Search results for "Pathway"
showing 10 items of 1685 documents
Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1/CX3CR1 axis.
2014
Aims Insulin resistance (IR) is a major risk factor for cardiovascular disease and atherosclerosis. Life-threatening acute events are mainly due to rupture of unstable plaques, and the role of vascular smooth muscle cells (VSMCs) in this process in IR, Type 2 diabetes mellitus, and metabolic syndrome (T2DM/MetS) has not been fully addressed. Therefore, the role of VSMC survival in the generation of unstable plaques in T2DM/MetS and the involvement of inflammatory mediators was investigated. Methods and results Defective insulin receptor substrate 2 (IRS2)-mediated signalling produced insulin-resistant VSMCs with reduced survival, migration, and higher apoptosis than control cells. Silencing…
Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam
2013
The control of organ growth is a fundamental aspect of animal development but remains poorly understood. The morphogen Dpp has long been considered as a general promoter of cell proliferation during Drosophila wing development. It is an ongoing debate whether the Dpp gradient is required for the uniform cell proliferation observed in the wing imaginal disc. Here, we investigated how the Dpp signaling pathway regulates proliferation during wing development. By systematic manipulation of Dpp signaling we observed that it controls proliferation in a region-specific manner: Dpp, via omb, promoted proliferation in the lateral and repressed proliferation in the medial wing disc. Omb controlled th…
Lipid Activates mTORC1 and mTORC2 in the Absorption of Dietary Triglycerides
2018
Mechanistic target of rapamycin (mTOR) senses amino acids; however, its role in lipid metabolism is less established. Organismal lipid requirements are largely met through dietary intake. How nutrient sensing mechanisms in gut interface with dietary fat remains unclear. Here we reveal fundamental and cooperative roles for mTOR complexes 1 and 2 (mTORC1/2) in absorption of dietary triglycerides. Dietary lipid activates mTORC1/2 signaling in gut. Hyperactivating mTORC1 by deleting Tsc1 is sufficient to promote triglyceride absorption and metabolic disease in high fat-fed mice. Conversely, blocking mTORC1/2 by deleting Raptor or Rictor each decreases triglyceride absorption. Loss of Raptor seq…
OP0309 Intestinal sclerostin/serotonin axis is modulated by dysbiosis and regulates ilc3 expansion in as patients
2017
Background Sclerostin is an osteocyte-specific factor that binds to low-density lipoprotein receptor-related protein 5 (LRP5) inhibiting the Wnt signaling pathway and possibly contributing to the pathogenesis of Ankylosing spondylitis (AS). Subclinical gut inflammation observed in AS patients is characterized by the presence of dysbiosis and innate immune alterations. In the gut, LRP5 activation by unknown ligands inhibits serotonin production. Serotonin, by inducing glial derived neurotrophic factor (GDNF), controls ILC3 expansion, in the context of glial–ILC3–epithelial cell unit (GIECU). Sclerostin/serotonin axis has been never studied in AS. Objectives Aim of this study was to evaluate …
Neuronal immunoreactivity for mannose-binding lectin after venous occlusion-induced focal cerebral ischemia in rats
2012
Abstract A recent research reveals that complement activation exacerbates cerebral infarction. However, involvement of the lectin pathway, (the third complement activation pathway) in cerebral ischemia is not well studied. In this study, we investigated the appearance of mannose-binding lectin (MBL) in ischemic brain tissue. Male Wistar rats ( n = 25) were divided into three groups: untreated control, sham, and vein occlusion (VO). Rats in the VO group had two adjacent photochemically occluded cortical veins. Regional cerebral blood flow (rCBF) was measured in the sham and VO groups. Rats were perfusion-fixed at 72 h in the sham group and at 3, 24, and 72 h after inducing ischemia in the V…
The future: critical knowledge about anti-itch therapy.
2005
: Itch is an extremely frequent and enervating symptom of many diseases. Current anti-itch therapy, which is based almost exclusively on an “immunocentric” viewpoint, is often unsatisfactory. Recent studies show that this symptom is in fact the result of a complex interplay among skin, nervous system, endocrine system, and immune system. This explains the frequent failure of therapeutic strategies focused only on a single factor and suggests the usefulness of a polypharmacologic symptomatic treatment, designed on a case-by-case basis as a result of a multidisciplinary approach. We discuss the perspectives of anti-itch therapy in light of the new pathogenetic and pharmacologic acquisitions.
Mechanism of reperfusion damage after thrombolysis and ‘direct PTCA’
1997
Summary There is general agreement between cardiologists, that reperfusion of the infarct related coronary artery (PTCA) is the method of choice for the treatment of an acute myocardial infarction. However, the method utilized for inducing a rapid and complete reperfusion is still discussed. Even if thrombolysis will remain the method of choice for the major part of the population, part of the patient cohort with acute infarction will be treated by direct PTCA. Rapid reperfusion of ischemic myocardium reduces infarct size by limiting infarct extension into the entire area at risk, although a reperfusion damage is induced in the core ischemic area. This reperfusion damage has been convincing…
α-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Aβ generation
2009
The Swedish mutation within the amyloid precursor protein (APP) causes early-onset Alzheimer's disease due to increased cleavage of APP by BACE1. While beta-secretase shedding of Swedish APP (APPswe) largely results from an activity localized in the late secretory pathway, cleavage of wild-type APP occurs mainly in endocytic compartments. However, we show that liberation of Abeta from APPswe is still dependent on functional internalization from the cell surface. Inspite the unchanged overall beta-secretase cleaved soluble APP released from APP(swe) secretion, mutations of the APPswe internalization motif strongly reduced C99 levels and substantially decreased Abeta secretion. We point out t…
Poincaré surface profile. Novel non-invasive method to detect preferential ventricular response during atrial fibrillation
2007
The strategy of rate control during atrial fibrillation (AF) essentially deals with efforts to utilize and adjust the filtering properties of the atrioventricular (AV) node, allowing AF to continue and ensure that ventricular rate is controlled. In this work, a new tool based on the 3D Poincare plots is developed for the characterization of the ventricular response (VR) and the clinical evaluation of rate control therapies. Mechanisms underlying atrioventricular conduction during AF remain unclear. The role of the dual pathway AV nodal electrophysiology and the effects of the AV node modifications are still being an incognita. RR interval clusters exhibiting harmonic behaviour have been qua…
Early developmental alterations of low-Mg2+ -induced epileptiform activity in the intact corticohippocampal formation of the newborn mouse in vitro.
2005
Abstract The generation, propagation and pharmacological properties of low-Mg 2+ -induced epileptiform activity were examined in the intact corticohippocampal formation (CHF) of the newborn (P0–4) mouse in vitro. Multi-site field potential recordings in dentate gyrus (DG), CA3, CA1, entorhinal cortex (EC) and temporal cortex (TC) revealed in 0.2 mM Mg 2+ -containing ACSF a stable pattern of spontaneous epileptiform activity consisting of recurrent ictal-like events (ILEs) and interictal events (IEs). Although this activity could be consistently observed as early as P0, ILEs were smaller in amplitude, less frequent and showed a slower onset in P0–2 as compared to P3–4 animals. In all age gro…