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  • ||||||||||  Journal:  Characterization of the circRNA Landscape in Interleukin-4 Induced Anti-Inflammatory Microglia. (Pubmed Central) -  Dec 23, 2023   
    We found that circAdgre1 promoted IL-4-induced anti-inflammatory responses and further conferred neuroprotective effects upon lipopolysaccharide (LPS) stimuli. Taken together, our results show that circRNAs might be possible therapeutic targets for microglia-mediated neuroinflammation and neurodegenerative diseases.
  • ||||||||||  Voluntary wheel running in old mice reduces age-related inflammation in the colon (WCC Halls A-C) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_8259;    
    The main finding of our study is that both the hippocampus and colon exhibit an increase in inflammatory markers during aging, and that voluntary wheel running in old age exclusively attenuates intestinal inflammation. Based on the existence of the gut-brain axis, our results extend therapeutic approaches preserving cognitive functions in the elderly to the colon.
  • ||||||||||  Immune Modulation to Treat Ischemic Heart Failure (Moderated Digital Posters 5, Science and Technology Hall, Level 2) -  Aug 12, 2023 - Abstract #AHA2023AHA_2589;    
    IF demonstrated a novel immune response in the treated group absent in the controls. This response is isolated to the epicardial infarct-patch interface.
  • ||||||||||  Journal:  mthl1, a potential Drosophila homologue of mammalian adhesion GPCRs, is involved in antitumor reactions to injected oncogenic cells in flies. (Pubmed Central) -  Jul 21, 2023   
    Of great potential interest is our observation that the expression of the mouse gene coding for the adhesion G-protein-coupled receptor E1 (Adgre1, also known as F4/80), a potential mammalian homologue of mthl1, is significantly induced by B16-F10 melanoma cell inoculation 3 d postinjection in both the bone marrow and spleen (nests of immature and mature myeloid-derived immune cells), respectively. This observation is compatible with a role of this GPCR in the early response to injected tumor cells in mice.
  • ||||||||||  Preclinical, Journal:  Post-Effects of Time-Restricted Feeding against Adipose Tissue Inflammation and Insulin Resistance in Obese Mice. (Pubmed Central) -  Jun 14, 2023   
    The post-TRF animals displayed liver mass similar to those in the TRF group, but the TRF effects on the mRNA of inflammation markers in the liver vanished completely. Together, these results indicate that, although the lasting effects of TRF may differ by tissues and genes, the impact of TRF on adipose tissue inflammation and immune cell infiltration could last a couple of weeks, which may, in part, contribute to the maintenance of insulin sensitivity even after the cessation of TRF.
  • ||||||||||  Preclinical, Journal:  Central growth hormone action regulates neuroglial and proinflammatory markers in the hypothalamus of male mice. (Pubmed Central) -  Apr 28, 2023   
    Conversely, brain-specific GHR knockout mice showed reduced expression of Gfap, Adgre1, and Vim (vimentin), indicating that brain GHR signaling is necessary to mediate GH-induced changes in the expression of several neuroglial markers. In conclusion, the hypothalamic mRNA levels of several neuroglial markers associated with inflammation are directly modulated by GHR signaling in male mice.
  • ||||||||||  SGLT2 Inhibitors Exert Anti-inflammatory and Antioxidant Effects in Epicardial Adipose Tissue of Severe Heart Failure Subjects (Room 28; [Board No. 37]) -  Apr 10, 2023 - Abstract #ADA2023ADA_149;    
    Finally, enhanced enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests reduced disposition to ferroptosis (iron-dependent lipid peroxidation-regulated cell death) further contributing to decreased oxidative stress in EAT of SGLT-2i subjects. In conclusion, SGLT-2i treatment is associated with reduced inflammation and oxidative stress in EAT, which could at least partially explain their cardioprotective effects.
  • ||||||||||  Journal:  FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation. (Pubmed Central) -  Mar 13, 2023   
    Our data demonstrate a distinct set of FOXP3+ macrophages with enhanced scavenging capability, which could be a target in immunomodulatory therapy against AIS.Abbreviations: ADGRE1/F4/80: adhesion G protein-coupled receptor E1; AIF1/Iba1: allograft inflammatory factor 1; AIS: acute ischemic stroke; ARG1: arginase 1; ATP: adenosine triphosphate; BECN1/Beclin1: Beclin 1, autophagy related; BMDM: bone marrow-derived macrophages; CKO: conditional knockout; CSF1/M-CSF: colony stimulating factor 1 (macrophage); CSF2/GM-CSF: colony stimulating factor 2; CSF3/G-CSF: colony stimulating factor 3; CUT & RUN: cleavage under targets and release using nuclease; CyD: cytochalasin D; DAMP: danger/damage-associated molecular pattern; DIL: dioctadecyl-3,3,3,3-tetramethylin docarbocyanine; ELISA: enzyme linked immunosorbent assay; GO: Gene Ontology; FCGR3/CD16: Fc receptor, IgG, low affinity III; HMGB1: high mobility group box 1; IFNG/IFN?: interferon gamma; IP: immunoprecipitation; KEGG: Kyoto Encyclopedia of Genes and Genomes; ITGAM/CD11b: integrin subunit alpha M; ITGAX/CD11c: integrin subunit alpha X; LAP: LC3-associated phagocytosis; LC-MS: liquid chromatography-mass spectrometry; LPS: lipopolysaccharide; MRC1/CD206: mannose receptor, C type 1; O4: oligodendrocyte marker O4; PBMC: peripheral blood mononuclear cells; RBC: red blood cells; PTPRC/CD45: protein tyrosine phosphatase, receptor type, C; RBFOX3/NeuN: RNA binding protein, fox 1 homolog (C. elegans) 3; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; scRNAseq: single cell RNA sequencing; SQSTM1/p62 (sequestosome 1); TGFB/TGF?: transforming growth factor, beta; tMCAO: transient middle cerebral artery occlusion; TNF/TNF?: tumor necrosis factor; Treg: regulatory T cell.
  • ||||||||||  epacadostat (INCB024360) / Incyte, Turalio (pexidartinib) / Daiichi Sankyo
    CAR-T Cell Therapy of Solid Tumors Invokes an Expanded Set of Myeloid Cells in an Orthotopic Tumor Model for Rhabdomyosarcoma (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_6446;    
    The origin of myeloid cells within an i.m. tumor lesion can arise from mis-differentiated bone marrow-derived cells that infiltrate the lesion, from monocytes responding to tissue-generated signals, from tissue resident macrophages already present, or from innate myeloid cells present in muscle tissue that were generated embryonically from liver or even earlier from the AGM (aorta gonad mesonephros), and which have their own intrinsic tissue regulatory biology. The strongest transcript expressed was for an uncharacterized protein, GM52800, indicating there is much to discover in the biology of tumor-associated myeloid cells, especially in the context of CAR-T therapy.
  • ||||||||||  Preclinical, Journal, BRCA Biomarker:  miR155 deficiency reduces breast tumor burden in the MMTV-PyMT mouse model. (Pubmed Central) -  Oct 27, 2022   
    Overall, miR155 deficiency reduced BrCA and improved the tumor microenvironment through the reduction of genes associated with pro-tumorigenic processes. However, given the inconsistencies in the literature, additional studies are needed before any attempts are made to harness miR155 as a potential oncogenic or tumor suppressive miRNA.
  • ||||||||||  PF-8380 / Pfizer
    Journal:  A defective lysophosphatidic acid-autophagy axis increases miscarriage risk by restricting decidual macrophage residence. (Pubmed Central) -  Oct 4, 2022   
    In therapeutic studies, supplementation with LPA or the autophagy inducer rapamycin significantly promotes dMφ autophagy and cell residence, and improves embryo resorption in Enpp2 and spontaneous abortion mouse models, which should be dependent on the activation of DDIT4-autophagy-CLDN7-adhesion molecules axis. This observation reveals that inactivation of ENPP2-LPA metabolism and insufficient autophagy of dMφ result in resident obstacle of dMφ and further increase the risk of spontaneous abortion, and provides potential therapeutic strategies to prevent spontaneous abortion.Abbreviations: ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; Atg5: autophagy related 5; ATG13: autophagy related 13; BECN1: beclin 1; CDH1/E-cadherin: cadherin 1; CDH5/VE-cadherin: cadherin 5; CFSE: carboxyfluorescein succinimidyl ester; CLDN7: claudin 7; CSF1/M-CSF: colony stimulating factor 1; CSF2/GM-CSF: colony stimulating factor 2; Ctrl: control; CXCL10/IP-10: chemokine (C-X-C) ligand 10; DDIT4: DNA damage inducible transcript 4; dMφ: decidual macrophage; DSC: decidual stromal cells; ENPP2/ATX: ectonucleotide pyrophosphatase/phosphodiesterase 2; Enpp2: Enpp2 heterozygous knockout mouse; ENPP2i/PF-8380: ENPP2 inhibitor; EPCAM: epithelial cell adhesion molecule; ESC: endometrial stromal cells; FGF2/b-FGF: fibroblast growth factor 2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GPCPD1: glycerophosphocholine phosphodiesterase 1; HE: heterozygote; HIF1A: hypoxia inducible factor 1 subunit alpha; HNF4A: hepatocyte nuclear factor 4 alpha; HO: homozygote; ICAM2: intercellular adhesion molecule 2; IL: interleukin; ITGAV/CD51: integrin subunit alpha V; ITGAM/CD11b: integrin subunit alpha M; ITGAX/CD11b: integrin subunit alpha X; ITGB3/CD61: integrin subunit beta 3; KLRB1/NK1.1: killer cell lectin like receptor B1; KRT7/cytokeratin 7: keratin 7; LPA: lysophosphatidic acid; LPAR: lysophosphatidic acid receptor; lpar1: lpar1 homozygous knockout mouse; LPAR1i/AM966: LPAR1 inhibitor; LY6C: lymphocyte antigen 6 complex, locus C1; LYPLA1: lysophospholipase 1; LYPLA2: lysophospholipase 2; Lyz2: lysozyme 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MARVELD2: MARVEL domain containing 2; 3-MA: 3-methyladenine; MBOAT2: membrane bound O-acyltransferase domain containing 2; MGLL: monoglyceride lipase; MRC1/CD206: mannose receptor C-type 1; MTOR: mechanistic target of rapamycin kinase; NP: normal pregnancy; PDGF: platelet derived growth factor; PLA1A: phospholipase A1 member A; PLA2G4A: phospholipase A2 group IVA; PLPP1: phospholipid phosphatase 1; pMo: peripheral blood monocytes; p-MTOR: phosphorylated MTOR; PPAR: peroxisome proliferator activated receptor; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; PPARGi/GW9662: PPARG inhibitor; PTPRC/CD45: protein tyrosine phosphatase receptor type, C; Rapa: rapamycin; RHEB: Ras homolog, mTORC1 binding; SA: spontaneous abortion; SELE: selectin E; SELL: selectin L; siCLDN7: CLDN7-silenced; STAT: signal transducer and activator of transcription; SQSTM1: sequestosome 1; TJP1: tight junction protein 1; VCAM1: vascular cell adhesion molecule 1; WT: wild type.
  • ||||||||||  Pain in Osteoarthritis - Identification of GPR34 and GPR150 as Novel Targets in the Dorsal Root Ganglia (Room 108) -  Sep 17, 2022 - Abstract #ACRConvergence2022ACR_CONVERGENCE_3663;    
    We have shown that the number of DRG macrophages is increased in an experimental model of OA (PMX), and that Gpr34 is specifically expressed by DRG macrophages. Since these are druggable targets, our findings open new avenues for exploring the effect of targeting either non-neuronal cells (macrophages expressing GPR34) or neuronal cells (GRP150) in models of OA pain.
  • ||||||||||  Q&A (Moderated Digital Posters 1) -  Aug 11, 2022 - Abstract #AHA2022AHA_3745;    
    Since these are druggable targets, our findings open new avenues for exploring the effect of targeting either non-neuronal cells (macrophages expressing GPR34) or neuronal cells (GRP150) in models of OA pain. There is no abstract associated with this presentation.
  • ||||||||||  probenecid / Generic mfg.
    Journal:  Microcystin-LR incorporated into colonic cells through probenecid-sensitive transporters leads to upregulated MCP-1 expression induced by JNK activation. (Pubmed Central) -  Jul 27, 2022   
    The findings of transporter inhibitors indicated that microcystin-LR is incorporated into cells via ATP Binding Cassette (ABC) or solute carrier (SLC) transporters other than the organic anion transporting polypeptides (OATPs)1B1, 1B3, 2B1, and 1A2, which this leads to increased MCP-1 expression in the colon through activating JNK. Thus, increased MCP-1 expression induced by microcystin-LR might be a trigger for initiating tumorigenesis with inflammation in the colon because increased MCP-1 expression induces inflammation associated with macrophage infiltration into the colon, and chronic inflammation is associated with the initiation of tumorigenesis.
  • ||||||||||  Journal, IO biomarker:  A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets in Uterine Corpus Endometrial cancer. (Pubmed Central) -  Jun 22, 2022   
    Thus, increased MCP-1 expression induced by microcystin-LR might be a trigger for initiating tumorigenesis with inflammation in the colon because increased MCP-1 expression induces inflammation associated with macrophage infiltration into the colon, and chronic inflammation is associated with the initiation of tumorigenesis. The adhesion GPCRs, especially ADGRF1, might be used as immunotherapeutic targets and prognostic markers of UCEC.
  • ||||||||||  5-fluorouracil / Generic mfg.
    5-Fluorouracil Alters Skeletal Muscle Mitochondrial Content And Inflammation In Mice (Exhibit Hall F) -  Jun 2, 2022 - Abstract #ACSM2022ACSM_1485;    
    Collectively, these results demonstrate 1 cycle of 5FU notably impacts mitochondrial content and inflammation concomitant with decreases in body weight and cage activity. While changes in skeletal muscle function were not found, the observed changes in mitochondria and the inflammatory micro-environment may precede the functional decrements in skeletal muscle.
  • ||||||||||  Journal:  Altered Adipose Tissue Inflammatory Markers in Mothers With Gestational Diabetes. (Pubmed Central) -  May 14, 2022   
    Our study established a novel signature consisting of 7 hub genes for the prognostic prediction in patients with HNSCC. Data support that mothers with GDM differentially express AT adipokines and genes associated with inflammation, insulin resistance and altered lipid metabolism than mothers with NGT.
  • ||||||||||  DEPLETION OF HEPATIC STELLATE CELLS REDUCES HEPATIC STEATOSIS (ePoster - DDW Virtual) -  Apr 25, 2022 - Abstract #DDW2022DDW_1502;    
    Compared with that of hepatocyte monoculture, intracellular TG level was significantly higher in the presence of HSCs. Conclusion s: As observed in the in vitro experiment, HSCs enhanced steatosis of hepatocytes, and depletion of HSCs in mice treated with GTX prevented hepatic steatosis and fibrogenesis, suggesting that HSCs are promising targets in the treatment of NASH.
  • ||||||||||  MODELING MACROPHAGE-ENTERIC NEURON INTERCELLULAR COMMUNICATION AT SINGLE CELL LEVEL (Poster Hall - San Diego Convention Center) -  Apr 25, 2022 - Abstract #DDW2022DDW_1232;    
    Conclusion s: Nichenet represents a new tool for decoding MMs-ENs communication at single-cell level in an unbiased fashion. Multiple interactions were identified, and further studies are needed to functionally dissect the interactions described by this model.Supported by DK127992, ANMS Young Investigator grant and AGA grant#36, P30DK084567, DK115255.
  • ||||||||||  Preclinical, Journal:  Voluntary Wheel Running in Old C57BL/6 Mice Reduces Age-Related Inflammation in the Colon but Not in the Brain. (Pubmed Central) -  Apr 9, 2022   
    The main finding of our study is that both the hippocampus and colon exhibit an increase in inflammatory markers during aging, and that voluntary wheel running in old age exclusively attenuates intestinal inflammation. Based on the existence of the gut-brain axis, our results extend therapeutic approaches preserving cognitive functions in the elderly to the colon.
  • ||||||||||  Journal:  Keratinocyte autophagy enables the activation of keratinocytes and fibroblasts and facilitates wound healing. (Pubmed Central) -  Apr 8, 2022   
    At the cellular level, we found that CCL2 induction via autophagy in keratinocytes is required not only for keratinocyte migration and proliferation but also for dermal fibroblast activation. Our findings demonstrate a critical role of epidermal autophagy in wound healing in vivo and elucidate a critical molecular machinery coordinating keratinocyte-fibroblast interaction in skin repair.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. (Pubmed Central) -  Apr 8, 2022   
    Targeting TXNIP may be a potential therapeutic approach for NASH. Abbreviations: ACOX1: acyl-Coenzyme A oxidase 1, palmitoyl; ACSL1: acyl-CoA synthetase long-chain family member 1; ACTA2/α-SMA: actin, alpha 2, smooth muscle, aorta; ACTB: actin beta; ADGRE1/F4/80: adhesion G protein-coupled receptor E1; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BafA1: bafilomycin A1; COL1A1/Col1α1: collagen, type I, alpha 1; CPT1A: carnitine palmitoyltransferase 1a, liver; CQ: chloroquine; DGAT1: diacylglycerol O-acyltransferase 1; DGAT2: diacylglycerol O-acyltransferase 2; ECI2/Peci: enoyl-Coenzyme A isomerase 2; EHHADH: enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase; FAO: fatty acid oxidation; FASN: fatty acid synthase; FFA: free fatty acids; GFP: green fluorescent protein; GK/GYK: glycerol kinase; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPAM: glycerol-3-phosphate acyltransferase, mitochondrial; GPT/ALT: glutamic pyruvic transaminase, soluble; H&E: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; IOD: integral optical density; KO: knockout; Leu: leupeptin; LPIN1: lipin 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MCD: methionine choline-deficient; MMP9: matrix metallopeptidase 9; mRNA: messenger RNA; MTORC1: mechanistic target of rapamycin kinase complex 1; NAFLD: nonalcoholic fatty liver diseases; NASH: nonalcoholic steatohepatitis; PA: palmitic acid; PPARA/PPARα: peroxisome proliferator activated receptor alpha; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; qRT-PCR: quantitative real-time PCR; RPS6KB1/p70S6K1: ribosomal protein S6 kinase, polypeptide 1; RPTOR: regulatory associated protein of MTOR complex 1; SCD1: stearoyl-Coenzyme A desaturase 1; SEM: standard error of the mean; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TG: triglyceride; TGFB/TGF-β: transforming growth factor, beta; TIMP1: tissue inhibitor of metalloproteinase 1; TNF/TNF-α: tumor necrosis factor; TXNIP/VDUP1: thioredoxin interacting protein; WT: wild-type.
  • ||||||||||  Elucidating the impact of obesity and weight loss on breast cancer tumor progression (Section 14) -  Mar 9, 2022 - Abstract #AACR2022AACR_5091;    
    Future studies will focus on understanding the mechanistic links between heightened inflammation in obese and WL adipose tissue and tumor progression. Additionally, we aim to elucidate the contribution of Trem2-expressing immune cells to tumor progression in the obese and WL contexts.
  • ||||||||||  Journal:  Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux. (Pubmed Central) -  Jan 14, 2022   
    Noteworthy, the efficacy of EPA on lipotoxicity is autophagy-dependent and cell-intrinsic. In conclusion, EPA counteracts lipotoxicity in the proximal tubule by alleviating autophagic numbness, making it potentially suitable as a novel treatment for obesity-related kidney diseases.
  • ||||||||||  Review, Journal:  Immune responses to injury and their links to eye disease: Immune responses to wounding in the eye. (Pubmed Central) -  Oct 1, 2021   
    Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.
  • ||||||||||  Journal:  Luteolin inhibits NLRP3 inflammasome activation via blocking ASC oligomerization. (Pubmed Central) -  Aug 25, 2021   
    Luteolin inhibited the activation step of NLRP3 inflammasome by interfering with ASC oligomerization. Taken together, these findings suggest that luteolin supplementation may suppress NLRP3 induction and activation process and thus potentially would be protective against NLRP3-mediated inflammatory diseases.