RANKL Is a Downstream Mediator for Insulin-Induced Osteoblastic Differentiation of Vascular Smooth Muscle Cells

Several reports have shown that circulating insulin level is positively correlated with arterial calcification; however, the relationship between insulin and arterial calcification remains controversial and the mechanism involved is still unclear. We used calcifying vascular smooth muscle cells (CVSMCs), a specific subpopulation of vascular smooth muscle cells that could spontaneously express osteoblastic phenotype genes and form calcification nodules, to investigate the effect of insulin on osteoblastic differentiation of CVSMCs and the cell signals involved. Our experiments demonstrated that insulin could promote alkaline phosphatase (ALP) activity, osteocalcin expression and the formation of mineralized nodules in CVSMCs. Suppression of receptor activator of nuclear factor κB ligand (RANKL) with small interfering RNA (siRNA) abolished the insulin-induced ALP activity. Insulin induced the activation of extracellular signal-regulated kinase (ERK)1/2, mitogen-activated protein kinase (MAPK) and RAC-alpha serine/threonine-protein kinase (Akt). Furthermore, pretreatment of human osteoblasts with the ERK1/2 inhibitor PD98059, but not the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, or the Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO), abolished the insulin-induced RANKL secretion and blocked the promoting effect of insulin on ALP activities of CVSMCs. Recombinant RANKL protein recovered the ALP activities decreased by RANKL siRNA in insulin-stimulated CVSMCs. These data demonstrated that insulin could promote osteoblastic differentiation of CVSMCs by increased RANKL expression through ERK1/2 activation, but not PI3K/Akt activation

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

A Longitudinal Study of the Association between the <i>LEPR</i> Polymorphism and Treatment Response in Patients with Bipolar Disorder

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment

Extracorporeal Membrane Oxygenation-assisted Cardiopulmonary Resuscitation for an In-hospital Cardiac Arrest Patient

Extracorporeal membrane oxygenation (ECMO) is used as a resuscitative tool for cardiogenic shock or cardiac arrest patients in the emergency department. It provides a better outcome for an in-hospital cardiac arrest (IHCA) patient, even if the patient has received prolonged cardiopulmonary resuscitation. We present the case of a 44-year-old female IHCA patient who presented to the emergency department with sudden onset of chest pain and cold sweating. Cardiac arrest occurred approximately 20 minutes after she arrived at the emergency department. Spontaneous heart beating returned immediately after cardiopulmonary resuscitation, and the patient was then supported by quickly applying ECMO. Thereafter, primary percutaneous transluminal coronary angioplasty was performed by a cardiologist. The patient received ECMO support for a total of 12 days. There were no major complications noted during the hospital stay. In conclusion, the use of ECMO to support cardiopulmonary function during cardiopulmonary resuscitation can improve the chance of survival in cases of IHCA that have better central nervous function after being weaned from ECMO. Shorter cardiopulmonary resuscitation duration and less organ damage may predict a better outcome in these patients