Essentiality of SLC7A11-mediated nonessential amino acids in MASLD

Science Bulletin, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Isobutyrate confers resistance to inflammatory bowel disease through host-microbiota interactions in pigs

Research, Год журнала: 2025, Номер 8

Опубликована: Янв. 1, 2025

Supplementation with short-chain fatty acids (SCFAs) is a potential therapeutic approach for inflammatory bowel disease (IBD). However, the effects and mechanisms of action isobutyrate in IBD remain unclear. Clinical data indicate that fecal levels are markedly lower patients Crohn’s than healthy controls. Compared mice pigs, pigs colitis presented significantly levels. Furthermore, level was negatively correlated activity index. We speculate may play crucial role regulating host gut homeostasis. established model dextran sulfate sodium-induced which have gastrointestinal structure function similar to those humans; we performed multiomic analysis investigate on at both animal cellular validated results. Phenotypically, can alleviate diarrhea, bloody stools, weight loss, colon shortening caused by pigs. Mechanistically, increase relative abundance Lactobacillus reuteri , thereby increasing production indole-3-lactic acid, aryl hydrocarbon receptor expression downstream signaling pathways, Foxp3 + CD4 T cell recruitment colitis. Isobutyrate directly activate G protein-coupled 109A, promote Claudin-1, improve intestinal barrier function. In addition, SCFAs 3-hydroxybutyric acid inhibit TLR4/MyD88/NF-κB pathway suppress inflammation. conclusion, our findings demonstrate confers resistance through host–microbiota interactions, providing theoretical basis use alleviating

Язык: Английский

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Metabolic reprogramming shapes post-translational modification in macrophages

Molecular Aspects of Medicine, Год журнала: 2025, Номер 102, С. 101338 - 101338

Опубликована: Фев. 19, 2025

Язык: Английский

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Guiding Microbial Distribution by Regulating Oxygen Supply for the Fabrication of Integrated Artificial Auricles

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

Abstract Auricular reconstruction is a key method for treating auricular deformities; however, the primary challenge creation of an integrated scaffold that accurately replicates complex 3D structure auricle. In this study, oxygen‐demanding properties Komagataeibacter xylinus are leveraged to guide microbial distribution in three dimensions by regulating oxygen supply within bioreactor, which enabled production artificial with detailed profile. These results indicate manufacturing approach can be used effectively design and fabricate scaffolds varying sizes intricate structures. The exhibited excellent mechanical properties, remained stable non‐degradable over 50 days, showed good biocompatibility human chondrocytes dermal fibroblasts. Subcutaneous implantation Sprague‐Dawley rats successfully into surrounding tissues without causing rejection. This using microorganisms holds significant promise offers viable alternative clinical reconstruction.

Язык: Английский

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Glucuronolactone Restores the Intestinal Barrier and Redox Balance Partly Through the Nrf2/Akt/FOXO1 Pathway to Alleviate Weaning Stress-Induced Intestinal Dysfunction in Piglets

Antioxidants, Год журнала: 2025, Номер 14(3), С. 352 - 352

Опубликована: Март 18, 2025

(1) Background: Glucuronolactone (GLU) is a glucose metabolite with antioxidant activity. At present, the exact role of it in regulating intestinal health piglets under weaning stress not clear. The purpose this study to investigate effects GLU on growth performance and explore potential mechanisms. (2) Methods: Twenty-four weaned were randomly assigned into two groups, one group receiving basal diet other an experimental supplemented 200 mg/kg GLU. (3) Results: increased ADG, ADFI, final body weight piglets, while reducing diarrhea rate. Mechanistically, alleviates stress-induced oxidative inflammatory responses partly through activating Nrf2-Akt signaling pathway suppress transcriptional activity FOXO1, also inhibiting activation TLR4-MAPK reduce secretion pro-inflammatory cytokines. Moreover, relative abundance Lactobacillus reuteri ileum improved composition gut microbiota. (4) Conclusions: reduced inflammation Nrf2/Akt/FOXO1 health, resulting piglets.

Язык: Английский

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Ectopic expression of Slc1a2 in the prefrontal cortex of sleep-deprived male mice counteracts the glutamate/GABA-glutamine dysfunction

BMC Biology, Год журнала: 2025, Номер 23(1)

Опубликована: Март 26, 2025

Язык: Английский

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Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 28, 2025

Background. The ε4 isoform of apolipoprotein E (ApoE) is the most significant genetic risk factor for Alzheimer’s disease. Glial cells are main source ApoE in brain, and microglia, has been shown to impair mitochondrial metabolism uptake lipids Aβ42. However, whether alters autophagy or lysosomal activity microglia basal inflammatory conditions unknown. Methods. Altogether, microglia-like (iMGs) from eight APOE3/3 six APOE4/4 human induced pluripotent stem cell (iPSC) lines were used this study. responses iMGs Aβ42, LPS IFNγ studied by metabolomics, proteomics, functional assays. Results. Here, we demonstrate that with genotype exhibit reduced level pinocytosis an overall downregulation proteins compared iMGs. Inflammatory stimulation a combination Aβ42 PI3K/AKT/mTORC signaling pathway, increased pinocytosis, blocked autophagic flux, leading accumulation sequestosome 1 both Exposure furthermore caused membrane permeabilization, which was significantly stronger positively correlated secretion proinflammatory chemokine IL-8. Metabolomics analysis indicated dysregulation amino acid metabolism, primarily L-glutamine, Conclusions. Overall, our results suggest inflammation-induced metabolic reprogramming places lysosomes under substantial stress. Lysosomal stress more detrimental defects biogenesis.

Язык: Английский

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Streptococcus suis regulates central carbon fluxes in response to environment to balance drug resistance and virulence

Microbiological Research, Год журнала: 2025, Номер unknown, С. 128157 - 128157

Опубликована: Март 1, 2025

Язык: Английский

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The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease

Biomolecules, Год журнала: 2025, Номер 15(4), С. 525 - 525

Опубликована: Апрель 3, 2025

The vacuolar-type ATPase (V-ATPase) is a multi-subunit enzyme complex that maintains lysosomal acidification, critical process for cellular homeostasis. By controlling the pH within lysosomes, V-ATPase contributes to overall homeostasis, helping maintain balance between degradation and synthesis of components. Dysfunction impairs leading accumulation undigested materials contributing various diseases, including cardiovascular diseases (CVDs) like atherosclerosis myocardial disease. Furthermore, V-ATPase's role in function suggests potential therapeutic strategies targeting this mitigate disease progression. Understanding mechanisms by which influences pathology essential developing novel treatments aimed at improving outcomes patients with heart vascular diseases.

Язык: Английский

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Asparagine transporter supports macrophage inflammation via histone phosphorylation

Science Advances, Год журнала: 2025, Номер 11(15)

Опубликована: Апрель 9, 2025

Solute carrier (SLC) family is essential for immune responses; nevertheless, whether and how SLCs regulate macrophage inflammation remains unclear. Here, we demonstrate that K636 acetylation mediates high abundance of SLC6A14 in inflammatory macrophages. Notably, the pharmacological inhibition or genetic modulation reduces interleukin-1β (IL-1β) secretion dependently lower asparagine uptake subsequently enhanced nuclear LKB1. Mechanistically, LKB1 lessens MAPK pathway–mediated NLRP3 inflammasome activation by increased histone 3 S10/28 phosphorylation-dependent cyclin O transcription. Moreover, myeloid Slc6a14 deficiency alleviates pulmonary via suppressing responses. Overall, these results uncover a network which SLC6A14-mediated orchestrates through phosphorylation, providing crucial target diseases.

Язык: Английский

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