FBP1/HIF-1α Axis mediates macrophage metabolic reprogramming and serves as diagnostic biomarkers in atherosclerosis.

Temozolomide (TMZ) is a frontline chemotherapeutic agent for glioblastoma multiforme (GBM); however, approximately half of patients develop resistance to therapy. This study investigates the role of altered cellular bioenergetics and metabolism in the acquired TMZ resistance. Using untargeted metabolomics, we explored the metabolic rewiring in TMZ-resistant GBM cells and identified key alterations in glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, and amino acid metabolism, all might be linked to cellular proliferation. Our findings suggest that while glycolysis remains important, increased TCA cycle activity contributes to the drug resistance, supported by increased levels of mitochondrial mass and mitochondrial membrane potential. We observed significantly elevated glutamine levels, which may enhance mitochondrial activity, thereby supporting increased energy production. Furthermore, resistant cells exhibited enhanced NRF2 level in parallel with higher levels of antioxidants, including glutathione and catalase enzyme, and a concomitant decrease in the level of its negative regulator, KEAP1. These factors collectively may contribute to drug resistance by mitigating oxidative stress. These findings indicate that mitochondrial metabolic reprogramming and NRF2/KEAP1-mediated antioxidant defense mechanisms play a crucial role in TMZ resistance, and targeting these pathways may offer a novel strategy to overcome resistance in GBM therapy.

The aim of this study is to elucidate the effects and mechanism of narirutin (NR) in colorectal cancer (CRC). Flow cytometry, xenograft model, cell counting kit-8, colony formation, wound healing, and Transwell assays were performed to assess NR's effects on CRC prevention. Lipid accumulation, triacylglycerol, total cholesterol, and free fatty acids were measured to study NR's effects on fatty acid metabolism in CRC cells. NR's targets and action mechanism in CRC were explored utilizing network pharmacology analysis and molecular docking. Changes in proteins involved in proliferation, apoptosis, epithelial-mesenchymal transition, fatty acid metabolism, and targets were determined via western blot. In vitro, NR suppressed CRC cell proliferation, migration, invasion, and fatty acid metabolism but promoted apoptosis. Invivo, NR inhibited tumor growth and reduced the levels of proteins related to proliferation and fatty acid metabolism. Moreover, NR directly targeted adenosine A3 receptor (ADORA3) and inhibited its expression. ADORA3 overexpression attenuated NR's inhibition of cell proliferation, invasion, and fatty acid metabolism. NR suppressed fatty acid metabolism and malignant biological behaviors of CRC cells, which was involved in the inhibition of ADORA3. This study reveals the anticancer activity of NR in CRC, providing experimental evidence for its further development as an adjuvant therapy or chemopreventive agent for CRC.

We investigated molecular characteristics and tissue distribution of elongation of very long chain fatty acids (ELOVL) genes in the chicken (Gallus gallus) genome. The research specifically examines the expression levels of these genes in chickens fed diets enriched with varying concentrations of curcumin. The aim is to uncover the potential roles and functions of ELOVL genes in the metabolism of fatty acids (FAs) in this species. In the experimental design, Hy-Line Brown commercial laying hens were selected for a feeding trial lasting 10 weeks. During this period, the hens were fed diets supplemented with curcumin at 100, 200, 300, and 400 mg/kg. The results revealed several critical insights: (1) It was confirmed that the ELOVL genes in Gallus gallus are orthologues of those found in vertebrates, indicating a shared evolutionary lineage; (2) There were noteworthy differences in how ELOVL genes, except ELOVL1 and ELOVL7, were distributed across various tissues and how they responded to dietary curcumin, prompting the need for comprehensive promoter analyses to better understand their functions in chickens; (3) The addition of curcumin to the diet did not increase omega-3 FAs in egg yolk; and (4) Dietary curcumin modulated ELOVL mRNA transcription in Gallus gallus. However, the intricate and multifaceted nature of FA metabolism presents challenges to fully grasping the implications of these results, highlighting the necessity for further in-depth investigations in this area.

Neuronal alpha-synuclein-mediated autophagy drives lipid droplets accumulation in astrocytes and microglia and aggravates ischemic stroke.

Comprehensive analysis of metabolic response in Arabidopsis thaliana under heavy metal stress by mass spectrometry.

Integration of transcriptomic and metabolomic data reveals the low temperature response gene regulatory network of germination in soybean (Glycine max L.).

Quantitative proteomic analysis of cadmium chloride tolerance mechanisms in Aeromonas hydrophila.

Baicalin attenuates pulmonary hypertension by targeting AMPK/CPT1A-mediated fatty acid metabolism.

Metabolism of p-chloro-m-xylenol by a newly isolated marine bacterium Rhodococcus ruber SJ-1: Cellular responses and detoxification mechanisms.

Identification of biomarkers for feed efficiency and growth rate by exploring the plasma metabolome of divergent heavy pigs.

Mitochondrial bioenergetics and intracellular calcium concentration in primary myotubes from mouse models of malignant hyperthermia.

CPT1A exacerbates trastuzumab-induced cardiotoxicity via promotion of mitochondrial dysfunction.

Lipid metabolism in cancer is regulated by the integrated natural product-miRNA-target axis.

The MBF complex orchestrates BbOSD-mediated lipid metabolism, development, oxidative stress, and pathogenic virulence in Beauveria bassiana.

Interscapular white adipose tissue: An interesting depot for browning research in rodents.

Integrated base editing and microfluidics boost microbial lipid production from lignin.

Cold exposure triggers distinct RNA editing, alternative splicing, and gene expression patterns in cold domestication pufferfish (Takifugu obscurus).

Breathomics profiling facilitates personalized screening for colorectal cancer.

Background: Atherosclerosis remains a major global health burden. Sialic acid (N-acetylneuraminic acid, Neu5Ac) and its derivative 3'-sialyllactose (3'-SL) show potential for prevention, but their mechanisms of action are unclear. This study investigated their prophylactic effects and underlying mechanisms in an atherosclerotic model. Methods: Forty male LDLR-/- mice were randomly assigned to four groups (n = 10 per group): (1) high-cholesterol diet (HCD) control, (2) HCD + Neu5Ac (oral), (3) HCD + 3'-SL (oral) and (4) normal chow control. Ten wild-type C57BL/6J mice served as baseline controls. After 12 weeks of intervention, atherosclerotic plaque formation, serum lipids (total cholesterol (TC), triglycerides (TG), LDL and HDL), inflammatory markers (hs-CRP, IL-1β and TNF-α), hepatic lipid deposition, coronary chemokines (CXCL1 and CCL5), LOX-1, and cytokines (IL-18 and IFN-γ) were assessed. Multi-omics analyses (16S rRNA sequencing for the gut microbiota, hepatic transcriptomics, and metabolomics) were performed. Statistical analysis used one-way or two-way ANOVA followed by Tukey's post-hoc test, with P < 0.05 considered significant. Results: Both Neu5Ac and 3'-SL significantly attenuated atherosclerosis compared to HCD controls. Key findings included: reduced serum inflammation (hs-CRP, IL-1β and TNF-α) and improved lipid profiles (reduced TC, TG, LDL and increase HDL); decreased hepatic lipid deposition; lowered coronary chemokines (CXCL1 and CCL5), LOX-1, and pro-inflammatory cytokines (IL-18 and IFN-γ); and diminished atherosclerotic plaque formation. Multi-omics revealed synergistic protection involving: metabolic remodeling (coordinated regulation of cholesterol, fatty acid, and bile acid metabolism); anti-inflammatory/antioxidant effects (suppression of pro-inflammatory pathways and oxidative stress); and multi-organ protection (enhanced gut barrier integrity/pathogen clearance; upregulated hepatic detoxification/reduced steatosis; stabilized coronary extracellular matrix/endothelial function). It is noteworthy that 3'-SL primarily modulates the gut microbiota and its metabolites, thereby indirectly ameliorating liver and coronary lesions, whereas Neu5Ac could be absorbed directly to improve liver metabolism and exert anti-inflammatory effects. Conclusions: Neu5Ac and 3'-SL exert potent prophylactic effects against HCD-induced atherosclerosis in LDLR-/- mice. These effects are mediated through synergistic modulation of metabolic, inflammatory, and microbial pathways along the gut-liver-coronary axis. This axis integrates lipid metabolism, inflammation, and oxidative stress responses, highlighting a novel multi-targeted mechanism for atheroprotection. These findings support the potential of sialylated compounds as dietary interventions for atherosclerosis prevention.