Metabolic associated fatty liver disease (MAFLD) is a new concept where the presence of both fatty liver and metabolic abnormality are necessary for diagnosis. Several studies have reported that altered gut microbiome is closely associated with metabolic diseases and non-alcoholic fatty liver disease. However, the studies on MAFLD population are scarce. This prospective study aimed to identify differences in gut microbiome between patients with MAFLD and healthy controls in Korean population. In this study, patients with MAFLD and age, sex-matched healthy controls were included, and their stool samples were collected. Taxonomic composition of gut microbiota was analyzed using 16S ribosomal ribonucleic acid pyrosequencing. Twenty-two MAFLD patients and 44 healthy controls were included. Taxonomic diversity was lower in patients with MAFLD in the aspect of alpha and beta diversity. The differences were also found at phylum, class, family, and genus levels between the two groups. Phylum Proteobacteria, family Enterobactereriaceae, genus Citrobacter abundance was significantly increased and genus Faecalibacterium was significantly decreased in patients with MAFLD. In addition, butyrate-producing bacteria were decreased and ethanol-producing bacteria were increased in patients with MAFLD. The composition of gut microbiome was different between MAFLD and healthy controls in Korean population. This could offer potential targets for therapeutic intervention in MAFLD.
This article deals with the relation between subcategorization and the notion head in OE [P-V] compounds. Many morphosyntactic properties such as category and morphological class percolate from the head to the mother. Subcategorization, however, can percolate to the mother from a nonhead as well as from the head. This is evident from the comparison of their case government properties. This paper shows that the process of developed within Head-driven Phrase Structure Grammar permits a straightforward account of this phenomenon.
c-Met, as a receptor expressed on the cell membrane, contributes to the growth and metastasis of tumors, as well as angiogenesis, mainly through the hepatocyte growth factor (HGF)/c-Met axis during tumor progression. Although several c-Met inhibitors, including small molecules and monoclonal antibody inhibitors, are currently being investigated, their clinical outcomes have not been promising. Development of an antibody–drug conjugate (ADC) against c-Met could be an attractive therapeutic strategy that would provide superior antitumor efficacy with broad-spectrum c-Met expression levels. In the present study, site-specific drug–conjugate technology was applied to develop an ADC using the human-mouse cross-reactive c-Met antibody and a prodrug pyrrolobenzodiazepine (PBD). The toxin payload was uniformly conjugated to the light-chain C-terminus of the native cIRCR201 antibody (drug-to-antibody ratio = 2), as confirmed using LC–MS. Using a high-throughput screening system, we found that cIRCR201-dPBD exhibited varying sensitivities depending on the expression levels of c-Met, and it induced receptor-mediated endocytosis and toxin-mediated apoptosis in 47 different cancer cell lines. cIRCR201-dPBD also showed significant antitumor activity on the MET -amplified cancer cells using in vivo xenograft models. Therefore, cIRCR201-dPBD could be a promising therapeutic strategy for tumors with c-Met expression.
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