NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3)-Caspase-1 Inflammasome Degrades Contractile Proteins: Implications for Aortic Biomechanical Dysfunction and Aneurysm and Dissection Formation.
CONCLUSIONS: Inflammasome-caspase-1-mediated degradation of SMC contractile proteins may contribute to aortic biomechanical dysfunction and AAD development. This cascade may be a therapeutic target in AAD formation. In addition, glyburide may have protective effects against AAD development. PMID: 28153878 [PubMed - as supplied by publisher] (Source: Arteriosclerosis, Thrombosis and Vascular Biology)
Source: Arteriosclerosis, Thrombosis and Vascular Biology - February 1, 2017 Category: Cardiology Authors: Wu D, Ren P, Zheng Y, Zhang L, Xu G, Xie W, Lloyd EE, Zhang S, Zhang Q, Curci JA, Coselli JS, Milewicz DM, Shen YH, LeMaire SA Tags: Arterioscler Thromb Vasc Biol Source Type: research
Glucose elicits cephalic-phase insulin release in mice by activating K(ATP) channels in taste cells.
Abstract The taste of sugar elicits cephalic-phase insulin release (CPIR), which limits the rise in blood glucose associated with meals. Little is known, however, about the orosensory mechanisms that trigger CPIR. We asked whether oral stimulation with any of the following taste stimuli elicited CPIR in mice: glucose, sucrose, maltose, fructose, Polycose, saccharin, sucralose, AceK, SC45647 or a non-metabolizable sugar analog. The only taste stimuli that elicited CPIR were glucose and the glucose-containing saccharides (sucrose, maltose, Polycose). When we mixed an alpha-glucosidase inhibitor (acarbose) wi...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - January 31, 2017 Category: Physiology Authors: Glendinning JI, Frim YG, Hochman A, Lubitz GS, Basile AJ, Sclafani A Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research
Antidiabetic agents and cardiovascular outcomes in patients with heart diseases.
This article reviews evidence of benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Peer-reviewed articles were identified from MEDLINE and Current Content database (both 1966 to October 1, 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality,...
Source: Current Medical Research and Opinion - January 19, 2017 Category: Research Tags: Curr Med Res Opin Source Type: research
Sulfonylurea receptor-associated channels: Involvement in disease and therapeutic implications
The sulfonylurea receptors (SURs) 1 (SUR1) and 2 (SUR2) are members of the adenosine triphosphate (ATP) binding cassette transporters superfamily. Unlike other members of this superfamily, these receptors are not involved in transport but associate with pore-forming subunits to form cation channels. Both SUR1 and SUR2 associate with inward rectifying potassium (K+) (Kir) channels (Kir6) subunits to form functional ATP-sensitive K+ channels (KATP).1 These channels are molecular sensors that provide a link between cellular energy state and electrical excitability; they are tonically inhibited by ATP, and their activation in ...
Source: Neurology - January 15, 2017 Category: Neurology Authors: Benarroch, E. E. Tags: CLINICAL IMPLICATIONS OF NEUROSCIENCE RESEARCH Source Type: research
Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury.
Authors: Chen YL, Xu G, Liang X, Wei J, Luo J, Chen GN, Yan XD, Wen XP, Zhong M, Lv X Abstract Pyroptosis is a programmed cell death associated with caspase-1 and accompanied by the secretion of a large number of pro-inflammatory cytokines. In the acute stage of sepsis, the release of several pro-inflammatory cytokines aggravates hepatic cell death, and acute liver injury is aggravated with the progress of the disease, resulting in acute liver failure with a very high mortality rate. The present study investigated the effect of inhibiting hepatic cell pyroptosis on the septic acute liver injury. Septic acu...
Source: American Journal of Translational Research - January 13, 2017 Category: Research Tags: Am J Transl Res Source Type: research
Phosphatidylserine Outer Layer Translocation Is Implicated in IL-10 Secretion by Human Regulatory B Cells
This study showed that B10 cells have an increased PS exposure independently of any apoptotic state. B cells exposing PS differentiate more into B10 cells whereas PS blockage inhibits B10 cells generation. These results strongly suggest a link between PS exposure and B10 cells. (Source: PLoS One)
Source: PLoS One - January 9, 2017 Category: Biomedical Science Authors: Rachel Audo Source Type: research
oxLDL antibody inhibits MCP-1 release in monocytes/macrophages by regulating Ca(2+) /K(+) channel flow.
Abstract oxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP-1 release in monocytes/macrophages through their TLR-4 (Toll-like receptor 4) and ERK MAPK pathway and is calcium/potassium channel-dependent. Using blocking antibodies against CD36, TLR-4, SR-AI and LOX-1, only TLR-4 antibody was found to have an inhibitory effect and ERK MAPK-specific inhibitor (PD98059) was found to have a dramatic inhibitory effect compared...
Source: J Cell Mol Med - December 19, 2016 Category: Molecular Biology Authors: Su J, Zhou H, Liu X, Nilsson J, Fredrikson GN, Zhao M Tags: J Cell Mol Med Source Type: research
oxLDL antibody inhibits MCP ‐1 release in monocytes/macrophages by regulating Ca2+/K+ channel flow
Abstract oxLDL peptide vaccine and its antibody adoptive transferring have shown a significantly preventive or therapeutic effect in atherosclerotic animal model. The molecular mechanism behind this is obscure. Here, we report that oxLDL induces MCP‐1 release in monocytes/macrophages through their TLR‐4 (Toll‐like receptor 4) and ERK MAPK pathway and is calcium/potassium channel‐dependent. Using blocking antibodies against CD36, TLR‐4, SR‐AI and LOX‐1, only TLR‐4 antibody was found to have an inhibitory effect and ERK MAPK‐specific inhibitor (PD98059) was found to have a dramatic inhibitory effect compare...
Source: Journal of Cellular and Molecular Medicine - December 19, 2016 Category: Molecular Biology Authors: Jinyu Su, Hui Zhou, Xianyan Liu, Jan Nilsson, Gunilla Nordin Fredrikson, Ming Zhao Tags: Original Article Source Type: research
Lack of Evidence to Guide Deprescribing of Antihyperglycemics: A Systematic Review
ConclusionsThere is limited evidence available regarding deprescribing antihyperglycemic medications. Adequately powered, high-quality studies, particularly in the elderly and with clinically important outcomes, are required to support evidence-based decision-making.Protocol registration numberCRD42015017748. (Source: Diabetes Therapy)
Source: Diabetes Therapy - December 14, 2016 Category: Endocrinology Source Type: research
SHORT and LONG TERM EFFECTS of a DPP-4 INHIBITOR VERSUS BEDTIME NPH INSULIN as ADD-ON THERAPY in PATIENTS WITH TYPE 2 DIABETES.
CONCLUSION: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent improvement in alpha or beta cell function in patients with long-duration diabetes. PMID: 27928958 [PubMed - as supplied by publisher] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - December 7, 2016 Category: Drugs & Pharmacology Authors: da Silva GM, Nogueira KC, Fukui RT, Correia MR, Dos Santos RF, da Silva ME Tags: Curr Pharm Des Source Type: research
Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus
This article reviews the prevalence of obesity and T2DM in children and adolescents (youth). We then summarize published studies on safety and effectiveness of antihyperglycemic medications in youth. Drug disposition may be affected by age or puberty and thus the expression and activity of different pathways for drug metabolism and xenobiotic transporters are compared between youth and adults followed by a summary of pharmacokinetics studies of antihyperglycemic agents currently used in this population. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - November 9, 2016 Category: Drugs & Pharmacology Source Type: research
Statin protects the heart against ischemia-reperfusion injury via inhibition of the NLRP3 inflammasome
We have recently read with great interest the report by Toldo and co-workers  concerning “Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia–reperfusion in the mouse”. The authors revealed that the NLRP3 inhibitor 16,673–34-0, an intermediate substrate in the glyburide synthesis free of the cyclohexylurea moiety, attenuated the seco ndary inflammatory damage and infarct size following myocardial ischemia-reperfusion (I/R) in vivo, providing a novel therapeutic approach to reperfusion injury. (Source: International Journal of Cardiology)
Source: International Journal of Cardiology - November 8, 2016 Category: Cardiology Authors: Si-yang Yu, Liang Tang, Guo-jun Zhao, Sheng-hua Zhou Source Type: research
Fluorescence-based rapid measurement of sphingosine-1-phosphate transport activity in erythrocytes [Methods]
In this study, we attempted to establish a rapid and reliable method for measuring the S1P transport activity in erythrocytes by using a fluorescent S1P analog, 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD)-labeled S1P. NBD-S1P was released from erythrocytes in a time-dependent manner. The NBD-S1P release was reduced after exposure to glyburide, which is an inhibitor of the S1P transporter in erythrocytes. Moreover, the release of NBD-S1P and S1P from erythrocytes was competitively inhibited by intracellular S1P and NBD-S1P, respectively. These results showed that the erythrocyte S1P transporter exports NBD-S1P. We optimized the ...
Source: The Journal of Lipid Research - October 31, 2016 Category: Lipidology Authors: Kobayashi, N., Otsuka, M., Yamaguchi, A., Nishi, T. Tags: Methods Source Type: research
Mechanisms behind the protein aggregation ‐related inflammasome activation in RPE cells
ConclusionsOur results suggest that oxidative stress plays a role in the inflammasome activation in RPE cells upon declined intracellular clearance. (Source: Acta Ophthalmologica)
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: A. Kauppinen, N. Piippo, E. Korhonen, M. Hytti, K. Kinnunen, K. Kaarniranta Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps
In conclusion, NLRP3 inflammasome signaling pathway played a pro-inflammatory role in the pathogenesis of CRSwNP, especially in ECRSwNP. NLRP3 inflammasome signaling pathway was augmented by LPS, but suppressed by glyburide. (Source: Inflammation)
Source: Inflammation - September 9, 2016 Category: Allergy & Immunology Source Type: research