Complementing our earlier syntheses of the gentamicins B1, C1a, C2b, and X2, we describe the synthesis of gentamicins C1, C2, and C2a characterized by methyl substitution at the 6'-position, and so present an alternative access to previous chromatographic methods for accessing these sought-after compounds. We describe the antiribosomal activity of our full set of synthetic gentamicin congeners against bacterial ribosomes and hybrid ribosomes carrying the decoding A site of the human mitochondrial, A1555G mutant mitochondrial, and cytoplasmic ribosomes and establish structure-activity relationships with the substitution pattern around ring I to antiribosomal activity, antibacterial resistance due to the presence of aminoglycoside acetyl transferases acting on the 6'-position in ring I, and literature cochlear toxicity data.
View Article and Find Full Text PDFHepatoid adenocarcinoma of the stomach is a rare histologic subtype of gastric carcinoma. Morphologically, it shows hepatocyte-like features and the tumor cells can show the expression of alpha-fetoprotein (AFP) in the tumor cells as well as in serum. There are a few AFP-negative hepatoid adenocarcinoma tumors that have been reported in the literature.
View Article and Find Full Text PDFBackground & Aims: Necroptosis is a highly inflammatory mode of cell death that has been implicated in causing hepatic injury including steatohepatitis/ nonalcoholic steatohepatitis (NASH); however, the evidence supporting these claims has been controversial. A comprehensive, fundamental understanding of cell death pathways involved in liver disease critically underpins rational strategies for therapeutic intervention. We sought to define the role and relevance of necroptosis in liver pathology.
View Article and Find Full Text PDFGut-brain axis (GBA) communication relies on serotonin (5-HT) signaling between the gut epithelium and the peripheral nervous system, where 5-HT release patterns from the basolateral (i.e., bottom) side of the epithelium activate nerve afferents.
View Article and Find Full Text PDFWe describe the preparation of methyl 5α-methyl-α-d-glucopyranoside and of 5α-fluoro-β-d-glucopyranose per acetate and the NMR-based conformational analysis of their side chains. Both the 5α-methyl and 5α-fluoro substituents increase the population of the gauche,gauche side chain conformer to the extent that it becomes the predominant conformation. In the 5α-methyl series this is attributed to steric effects, whereas in the 5α-fluoro series the optimization of attractive gauche effects is the more likely reason.
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