In this review, we will provide an overview about signaling pathways and molecules that regulate the activity of beta-cell M3Rs. We will also discuss a novel pharmacological strategy to stimulate the activity of these receptors to reduce the metabolic impairments associated with T2D. Published by Elsevier B.V.BACKGROUND Acute kidney injury (AKI) is the main complication of crush syndrome (CS), and it is also a cause of lethality in CS. However, effective treatments for AKI are still lacking. Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor extracted from human urine that reportedly modulates innate immunity and pro-inflammatory responses in sepsis. Here, we explored the effect and the potential mechanism of ulinastatin on crush syndrome-induced acute kidney injury (CSAKI). METHODS A CSAKI rat model was established by using a digital crush injury device platform. Forty-six male Wistar rats were randomly divided into five groups the normal control (n = 6), CSAKI model (n = 10), CSAKI plus UTI1 (50,000 U/kg) (n = 10), CSAKI plus UTI2 (100,000 U/kg) (n = 10) and CSAKI plus UTI3 (200,000 U/kg) (n = 10) groups. Hematoxylin-eosin (HE) staining was used to investigate the reliability of the CSAKI model. The percentage of Th17/Treg lymphocytes in peripheral blood was measured by flow cytometry, and the expren of IL-17 compared with those of the CSAKI group. CONCLUSION The findings of our study indicate that UTI attenuates CS-induced AKI and alleviate the inflammatory response during the early stage. The mechanism of UTI may be due to regulating the balance between Th17/Treg cells. Our study provides a new mechanism for the beneficial effect of ulinastatin on CSAKI. V.While imiquimod (IMQ) has been widely used in dermatology, its side effect manifested as dermatitis couldn't be ignored. However, the underlying mechanism has not been fully understood. Considering the clinical features of IMQ-related dermatitis similar to pseudo-allergic reaction and the presence of large numbers of mast cell in tissues treated with IMQ, the possibility that IMQ-related dermatitis mediated by mast cell-specific Mas-related G protein-coupled receptor X2 (MRGPRX2) should be addressed.  https://www.selleckchem.com/products/tegatrabetan.html  To investigate the role of MRGPRX2 in vivo, MrgprB2, the mice homology of human MRGPRX2, was detected in IMQ-induced dermatitis mouse model. Histopathological changes including mast cell degranulation and footpad swelling were assayed in wild-type and MrgprB2-/- mice. The results showed that IMQ application induced dermatitis and footpad swelling with inflammatory cells infiltration plus mast cell activation in the skin of wild-type mice but reduced significantly in MrgprB2-/- mice. Further, compared to wild-type mice, serum histamine and inflammatory cytokine levels were compromised in MrgprB2-/- mice treated with IMQ, while the serum IgE level didn't change significantly. In vitro studies, levels of mediators released from murine peritoneal mast cells (MPMCs) after IMQ treatment were increased in a dose-dependent manner, which were much mild in MPMCs from MrgprB2-/- mice. Intracellular Ca2+ concentration was increased in a dose dependent manner after IMQ treatment both in MrgprB2-HEK293 and MRGPRX2-HEK293 cells. Moreover, β-hexosaminidase released after IMQ treatment was blocked by siRNA directed at the MRGPRX2 receptor in LAD2 cells. In summary, MrgprB2 /MRGPRX2 mediate mast cell activation and participate in IMQ-related dermatitis. The activation of NLRP3 inflammasome and NF-κB pathway, associating with oxidativestress, have been implicated in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). NecroX-5 has been reported to exhibit theeffectsofanti-oxidation and anti-stress in various diseases. However, the role of NecroX-5 in ALI has not been explicitly demonstrated. The aim of this study was to explore the therapeutic effects and potential mechanism action of NecroX-5 on ALI. Here, we found that NecroX-5 pretreatment dramatically diminished the levels of IL-1β, IL-18 and ROS in in RAW264.7 cells challenged with LPS and ATP. Furthermore, NecroX-5 suppressed the activation of NLRP3 inflammasome and NF-κB signalpathway. In addition, NecroX-5 also inhibited the thioredoxin-interacting protein (TXNIP) expression. In vivo, NecroX-5 reduced the LPS-induced lung histopathological injury, the number of TUNEL-positive cells, lung wet/dry (W/D) ratio, levels of total protein and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) in mice. Additionally, LPS-induced upregulation of myeloperoxidase (MPO), ROS production and malondialdehyde (MDA) were inhibited by NecroX-5 administration. Thus, our results demonstrate that NecroX-5 protects against LPS-induced ALI by inhibiting TXNIP/NLRP3 and NF-κB. V.Ischemia reperfusion injury (IRI) is a major challenge for renal transplantation. This study was performed to explore the mechanisms and potential molecular targets involved in renal IRI. In this study, the gene datasets GSE43974 and GSE126805 from the Gene Expression Omnibus database, which include ischemic and reperfused renal specimens, were analyzed to determine differentially expressed genes (DEGs). Gene ontology annotations, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed to determine the pathways that are significantly enriched during ischemia and reperfusion. We also determined the microenvironment cell types xCell and performed correlation analyses to reveal the relationship between the molecular pathways and microenvironment cell infiltration. We found 77 DEGs (76 up- and 1 downregulated) and 323 DEGs (312 up- and 11 downregulated) in the GSE43974 and GSE126805 datasets, respectively. Similar signaling pathway enrichment patterns were observed between the two datasets. The combined analyses demonstrate that the NOD-like receptor signaling pathway and its two downstream signaling pathways, MAPK and NF-kβ, are the major significantly enriched pathways. The xCell analysis identified immune cells that are significantly changed after reperfusion, including hematopoietic stem cells, M2 macrophages, monocytes, Treg cells, conventional dendritic cells, and pro B-cells. Enrichment scores of the NOD-like receptor signaling pathway and its downstream pathways during IRI was significantly correlated with the change levels in class-switched memory B-cell and hematopoietic stem cells in both datasets. These data reveal the important role of the NOD-like receptor signaling pathway during IRI, and the close relationship between this pathway and infiltration of specific immune cell types. Our data provide compelling insights into the pathogenesis and potential therapeutic targets for renal IRI.