RESUMO
Dendrobium huoshanense is an important Traditional Chinese medicine that thickens the stomach and intestines. Its active ingredient Dendrobium huoshanense polysaccharide (DHP), was revealed to relieve the symptoms of liver injury. However, its mechanism of action remains poorly understood. This study aimed to investigate the mechanism of DHP in protecting the liver. The effects of DHP on lipid levels, liver function, and intestinal barrier function were investigated in mice with high-fat diet-induced liver damage. Changes in the gut flora and their metabolites were analyzed using 16S rRNA sequencing and metabolomics. The results showed that DHP reduced lipid levels, liver injury, and intestinal permeability. DHP altered the intestinal flora structure and increased the relative abundance of Bifidobacterium animalis and Clostridium disporicum. Furthermore, fecal metabolomics revealed that DHP altered fecal metabolites and significantly increased levels of gut-derived metabolites, spermidine, and indole, which have been reported to inhibit liver injury and improve lipid metabolism and the intestinal barrier. Correlation analysis showed that spermidine and indole levels were significantly negatively correlated with liver injury-related parameters and positively correlated with the intestinal species B. animalis enriched by DHP. Overall, this study confirmed that DHP prevented liver injury by regulating intestinal microbiota dysbiosis and fecal metabolites.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Dendrobium , Animais , Camundongos , Dendrobium/química , Dieta Hiperlipídica/efeitos adversos , RNA Ribossômico 16S , Espermidina , Polissacarídeos/farmacologia , Polissacarídeos/química , Indóis , LipídeosRESUMO
OBJECTIVE: To produce high concentrations of hyperoside from quercetin using recombinant Escherichia coli with in situ regeneration of UDP-galactose. RESULTS: Sucrose synthase from Glycine max (GmSUS) was co-expressed with UDP-glucose epimerase from E. coli (GalE) in E. coli for regenerating UDP-galactose from UDP and sucrose. Glycosyltransferase from Petunia hybrida (PhUGT) was introduced to synthesize hyperoside from quercetin through the regeneration system of UDP-galactose. Co-expressing with molecular chaperones GroEL/ES successfully enhanced the catalytic efficiency of the recombinant strain, which assisted the soluble expression of PhUGT. By using a fed-batch approach, the production of hyperoside reached 863.7 mg L-1 with a corresponding molar conversion of 93.6% and a specific productivity of 72.5 mg L-1 h-1. CONCLUSION: The method described herein for hyperoside production can be widely applied for the synthesis of isorhamnetin-3-O-galactoside, kaempferol-3-O-galactoside and other flavonoids.
Assuntos
Escherichia coli , Quercetina , Escherichia coli/genética , Escherichia coli/metabolismo , Galactose/metabolismo , Quercetina/análogos & derivados , Quercetina/metabolismo , Difosfato de Uridina/metabolismoRESUMO
The gut microbiota is crucial in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the metabolism of T2DM patients is not well-understood. We aimed to identify the differences on composition and function of gut microbiota between T2DM patients with obesity and healthy people. In this study, 6 T2DM patients with obesity and 6 healthy volunteers were recruited, and metagenomic approach and bioinformatics analysis methods were used to understand the composition of the gut microbiota and the metabolic network. We found a decrease in the abundance of Firmicutes, Oribacterium, and Paenibacillus; this may be attributed to a possible mechanism and biological basis of T2DM; moreover, we identified three critical bacterial taxa, Bacteroides plebeius, Phascolarctobacterium sp. CAG207, and the order Acidaminococcales that can potentially be used for T2DM treatment. We also revealed the composition of the microbiota through functional annotation based on multiple databases and found that carbohydrate metabolism contributed greatly to the pathogenesis of T2DM. This study helps in elucidating the different metabolic roles of microbes in T2DM patients with obesity.
Assuntos
Bactérias/classificação , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Metagenoma , Obesidade/microbiologia , Adulto , Bactérias/metabolismo , Biologia Computacional , Diabetes Mellitus Tipo 2/fisiopatologia , Fezes/microbiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Metagenômica , Pessoa de Meia-IdadeRESUMO
Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE-/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor α (LXRα). Furthermore, inhibition of LXRα can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.
Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Aterosclerose/metabolismo , Colestenonas/farmacologia , Jejuno/efeitos dos fármacos , Lipoproteínas/efeitos dos fármacos , Placa Aterosclerótica/metabolismo , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Aterosclerose/patologia , Células CACO-2 , Colesterol/metabolismo , Ésteres do Colesterol/metabolismo , Dieta Hiperlipídica , Feminino , Glicerofosfolipídeos/metabolismo , Humanos , Jejuno/metabolismo , Jejuno/patologia , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas/metabolismo , Receptores X do Fígado/efeitos dos fármacos , Receptores X do Fígado/metabolismo , Camundongos , Camundongos Knockout para ApoE , Ovariectomia , Placa Aterosclerótica/patologia , Esterol O-Aciltransferase/efeitos dos fármacos , Esterol O-Aciltransferase/metabolismo , Triglicerídeos/metabolismo , Esterol O-Aciltransferase 2RESUMO
MicroRNAs (miRNAs) are involved in the development of several types of tumor; however, their role in spinal gliomas remains unknown. The present study aimed to identify potentially novel spinal cord gliomas (SCG)-associated miRNAs and to characterize their roles in the development and progression of SCG. miRNA expression levels in low-grade SCG (classed as stage I-II SCG based on the World Health Organization grading system), high-grade SCG (classed as stage IV SCG based on the World Health Organization grading system) and 5 control cases were measured using a miRNA expression microarray. Subsequently, blood samples from the spinal cord of patients with differing grades of SCG were screened for differentially expressed miRNAs (DEmiRNAs). Compared with the control group, 7 upregulated and 36 downregulated miRNAs were identified in the low-grade SCG group and a total of 70 upregulated and 20 downregulated miRNAs were identified in the high-grade SCG group (P≤0.05, fold change >2). Gene Ontology analysis revealed that the regulation of cellular metabolic processes, negative regulation of biological processes and axon guidance were primarily involved. Moreover, pathway analysis showed that the target genes of DEmiRNAs were enriched in tumor-related signaling pathways, such as the MAPK and Wnt signaling pathway. The results suggest that DEmiRNAs in peripheral blood may serve as novel target markers with high specificity and sensitivity for the diagnosis of SCG.
RESUMO
In order to study the molecular differences between type 2 diabetes mellitus (T2DM) and T2DM with depression (DD), we aimed to screen the differential expression of lncRNA, mRNA, and circRNA in the blood of patients with T2DM and DD. Based on the self-rating depression scale (SDS), patient health questionnaire 9 (PHQ9), blood glucose and HbA1c, we divided the patients into T2DM and DD group. Peripheral blood was collected from the two groups of patients to perform lncRNA, mRNA, and circRNA expression profiling and screening DD-related specific molecules. Subsequently, bioinformatics analysis was performed to investigate the functions of differentially expressed genes (DEgenes). Finally, RT-PCR and lncRNA-mRNA regulatory network was performed to verify the expressions of lncRNAs and mRNAs related to the occurrence and development of DD. 28 lncRNAs, 107 circRNAs, and 89 mRNAs were identified in DD differential expression profiles. GO and pathway analysis found that 20 biological process (BP) related entities and 20 pathways associated with DD. The analysis shows that the genes that are differentially expressed in the DD group involved in the development of the neuropsychiatric system, immunity, and inflammation. Then, we screening for the important DElncRNA and mRNA associated with DD were verified by RT-PCR experiments and the results of RT-PCR were consistent with the sequencing results. LncRNA, circRNA, and mRNA differential expression profiles exist in DD patients compared with T2DM. The lncRNA-mRNA regulatory network analysis confirmed the crosslinking and complex regulation patterns of lncRNA and mRNA expression and verified the authenticity of the regulatory network.
Assuntos
Depressão/genética , Diabetes Mellitus Tipo 2/genética , Redes Reguladoras de Genes , RNA não Traduzido/genética , Idoso , Depressão/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/metabolismo , TranscriptomaRESUMO
This paper has introduced the terms, concept and characteristics of superfine comminution of traditional Chinese medicine. The progress in the study on the superfine comminution of the single drug and compound prescription was analyzed, and work principles of equipment in common use for superfine comminution were outlined. The future application of superfine comminution technique in traditional Chinese medicine was forecast and the problems that should be solved during the future research work were also pointed out in the paper.