Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 29, 2024
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Сен. 20, 2024
Язык: Английский
Процитировано
33
Cell Death and Disease, Год журнала: 2024, Номер 15(1)
Опубликована: Янв. 13, 2024
Abstract Acute lung injury (ALI) as well its more severe form, acute respiratory distress syndrome (ARDS), frequently leads to an uncontrolled inflammatory response. N 6 -methyladenosine (m A) modification was associated with the progression of several diseases. However, role methyltransferase-like 14 (METTL14)-mediated m A methylation in ALI/ARDS remains unclear. Here, we reported increase overall expression levels and METTL14 circulating monocyte-derived macrophages recruited following ALI, which is correlated severity injury. We further demonstrated critical function activating NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome vitro mouse models ALI/ARDS, validated NLRP3 downstream target by RNA immunoprecipitation (MeRIP) RIP assays. Mechanistically, METTL14-methylated transcripts were subsequently recognized insulin-like growth factor 2 mRNA-binding (IGF2BP2), reader, stabilized mRNA. Furthermore, observed that IGF2BP2 knockdown diminished LPS-induced ALI mice downregulating expression. In summation, our study revealed molecular mechanism underlying pathogenesis involves METTL14-mediated activation dependent manner, thereby demonstrating potential promising biomarkers therapeutic targets for treatment.
Язык: Английский
Процитировано
13
Inflammation Research, Год журнала: 2024, Номер 73(4), С. 641 - 654
Опубликована: Фев. 27, 2024
Язык: Английский
Процитировано
9
Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 165, С. 105848 - 105848
Опубликована: Авг. 13, 2024
Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated relationship between T2D-related and activation polarization of microglia. This review summarizes potential mechanisms microglial context T2D. It discusses inflammatory responses, neuronal apoptosis, amyloid-β deposition, abnormal phosphorylation Tau protein mediated by polarization, exploring connections from multiple perspectives. Additionally, this provides references for future treatment targeting microglia clinical translation.
Язык: Английский
Процитировано
9
Ageing Research Reviews, Год журнала: 2025, Номер 105, С. 102691 - 102691
Опубликована: Фев. 13, 2025
Язык: Английский
Процитировано
1
Molecular Neurobiology, Год журнала: 2024, Номер 61(10), С. 7796 - 7813
Опубликована: Март 2, 2024
Язык: Английский
Процитировано
7
Journal of Clinical Investigation, Год журнала: 2024, Номер 134(12)
Опубликована: Июнь 16, 2024
STING agonists can reprogram the tumor microenvironment to induce immunological clearance within central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and Ivy Glioblastoma Atlas, expression was found in myeloid populations perivascular space. The agonist 8803 increased median survival multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% mice were cured. Ex vivo flow cytometry profiling during therapeutic window demonstrated increases trafficking activation, alongside enhancement CD8+ T cell NK effector responses. Treatment with reprogrammed microglia express costimulatory CD80/CD86 iNOS, while decreasing immunosuppressive CD206 arginase. In humanized mice, is epigenetically silenced, activity maintained, further attesting dependency reprogramming. Although combination a STAT3 inhibitor did not enhance activity, addition anti-PD-1 antibodies treatment enhanced blockade-responsive glioma model. summary, as monotherapy demonstrates marked meriting consideration for clinical translation.
Язык: Английский
Процитировано
7
Molecular Neurobiology, Год журнала: 2024, Номер 61(9), С. 6997 - 7008
Опубликована: Фев. 16, 2024
Язык: Английский
Процитировано
6
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Фев. 6, 2025
ABSTRACT Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation drinking. Given the challenge longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from non-human primates (NHP) into microglia-like (induced-microglia; iMGL). The iMGLs displayed transcriptional profiles distinct those monocyte progenitors closely resembling microglia. Notably, morphological features showed that differentiated derived NHPs chronic consumption (CAC) possessed a more mature-like morphology. Additionally, key inflammatory regulatory markers alongside increased baseline phagocytic was observed CAC-derived IMGLs resting state. Phenotypic functional assessments following LPS stimulation indicated presence immune-tolerant phenotype enrichment CD86 + hyper-inflammatory subpopulation ethanol-exposed animals. Collectively, these findings demonstrate differentiation PBMC offers minimally invasive approach studying impact CAC on function revealing reshapes both
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189299 - 189299
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0