RESUMO
In cis-regulatory elements, enhancers and promoters with complex molecular interactions are used to coordinate gene transcription through physical proximity and chemical modifications. These processes subsequently influence the phenotypic characteristics of an organism. An in-depth exploration of enhancers and promoters can substantially enhance our understanding of gene regulatory networks, shedding new light on mammalian development, evolution and disease pathways. In this review, we provide a comprehensive overview of the intrinsic structural attributes, detection methodologies as well as the operational mechanisms of enhancers and promoters, coupled with the relevant novel and innovative investigative techniques used to explore their actions. We further elucidated the state-of-the-art research on the roles of enhancers and promoters in the realms of mammalian development, evolution and disease, and we conclude with forward-looking insights into prospective research avenues.
Assuntos
Redes Reguladoras de Genes , Mamíferos , Animais , Estudos Prospectivos , Regiões Promotoras Genéticas , Mamíferos/genéticaRESUMO
Parabens are largely concentrated in food waste (FW) due to their large consumption as the widely used preservative. To date, whether and how they affect FW resource recovery via anaerobic fermentation is still largely unknown. This work unveiled the hormesis-like effects of two typical parabens (i.e., methylparaben and n-butylparaben) on VFAs production during FW anaerobic fermentation (i.e., parabens increased VFAs by 6.73-14.49 % at low dose but caused 82.51-87.74 % reduction at high dose). Mechanistic exploration revealed that the parabens facilitated the FW solubilization and enhanced the associated substrates' biodegradability. The low parabens enriched the functional microorganisms (e.g., Firmicutes and Actinobacteria) and upregulated those critical genes involved in VFAs biosynthesis (e.g., GCK and PK) by activating the microbial adaptive capacity (i.e., quorum sensing and two-component system). Consequently, the metabolism rates of fermentation substrates and subsequent VFAs production were accelerated. However, due to increased biotoxicity of high parabens, the functional microorganisms and relevant metabolic activities were depressed, resulting in the significant reduction of VFAs biosynthesis. Structural equation modeling clarified that microbial community was the predominant factor affecting VFAs generation, followed by metabolic pathways. This work elucidated the dose-dependent effects and underlying mechanisms of parabens on FW anaerobic fermentation, providing insights for the effective management of FW resource recovery.
Assuntos
Ácidos Graxos Voláteis , Fermentação , Parabenos , Parabenos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Biodegradação Ambiental , Anaerobiose , Relação Dose-Resposta a Droga , Perda e Desperdício de AlimentosRESUMO
PURPOSE: To analyze the plasma lipid spectrum between healthy control and patients with pancreatic cancer and to select differentially expressed tumor markers for early diagnosis. METHODS: In total, 20 patents were divided into case group and healthy control group according to surgical pathology. Of almost 1206 plasma lipid molecules harvested from 20 patients were measured by HILIC using the normal phase LC/MS. Heat map presented the relative levels of metabolites and lipids in the healthy control group and patients with pancreatic cancer. The PCA model was constructed to find out the difference in lipid metabolites. The principal components were drawn in a score plot and any clustering tendency could be observed. PLS-DA were performed to distinguish the healthy control group and pancreatic cancer according to the identified lipid profiling datasets. The volcano plot was used to visualize all variables with VIP>1 and presented the important variables with P<0.01 and |FC|>2. RESULTS: The upregulated lipid metabolites in patients with pancreatic cancer contained 9 lipids; however, the downregulated lipid metabolites contained 79 lipids. CONCLUSION: There were lipid metabolomic differences in patients with pancreatic cancer, which could serve as potential tumor markers for pancreatic cancer.
Assuntos
Detecção Precoce de Câncer , Lipidômica , Neoplasias Pancreáticas , Biomarcadores , Biomarcadores Tumorais , Humanos , Lipídeos , Metabolômica , Neoplasias Pancreáticas/diagnósticoRESUMO
Abstract Purpose To analyze the plasma lipid spectrum between healthy control and patients with pancreatic cancer and to select differentially expressed tumor markers for early diagnosis. Methods In total, 20 patents were divided into case group and healthy control group according to surgical pathology. Of almost 1206 plasma lipid molecules harvested from 20 patients were measured by HILIC using the normal phase LC/MS. Heat map presented the relative levels of metabolites and lipids in the healthy control group and patients with pancreatic cancer. The PCA model was constructed to find out the difference in lipid metabolites. The principal components were drawn in a score plot and any clustering tendency could be observed. PLS-DA were performed to distinguish the healthy control group and pancreatic cancer according to the identified lipid profiling datasets. The volcano plot was used to visualize all variables with VIP>1 and presented the important variables with P<0.01 and -FC->2. Results The upregulated lipid metabolites in patients with pancreatic cancer contained 9 lipids; however, the downregulated lipid metabolites contained 79 lipids. Conclusion There were lipid metabolomic differences in patients with pancreatic cancer, which could serve as potential tumor markers for pancreatic cancer.