Induced expression of serum amyloid A (SAA) is a hallmark many inflammatory diseases, but whether SAA exacerbates inflammation or protects tissues against injury remains unclear. In dextran sulfate sodium (DSS)-induced colitis, SAA3 the predominant isoform inducible proteins that also include SAA1 and SAA2, mice with genetic deletion Saa3 exhibits increased production proinflammatory cytokines, decreased IL-22 along aggravated epithelium disruption, reduced colon length compared wild-type...

The identification of exogenous ligands from natural products is an alternative strategy to explore the unrevealed physiological functions orphan G-protein-coupled receptors (GPCRs). In this study, we have successfully identified and pharmacologically characterized licoisoflavone A (LIA) as a novel selective antagonist BRS-3, GPCR. Functional studies showed that pretreatment with LIA ameliorated hydrogen peroxide (H2O2)-induced cardiomyocyte injury. Furthermore, significantly restored...

Kidney fibrosis is a key pathological feature in the progression of chronic kidney disease (CKD), traditionally diagnosed through invasive biopsy. This study aimed to develop and validate noninvasive, multi-center predictive model incorporating machine learning (ML) for assessing severity using biochemical markers. retrospective included 598 patients with from four hospitals. A training cohort 360 Shanghai Tongji Hospital was used nomogram ML model, classified as mild or moderate-to-severe...

Fifteen unreported compounds in Anemarrhena asphodeloides, iriflophene (3), hostaplantagineoside C (7), tuberoside G (8), spicatoside B (9), platycodin D (14), platycoside A (15), D2 (16), polygalacin (17), D3 (18), isovitexin (20), vitexin (21), 3,4-dihydroxyallylbenzene-3-O-α-l-rhamnopyranosyl(1→6)-β-d-glucopyranoside (22), iryptophan (24), adenosine (25), α-d-Glucose monoallyl ether (26), together with eleven known (1, 2, 4–6, 10–13, 19 and 23), were isolated from the rhizomes of...

Telekin, a eudesmane-type sesquiterpene lactone compound isolated from Chinese folk medicine Carpesium divaricatum, has been reported to strongly inhibit the proliferation of cancer cells. In this study, involvement mitochondria-mediated pathway in pro-apoptotic action telekin was investigated human hepatocellular carcinoma 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that exhibited excellent anti-proliferation activity cells and low cytotoxicity normal...

4'-Hydroxywogonin (4'-HW), a flavonoid, has been isolated from various plants and shown to inhibit NO production in macrophages. However, the molecular mechanisms its vivo activity have not determined. Our study aimed investigate underlying anti-inflammatory effects of 4'-HW vitro vivo. We showed that potently reduced expression levels COX-2 iNOS as well their products, prostaglandin E2 (PGE2) nitric oxide (NO) respectively, LPS-stimulated RAW 264.7 also suppressed LPS-induced...

In a continuing effort to discover more anti-inflammatory medicinal plants in China, the activities of 101 extracts from different parts 84 traditional were evaluated by panel vitro and vivo assays. Nuclear factor-kappa B (NF- κ B) inhibitory effects determined luciferase assay stably transfected Hela cells. Cytotoxic assessed using MTT assay. Inhibitory on LPS-induced nitric oxide production proinflammatory mediators Griess reaction Real-Time PCR analysis, respectively. examined...

Corydalis yanhusuo W. T. Wang (C. yanhusuo) has been traditionally used for drug addiction and pain relief in China. In our previous study, we showed that the extract of C. blocks dopamine receptors, demonstrating its pharmacological activities are mostly due to antagonistic effects some components at receptors. As part ongoing project on yanhusuo, aim present study is establish a high-throughput low-cost screening assay system test abilities isolated alkaloids from inhibit dopamine-induced...

Bombesin receptor subtype-3 (BB3, BRS-3) is an orphan Gαq protein-coupled receptor. The characterization of novel synthetic ligands for BB3 alternative and attractive strategy to study its diverse physiological functions. Here, we uncovered the intimate pairing DMAKO-00 derivatives with BB3. Dimethyl shikonin oxime 5a (DSO-5a) was identified as most potent agonist (pEC50 = 8.422 in IP-1 accumulation), which 898-fold more than DMAKO-00. Importantly, without brain penetration, DSO-5a improved...

Bombesin-like receptor 3 (BRS3), an orphan G protein-coupled (GPCR), plays important roles in our biological system while the exact mechanisms behind it are less known. To get insights of effects upon BRS3 activation, we utilized quantitative proteomics approach to explore dynamic protein profiling during stimulation by its ligand. At different time points after with surrogate agonist, overexpressed HEK 293 cells (HEK 293-BRS3) was analyzed nano-LC-MS/MS. In total, 1593 cellular proteins...

Bombesin receptor subtype-3 (BRS3) is an orphan G-protein coupled (GPCR) that involved in a variety of pathological and physiological processes, while its biological functions underlying regulatory mechanisms remain largely unknown. In this study, quantitative phosphoproteomics approach was employed to comprehensively decipher the signal transductions occurred upon intracellular BRS3 activation. The lung cancer cell line H1299-BRS3 treated with MK-5046, agonist BRS3, for different durations....

Bombesin receptor subtype 3 (BRS-3) is a GPCR that expressed in the CNS, peripheral tissues, and tumors. Our understanding of BRS-3's role physiology pathophysiology limited because its natural ligand unknown. In an attempt to identify this ligand, we screened toad skin (Bufo bufo gargarizans Cantor) extracts identified prostaglandins as putative ligands. BRS-3–transfected human embryonic kidney (HEK) cells, found prostaglandins, with prostaglandin E2 (PGE2) being most potent, fulfill...

The objective of our present work was to explore the possible enhanced anti-neuroinflammatory ability Aspergillus oryzae fermented hemp seed in lipopolysaccharide (LPS)-stimulated N9 microglial cells and elucidate its underlying mechanism. water extract by oryzae. LPS-stimulated were employed for inflammatory cell model. release nitric oxide (NO) determined Griess assay. cytokines mediator expression measured qPCR ELISA. phosphorylated key signaling proteins, including nuclear factor-κB...

The mechanism underlying the crosstalk between Gαq-coupled bombesin receptor subtype-3 (BRS3) and Gαi-coupled E-prostanoid 3 (EP3) remains unknown. Here, we report that BRS3 EP3 form dimers in membrane of living HEK-293T cells. BRS3-EP3 switched to couple Gαs protein upon PGE2 stimulation, which provoked cAMP accumulation enhanced P38 phosphorylation. Quantitative proteomics analysis revealed activation was associated with cell migration. B16 melanoma line, endogenously expresses EP3,...

Abstract Background and Aims Renal fibrosis (RF) being the most important pathological change in progression of CKD, is currently assessed by evaluation a biopsy. This present study aimed to apply novel functional MRI (fMRI) protocol named amide proton transfer weighting (APTw) evaluate RF non-invasively. Method Male Sprague-Dawley (SD) rats were initially subjected bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction (UUO) Sham operation, respectively. All...

Bombesin receptor subtype-3(BRS-3) is an orphan in the bombesin family. Its signal transduction mechanism and biological function have attracted much attention. Seeking ligand for BRS-3 of great significance exploring its function. Considering fact that activation can induce change intracellular Ca~(2+) concentration, fluo-rometric imaging plate reader(FLIPR) was utilized screening at cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine Corydalis...