Mice fed a high-fat diet for 12 weeks or longer develop hyperglycemia, insulin resistance, dyslipidemia, and fatty liver. Additionally, a high-fat diet induces inflammation that remodels and affects the anti-inflammatory and antiatherogenic property of the high-density lipoprotein (HDL). However, the precise time course of metabolic disease progression and HDL remodeling remains unclear. Short-term (four weeks) high-fat feeding (60% fat calories) was performed in wild-type male C57BL/6J mice to gain insights into the early metabolic disease processes in conjunction with a HDL proteome dynamics analysis using a heavy water metabolic labeling approach. The high-fat diet-fed mice developed hyperglycemia, impaired glucose tolerance, hypercholesterolemia without hypertriglyceridemia or hepatic steatosis. A plasma HDL proteome dynamics analysis revealed increased turnover rates (and reduced half-lives) of several acute-phase response proteins involved in innate immunity, including complement C3 (12.77 ± 0.81 vs. 9.98 ± 1.20 h, p < 0.005), complement factor B (12.71 ± 1.01 vs. 10.85 ± 1.04 h, p < 0.05), complement Factor H (19.60 ± 1.84 vs. 16.80 ± 1.58 h, p < 0.05), and complement factor I (25.25 ± 1.29 vs. 19.88 ± 1.50 h, p < 0.005). Our findings suggest that an early immune response-induced inflammatory remodeling of the plasma HDL proteome precedes the diet-induced steatosis and dyslipidemia.

Post-translational acetylation of proteins by acetyl-CoA is a crucial regulator of proteostasis and substrate metabolism. Ethanol metabolism in the liver induces protein accumulation, acetylation and metabolic disruption. While acetylation impacts enzyme activity and stability, its role in ethanol-related protein accumulation and metabolic dysfunction remains unclear. Using stable isotope-based proteomics, acetylomics, and metabolic profiling in a mouse model of chronic ethanol-induced liver injury, we demonstrate that ethanol induces hepatic steatosis, inflammation, oxidative stress, and proteinopathy linked to altered protein turnover. Ethanol increased the cytosolic protein turnover related to oxidative stress and detoxification, while reducing turnover of mitochondrial metabolic enzymes. It also elevated the acetylation of mitochondrial enzymes and nuclear histones with minimal cytosolic changes, impairing mitochondrial protein degradation. These changes were associated with altered levels of acyl-CoAs and acyl-carnitines, amino acids, and tricarboxylic acid (TCA) cycle intermediates, reflecting impaired fatty acid oxidation, nitrogen disposal and TCA cycle activities. These results suggest that ethanol-induced acetylation contributes to liver injury and that targeting acetylation may offer treatment for alcohol-induced liver diseases.

This study describes the synthesis of a 40-membered macroheterocycle, promising PBP-2a non-β-lactam. The MIC of MHC3@Fe ₃ O ₄ towards S. aureus is ≤0.5 μg mL ⁻¹ and in silico studies showed the high affinity of MHC3 to the allosteric site of PBP-2a.

Deletion of the nuclear hormone receptor small heterodimer partner (Shp) ameliorates the development of obesity and nonalcoholic steatohepatitis (NASH) in mice. Liver-specific SHP plays a significant role in this amelioration. The gut microbiota has been associated with these metabolic disorders, and the interplay between bile acids (BAs) and gut microbiota contributes to various metabolic disorders. Since hepatic SHP is recognized as a critical regulator in BA synthesis, we assessed the involvement of gut microbiota in the antiobesity and anti-NASH phenotype of Shp^-/- mice. Shp deletion significantly altered the levels of a few conjugated BAs. Sequencing the 16S rRNA gene in fecal samples collected from separately housed mice revealed apparent dysbiosis in Shp^-/- mice. Cohousing Shp^-/- mice with WT mice during a Western diet regimen impaired their metabolic improvement and effectively disrupted their distinctive microbiome structure, which became indistinguishable from that of WT mice. While the Western diet challenge significantly increased lipopolysaccharide and phenylacetic acid (PAA) levels in the blood of WT mice, their levels were not increased in Shp^-/- mice. PAA was strongly associated with hepatic peroxisome proliferator-activated receptor gamma isoform 2 (Pparg2) activation in mice, which may represent the basis of the molecular mechanism underlying the association of gut bacteria and hepatic steatosis. Shp deletion reshapes the gut microbiota possibly by altering BAs. While lipopolysaccharide and PAA are the major driving forces derived from gut microbiota for NASH development, Shp deletion decreases these signaling molecules via dysbiosis, thereby partially protecting mice from diet-induced metabolic disorders.

Objective: Lung cancer is one of the most common cancers in the world. It is known that angiogenesis plays a role in the development and metastasis of lung cancer. The anticancer properties of azomethine derivatives known as Schiff bases have been demonstrated. In this study, we aimed to determine the anticancer activity of the newly synthesized azomethine derivative compound B-47/2 on lung cancer and to determine the effect of this component on VEGFB gene expression. Material and Method: Compound B-47/2 was synthesized for the first time. B-47/2 compound was applied to lung cancer cell line A549 at varying concentrations (1-100 µg/mL) and its anticancer activity was found after 24, 48 and 72 incubations using the MTT method. The IC50 dose of B-47/2 was applied to the cells and RNA isolation followed by cDNA synthesis was performed. Then, RT-PCR method was used to determine the expression level of VEGF gene. Results: As a result, it was determined that the B-47/2 compound applied to the A-549 cell line showed the highest cytotoxic activity after 72 hours of incubation. In addition, it was determined that the B-47/2 compound decreased the expression of the VEGFB gene. Discussion: There are studies in which the anticancer activity of azomethine derivatives has been observed. The topic of synthesizing new drugs to prevent cancer is popular. We suggested that the newly synthesized component may have anticancer activity and may be effective on angiogenesis.

Dysregulated histone acetylation links cellular metabolism to gene expression, but measuring its in vivo turnover remains technically challenging. Here, we introduce a ² H2O -based metabolic labeling method coupled with high-resolution Orbitrap mass spectrometry to quantify in vivo histone acetylation dynamics. The approach leverages differing deuterium incorporation rates between fast-labeling acetyl groups and slow-labeling peptide backbones. A two-tier analytical workflow uses full-scan mass spectrometry for mono-acetylated peptides, combined with parallel reaction monitoring (PRM) to resolve site-specific turnover and stoichiometry. Furthermore, monitoring acetyl-group plateau ² H enrichment enables the evaluation of specific substrate contributions to the acetyl-CoA pool supporting histone acetylation. To demonstrate biological utility, we applied this approach to mice maintained on a high-carbohydrate diet or subjected to 48-h fasting to assess nutrient-dependent histone acetylation dynamics. Acetyl-group labeling reflected the metabolic origin of acetyl-CoA, showing greater ² H enrichment in the fed state and reduced enrichment during fasting due to increased utilization of unlabeled fatty acid–derived acetyl-CoA. Fasting accelerated acetylation turnover across multiple histone sites and reduced overall acetylation stoichiometry. Quantitative tracing revealed that fatty acid oxidation becomes an important contributor to histone acetylation during fasting, whereas glucose remains the predominant source of nucleo-cytosolic acetyl-CoA (supplying > 60% of acetylation used carbon). This approach enables simultaneous in vivo assessment of histone acetylation turnover, site occupancy, and acetyl-CoA substrate utilization, offering a robust platform to investigate metabolic-epigenetic crosstalk in health and disease.