RESUMO
A combination of polysaccharides and tea polyphenols can enhance immune activity synergistically, depending on the type and structure of polysaccharides, but the mechanism remains unknown. This study is aimed to investigate the regulating effects of different seaweed polysaccharide (ι-carrageenan, agarose) and tea polyphenol blends on intestinal flora and intestinal inflammation using an in vitro ascending-transverse-descending colon fermentation system and RAW264.7 cell model. The results showed that seaweed polysaccharides in the presence of tea polyphenol were almost completely degraded at transverse colon fermentation for 36 h. Agarose significantly enhanced the butyric acid production content by increasing the abundance of Lachnospiraceae, whereas agarose and tea polyphenol blends did not have a synergistic effect. On the contrary, ι-carrageenan and tea polyphenol blends synergistically increased the abundance of beneficial bacteria (e.g., Bacteroidetes and Bifidobacterium) and promoted the production of short-chain fatty acids (SCFAs), such as isobutyric acid. Such changes tended to alter the impacts of different seaweed polysaccharides and tea polyphenol blends on intestinal inflammation. Among them, ι-carrageenan and tea polyphenol blends were the most effective in inhibiting lipopolysaccharide-induced NO, ROS, IL-6, and TNF-α production in RAW264.7 cells, indicating the alleviated intestinal inflammation. The results suggest that the seaweed polysaccharide and tea polyphenol blends have prebiotic potential and can benefit intestinal health.
Assuntos
Microbioma Gastrointestinal , Alga Marinha , Humanos , Alga Marinha/metabolismo , Fermentação , Carragenina , Sefarose , Polifenóis/farmacologia , Polissacarídeos/farmacologia , Chá/química , InflamaçãoRESUMO
The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including ß-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of ß-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that ß-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord. IMPORTANCE FMT treatment shows a profound impact on the microenvironment that involves microcirculation, blood-spinal cord-barrier, activation of immune cells, and secretion of neurotrophic factors. Analysis of metabolic profiles reveals around 22 differentially detected metabolites between the groups, and ß-alanine was further chosen for functional validation experiments. Supplementation of SCI mice with ß-alanine significantly improves neuronal survival, and the integrity of blood-spinal cord-barrier at the lesion site, suggesting that ß-alanine might be one of the mediators following FMT that has contributed to the recovery.
Assuntos
Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Animais , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Inflamação/patologia , Camundongos , Fatores de Crescimento Neural , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , beta-AlaninaRESUMO
A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the "SE active core TFs analysis" and "TF enrichment analysis" tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.
RESUMO
Alginate is a natural polysaccharide resource abundant in brown algae and it can be cleaved into alginate oligosaccharides by alginate lyase. Alginate lyases and the bioactive alginate oligosaccharides have been applied in diverse fields such as pharmaceutical therapy and nutraceutical supplementation. Immobilized enzymes greatly facilitate their industrial application owing to their reusability, stability, and tunability. In this study, magnetic Fe3O4 nanoparticles were synthesized and used to immobilize an exolytic alginate lyase AlgL17 that was characterized previously. The immobilized AlgL17 demonstrated enhanced thermal and pH tolerance, extended storage stability, and moderate reusability. The mass spectrum indicated the specific activity of the immobilized AlgL17 to release alginate oligosaccharides (AOS) from alginate polysaccharide. The produced AOS exhibited their antioxidant and antiapoptotic activities in H2O2-stressed human umbilical vein endothelial cells by upregulation of reactive oxygen species scavenging activities and attenuation of the caspase-mediated apoptosis pathway.
Assuntos
Alginatos/metabolismo , Alginatos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeo-Liases/metabolismo , Alginatos/química , Apoptose/efeitos dos fármacos , Biocatálise , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/ultraestrutura , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas de Magnetita/ultraestrutura , Espectrometria de Massas , Microscopia Eletrônica de Varredura , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Oligossacarídeos/farmacologia , Polissacarídeo-Liases/ultraestrutura , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Ultrasound pretreatment is a potent step to disintegrate primary sludge (PS). The supernatant of sonicated PS is recycled as an alternative carbon source for biological phosphorus removal. In this study, we investigated the role of temperature on PS disintegration during sonication. We found that a temperature of 60°C yielded a dissolution rate of about 2% soluble chemical oxygen demand (SCOD) as compared to 7% SCOD using sonication at the specific energy (SE) of 7359kJ/kg TS. Using the SE of 6000kJ/kg TS with heat insulation during sonication, the SCOD dissolution rate of PS was similar to the result at the SE of 7051kJ/kg TS without heat insulation. Upon treatment with sonication, the PS released low concentrations of Cu and Zn into the supernatant. The phosphorus-accumulating organisms (PAOs) used the supernatant of sonicated PS as the carbon source. Supplementation with the diluted sonicated PS supernatant (SCOD≈1000mg/L) in anaerobic phase resulted in the release of phosphorus (36mg/L) and the production of polyhydroxyalkanoates (PHAs) (0.36g PHA/g SS). Compared with sodium acetate, higher polyhydroxyvalerate (PHV) faction in the polyhydroxyalkanoates (PHAs) was observed in the biomass when incubated with sonicated PS as the carbon source. This work provides a simple pathway to conserve energy and to enhance efficiencies of ultrasonic pretreatment and the recovery of carbon source from the sludge for improving the phosphorus removal in the ENR system.