We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus (SLE). When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC) numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-kB phosphorylation. In human peripheral blood mononuclear cells (PBMCs), consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation. Cellular & Molecular Immunology
Aims:
To explore the molecular mechanism by which 17β-estradiol (estrogen 2, E2) regulates glucose transporter 2 (GLUT2) and insulin secretion in islet β cells through G protein-coupled estrogen receptor (GPER) via Akt/mTOR pathway.
Methods:
SPF-grade SD male rats were used to establish an
in vivo
type 2 diabetes model treated with E2. Rat insulinoma cells (INS-1) were cultured in normal or high glucose media with or without E2. Immunofluorescence double staining was used to detect GPER, GLUT2, insulin, and glucagon immunolocalization in rat islet tissues. Western blot was used to detect GPER, Akt, mTOR, and GLUT2 protein immunocontent. Real-time PCR detected Slc2a2 and glucose kinase (GK) content, and ELISA was used to detect insulin levels. Glucose uptake, GK activity and pyruvate dehydrogenase (PDH) activity were analyzed with glucose detection, GK activity and PDH activity assay kit.
Results:
Immunofluorescence double staining confocal indicated that E2 treatment up-regulated expression levels of GPER, GLUT2, and insulin, while down-regulated glucagon. Western blot results revealed E2 increased GPER, Akt/mTOR pathway, and GLUT2 protein immunocontent. Real-time PCR showed E2 elevated Slc2a2, GK content. Moreover, E2 improved insulin secretion, glucose uptake, GK activity, and PDH activity.
Conclusion:
Our findings indicated that exogenous E2 up-regulated GPER via the Akt/mTOR pathway to increase GLUT2 protein content and insulin secretion in islet β cells.
The Internet of Things (IOT) is considered to be the third wave of the world information industry after the computer and the Internet. In order to realize the ubiquitous access to the IOT, the cellular network can only be fused with the wireless sensor network physical social systems. Based on this, the purpose of this paper is to extract the general functions that necessary but unrelated with the specific application in the cellular network and wireless sensor fusion technology. These general functions, including terminal registration and serial number assignment, terminal authentication management, connection management, terminal fault management, terminal state management and monitoring, congestion control, terminal dormancy and activation, and so on. Aiming at these general functions, the author gives an exploratory solution to provide a referable shared function module for the fusion of cellular network and wireless sensor networks physical social systems. It is of great significance to improve the development progress of the IOT, reduce the difficulty and cost of development.INDEX TERMS Cellular network, fusion, the Internet of Things, wireless sensor network, physical social systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.