The effects of saturated and unsaturated fatty acids on MASLD: a Mendelian randomization analysis and in vivo experiment.

Background: Excessive intake of fatty acids is a key factor contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of saturated fatty acids (SFA) and unsaturated fatty acids (UFA) on the development of MASLD are uncertain. Therefore, we conducted two-sample Mendelian randomization studies and animal experiments to explore the effects of SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the risk of developing MASLD.

Cross-species variability in lobular geometry and cytochrome P450 hepatic zonation: insights into CYP1A2, CYP2D6, CYP2E1 and CYP3A4.

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry.

Bayesian modelling of time series data (BayModTS)-a FAIR workflow to process sparse and highly variable data.

Motivation: Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such information while consistently handling uncertainties.

Quantifying fat zonation in liver lobules: an integrated multiscale in silico model combining disturbed microperfusion and fat metabolism via a continuum biomechanical bi-scale, tri-phasic approach.

Metabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g.

Normothermic Ex Vivo Liver Machine Perfusion in Mouse.

This protocol presents an optimized erythrocytes-free NEVLP system using mouse livers. Ex vivo preservation of mouse livers was achieved by employing modified cannulas and techniques adapted from conventional commercial ex vivo perfusion equipment. The system was utilized to evaluate the preservation outcomes following 12 h of perfusion.

Periportal steatosis in mice affects distinct parameters of pericentral drug metabolism.

Little is known about the impact of morphological disorders in distinct zones on metabolic zonation. It was described recently that periportal fibrosis did affect the expression of CYP proteins, a set of pericentrally located drug-metabolizing enzymes. Here, we investigated whether periportal steatosis might have a similar effect.

Microbial transformation of some simple isoquinoline and benzylisoquinoline alkaloids and in vitro studies of their metabolites.

Simple isoquinoline alkaloids (heliamine, dehydroheliamine), a phthalide isoquinoline alkaloid noscapine, and an aporphine alkaloid boldine are biosynthetically derived from an amino acid tyrosine. These substrates and a simple synthetic isoquinoline alkaloid (2-acetyl-7-amino-1,2,3,4-tetrahydroisoquinoline) contain an isoquinoline nucleus. The biotransformation of these substrates via reduction, oxidation, hydroxylation, and N-oxidation reactions with different microorganism produced nine metabolites, namely: N-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl) acetamide (Metabolite 1), heliamine N-oxide (Metabolite 2), 6,7-dimethoxyisoquinoline (Metabolite 3), 3,4-dihydro-6,7-dimethoxy isoquinolin-1-one (Metabolite 4), heliamine (Metabolite 5), dehydroheliamine N-oxide (Metabolite 6), cotarnine (Metabolite 7), 5-hydroxy cotarnine (Metabolite 8), and boldine N-oxide (Metabolite 9).

In silico and in vitro studies of isolated constituents from Callistemon citrinus leaves: Anti-microbial potential and inhibition of iNOS activity.

Phytochemical investigation of Callistemon citrinus (Curtis) Skeels (syn. Callistemon lanceolatus (Sm.) Sweet and Melaleuca citrina (Curtis) Dum.

Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a.

The metabolism of papaverine, the opium benzylisoquinoline alkaloid, with Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968 and Cunninghamella echinulate ATCC 1382 has resulted in O-demethylation, O-methylglucosylation and N-oxidation products. Two new metabolites (4″-O-methyl-β-D-glucopyranosyl) 4'-demethyl papaverine and (4″-O-methyl-β-D-glucopyranosyl) 6-demethyl papaverine, (Metabolites 5 and 6) together with 4'-O-demethylated papaverine (Metabolite 1), 3'-O-demethylated papaverine (Metabolite 2), 6-O-demethylated papaverine (Metabolite 3) and papaverine N-oxide (Metabolite 4) were isolated. The structure elucidation of the metabolites was based primarily on 1D, 2D-NMR analyses and HRMS.

Sarcoroseolides A-D, four undescribed cembranoids from the Red Sea soft coral .

Four undescribed cembranoids, sarcoroseolides () along with nine reported related cembranoids () were isolated from the soft coral . The chemical structures of sarcoroseolides - were elucidated by extensive 1 D and 2 D NMR as well as HR-ESIMS spectroscopic data. Moreover, the geometric and absolute configurations were assigned by the modified Mosher's method and/or NOESY experiments.

Roadmap for Quality by Design Implementation for Dietary Supplements.

Background: Recently, there is a growing interest in quality by design (QbD) in the dietary supplements industry.

Objective: Effective QbD implementation necessitates a comprehensive understanding of multiple factors such as; the relationship between the critical qualities attributes (CQAs) and the scientific properties of the dietary supplement, the relationship between the manufacturing process, CQAs and the variability in raw materials. There are still two critical challenging concerns to be addressed in the implementation of QbD for herbal drugs.

Isolation, synthesis, and drug interaction potential of secondary metabolites derived from the leaves of miracle tree (Moringa oleifera) against CYP3A4 and CYP2D6 isozymes.

Background: Moringa oleifera Lam. is known as a drumstick tree that is widely cultivated in various subtropical and tropical provinces. Previous studies indicated that both aqueous and methanolic extracts of M.

Impact of bone marrow-derived mesenchymal stem cells on remodeling the lung injury induced by lipopolysaccharides in mice.

Aim: This study evaluated the potential of bone marrow derived mesenchymal stem cells (MSCs) to regulate cytokines and remodel the lung induced by lipopolysaccharide (LPS; O-antigen).

Materials & Methods: A group of mice (n = 21) was inoculated intraperitoneally with one dose 0.1 ml containing 0.

Computationally assisted assignment of kahalalide Y configuration using an NMR-constrained conformational search.

Assignment of the absolute configuration of cyclic peptides frequently yields challenges, leaving one or more stereogenic centers unassigned due to small quantities of sample and the limited utility of Marfey's or other methods for assigning amino or hydroxy acids. Here, we report isolation of kahalalide Y (1) from Bryopsis pennata for the first time; in addition, the application of a combination of molecular modeling and NOE distance constraint calculations was utilized to determine the conformation of 1 and the absolute configuration of the final stereogenic center of 1. Using the Schrödinger suite, the structure of 1 was sketched in Maestro and minimized using the OPLS2005 force field in Macromodel.