobilization methods. The synergistic effects and applications of immobilized enzymes and electrocatalytic or photocatalytic coupling reaction systems for CO2 reduction were further summarized. Finally, the current challenges of enzyme immobilization technology and coupling reaction systems were pointed out and their development prospects were presented.
Assuntos
Enzimas Imobilizadas , Estruturas Metalorgânicas , Dióxido de Carbono , Catálise , Formiato DesidrogenasesRESUMO
Activation and turning CO2 into value added products is a promising orientation to address environmental issues caused by CO2 emission. Currently, electrocatalysis has a potent well-established role for CO2 reduction with fast electron transfer rate; but it is challenged by the poor selectivity and low faradic efficiency. On the other side, biocatalysis, including enzymes and microbes, has been also employed for CO2 conversion to target Cn products with remarkably high selectivity; however, low solubility of CO2 in the liquid reaction phase seriously affects the catalytic efficiency. Therefore, a new synergistic role in bioelectrocatalysis for CO2 reduction is emerging thanks to its outstanding selectivity, high faradic efficiency, and desirable valuable Cn products under mild condition that are surveyed in this review. Herein, we comprehensively discuss the results already obtained for the integration craft of enzymatic-electrocatalysis and microbial-electrocatalysis technologies. In addition, the intrinsic nature of the combination is highly dependent on the electron transfer. Thus, both direct electron transfer and mediated electron transfer routes are modeled and concluded. We also explore the biocompatibility and synergistic effects of electrode materials, which emerge in combination with tuned enzymes and microbes to improve catalytic performance. The system by integrating solar energy driven photo-electrochemical technics with bio-catalysis is further discussed. We finally highlight the significant findings and perspectives that have provided strong foundations for the remarkable development of green and sustainable bioelectrocatalysis for CO2 reduction, and that offer a blueprint for Cn valuable products originate from CO2 under efficient and mild conditions.
Assuntos
Dióxido de Carbono , Técnicas Eletroquímicas , Transporte de Elétrons , Biocatálise , CatáliseRESUMO
Background: Colorectal cancer (CRC) is one of the most common digestive system tumors worldwide. Hypoxia and immunity are closely related in CRC; however, the role of hypoxia-immune-related lncRNAs in CRC prognosis is unknown. Methods: Data used in the current study were sourced from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases. CRC patients were divided into low- and high-hypoxia groups using the single-sample gene set enrichment analysis (ssGSEA) algorithm and into low- and high-immune groups using the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm. Differentially expressed lncRNAs (DElncRNAs) between low- and high-hypoxia groups, low- and high-immune groups, and tumor and control samples were identified using the limma package. Hypoxia-immune-related lncRNAs were obtained by intersecting these DElncRNAs. A hypoxia-immune-related lncRNA risk signature was developed using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. The tumor microenvironments in the low- and high-risk groups were evaluated using ssGSEA, ESTIMATE, and the expression of immune checkpoints. The therapeutic response in the two groups was assessed using TIDE, IPS, and IC50. A ceRNA network based on signature lncRNAs was constructed. Finally, we used RT-qPCR to verify the expression of hypoxia-immune-related lncRNA signatures in normal and cancer tissues. Results: Using differential expression analysis, and univariate Cox and LASSO regression analyses, ZNF667-AS1, LINC01354, LINC00996, DANCR, CECR7, and LINC01116 were selected to construct a hypoxia-immune-related lncRNA signature. The performance of the risk signature in predicting CRC prognosis was validated in internal and external datasets, as evidenced by receiver operating characteristic curves. In addition, we observed significant differences in the tumor microenvironment and immunotherapy response between low- and high-risk groups and constructed a CECR7-miRNA-mRNA regulatory network in CRC. Furthermore, RT-qPCR results confirmed that the expression patterns of the six lncRNA signatures were consistent with those in TCGA-CRC cohort. Conclusion: Our study identified six hypoxia-immune-related lncRNAs for predicting CRC survival and sensitivity to immunotherapy. These findings may enrich our understanding of CRC and help improve CRC treatment. However, large-scale long-term follow-up studies are required for verification.
Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/genética , Imunoterapia , Estimativa de Kaplan-Meier , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Microambiente Tumoral/genéticaRESUMO
Gastric cancer is a malignant tumor with a high degree of malignancy. Multiple liver metastases from gastric cancer (LMGCs) are common. However, the treatment of LMGCs is very difficult. It is rare to achieve complete remission (CR) and long-term survival after treatment. We present the case of a patient with gastric adenocarcinoma and multiple liver metastases who showed CR for more than 33 months after perioperative EOX (epirubicin, oxaliplatin, and capecitabine) combination chemotherapy with radical distal gastrectomy and resection of liver metastases. The patient is still in follow-up without tumor recurrence. These findings suggest that LMGC does not necessarily mean a poor prognosis; preoperative chemotherapy combined with surgery may be a good treatment option for LMGC in selected patients. Further studies are needed to support this treatment approach.