Sweeneyrytter0020
Gene set analysis showed an enrichment in extracellular organization and the PDGF (platelet-derived growth factor) signaling pathway. We found positive genetic correlations of cIMT with coronary artery disease
=0.21 (
=1.4×10
), peripheral artery disease
=0.45 (
=5.3×10
), and systolic blood pressure
=0.30 (
=4.0×10
). A negative genetic correlation between average of maximum cIMT and high-density lipoprotein was found
=-0.12 (
=7.0×10
).
Genome-wide association meta-analyses in >100 000 individuals identified 25 novel loci associated with cIMT providing insights into genes and tissue-specific regulatory mechanisms of proatherosclerotic processes. We found evidence for shared biological mechanisms with cardiovascular diseases.
100 000 individuals identified 25 novel loci associated with cIMT providing insights into genes and tissue-specific regulatory mechanisms of proatherosclerotic processes. We found evidence for shared biological mechanisms with cardiovascular diseases.
IGF-1 (insulin-like growth factor 1) exerts pleiotropic effects including promotion of cellular growth, differentiation, survival, and anabolism. We have shown that systemic IGF-1 administration reduced atherosclerosis in Apoe
(apolipoprotein E deficient) mice, and this effect was associated with a reduction in lesional macrophages and a decreased number of foam cells in the plaque. Almost all cell types secrete IGF-1, but the effect of macrophage-derived IGF-1 on the pathogenesis of atherosclerosis is poorly understood. We hypothesized that macrophage-derived IGF-1 will reduce atherosclerosis. Approach and Results We created macrophage-specific IGF-1 overexpressing mice on an Apoe
background. Macrophage-specific IGF-1 overexpression reduced plaque macrophages, foam cells, and atherosclerotic burden and promoted features of stable atherosclerotic plaque. Macrophage-specific IGF1 mice had a reduction in monocyte infiltration into plaque, decreased expression of CXCL12 (CXC chemokine ligand 12), and upregulation of ABCA1 (ATP-binding cassette transporter 1), a cholesterol efflux regulator, in atherosclerotic plaque and in peritoneal macrophages. Selleckchem GSK3 inhibitor IGF-1 prevented oxidized lipid-induced CXCL12 upregulation and foam cell formation in cultured THP-1 macrophages and increased lipid efflux. We also found an increase in cholesterol efflux in macrophage-specific IGF1-derived peritoneal macrophages.
Macrophage IGF-1 overexpression reduced atherosclerotic burden and increased features of plaque stability, likely via a reduction in CXCL12-mediated monocyte recruitment and an increase in ABCA1-dependent macrophage lipid efflux.
Macrophage IGF-1 overexpression reduced atherosclerotic burden and increased features of plaque stability, likely via a reduction in CXCL12-mediated monocyte recruitment and an increase in ABCA1-dependent macrophage lipid efflux.In this interview, Professor Gerd Pfeifer speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of DNA methylation. Dr. Pfeifer received a PhD degree from the University of Frankfurt, Germany. After postdoctoral work, he became a faculty member at the Beckman Research Institute of the City of Hope (Duarte, CA) in 1991. He is currently a full professor at the Van Andel Institute in Grand Rapids, MI. Dr. Pfeifer has served on several NIH advisory committees and has published over 300 research papers. Dr. Pfeifer's research interests are cancer etiology, molecular carcinogenesis and epigenetics. His expertise is in cellular and molecular biology. His lab currently works on epigenetic mechanisms of gene regulation in cancer and other diseases.miRNA-148b belongs to the family miR-148/-152, with significant differences in nonseed sequences, which can target diverse mRNA molecules. Reportedly, it may undergo deregulation in lung and ovarian cancers and downregulation in gastric, pancreatic and colon cancers. However, there is a need for further studies to better characterize its mechanism of action and in different types of cancer. In this review, we focus on the aberrant expression of miR-148b in different cancer types and highlight its main target genes and signaling pathways, as well as its pathophysiologic role and relevance to tumorigenesis in several types of cancer.Aim To evaluate the suitability of using aorta elastin scaffold, in combination with human adipose-derived mesenchymal stem cells (hAd-MSCs), as an approach for cardiovascular tissue engineering. Materials & Methods Human adipose-derived MSCs were seeded on elastin samples of decellularized bovine aorta. The samples were cultured in vitro to investigate the inductive effects of this scaffold on the cells. The results were evaluated using histological, and immunohistochemical methods, as well as MTT assay, DNA content, reverse transcription-PCR and scanning electron microscopy. Results Histological staining and DNA content confirmed the efficacy of decellularization procedure (82% DNA removal). MTT assay showed the construct's ability to support cell viability and proliferation. Cell differentiation was confirmed by reverse transcription-PCR and positive immunohistochemistry for alfa smooth muscle actin and von Willebrand. Conclusion The prepared aortic elastin samples act as a potential scaffold, in combination with MSCs, for applications in cardiovascular tissue engineering. Further experiments in animal models are required to confirm this.Nalfurafine is a G-protein-biased KOR (kappa opioid receptor) agonist that produces analgesia and lacks central nervous system adverse effects. Here, we examined the cardiovascular and renal responses to intravenous and oral nalfurafine alone and in combination with furosemide, hydrochlorothiazide, or amiloride. We hypothesized that nalfurafine, given its distinct mechanism of vasopressin inhibition, would increase urine output to these diuretics and limit electrolyte loss. Following catheterization, conscious Sprague-Dawley rats received an isotonic saline infusion and were then administered an intravenous bolus of nalfurafine, a diuretic, or a combination. Mean arterial pressure, heart rate, and urine output were recorded for 90 minutes. In another study, rats were placed in metabolic cages and administered drug in an oral volume load. Hourly urine samples were then collected for 5 hours. Intravenous and oral nalfurafine produced a marked diuresis, antinatriuresis, antikaliuresis, and a decrease in mean arterial pressure. Compared with diuretic treatment alone, intravenous coadministration with nalfurafine significantly increased urine output to furosemide and hydrochlorothiazide and decreased sodium and potassium excretion. Notably, mean arterial pressure was reduced with nalfurafine/diuretic combination therapy compared to diuretics alone. Similarly, oral coadministration of nalfurafine significantly increased urine output to hydrochlorothiazide and decreased sodium and potassium excretion, whereas combination with furosemide only limited the amount of sodium excreted. Further, both intravenous and oral coadministration of nalfurafine enhanced the diuresis to amiloride and decreased sodium excretion. Together, these findings demonstrate that nalfurafine enhances the diuresis to standard-of-care diuretics without causing an excessive loss of electrolytes, offering a new approach to treat several cardiovascular conditions.We present the case of a 37-year-old male who admitted to our hospital with fever, weakness, limb pain for 6 days and dyspnea for 14 hours .The patient had no immune related diseases.He was rapidly diagnosed with fulminant myocarditis and progressed to severe cardiogenic shock during the early stage.Then he was treated with V-A extracorporeal membrane oxygenation (ECMO). It is worth mentioning that the patient's peripheral blood was taken for metagenomic Next-Generation Sequencing(mNGS) upon admission and the results did not find any pathogenic bacteria.But there is no further examination(such as coronary angiography and myocardial biopsy) to determine the etiology of myocarditis.We present the case of a 71-years-old male with a history of pulmonary adenocarcinoma with palliative treatment. He was admitted to our hospital with hematochezia and anemia (Hemoglobin 10.6 g/dl).Environmental and ecological factors can trigger changes in the acoustic repertoire of cetaceans. This study documents the first use of a well-established passive acoustic monitoring device (C-POD) to analyze echolocation sounds and behavior of franciscana dolphins in different habitats estuary [Babitonga Bay (BB)] and open sea [Itapirubá Beach (IB)]. A total of 10 924 click trains were recorded in BB and 6 093 in IB. An inter-click interval less then 10 ms (so called "feeding buzzes") was used as a proxy for foraging activity. The main difference in the acoustic parameters between the two habitats was related to the frequency spectrum, with higher maximum and lower modal and minimum click frequencies in BB, and a train frequency range of 17 kHz, against 10 kHz in IB. Also, the click emission rate (clicks/s) was almost 20% higher in BB. Both studied habitats showed a high proportion of feeding buzzes (BB = 68%; IB = 58%), but with a higher probability of occurrence in BB (p less then 0.001) and at night (p less then 0.001) in both habitats. The C-PODs showed great potential to monitor occurrence, bioacoustics parameters, and echolocation behavior of franciscana dolphins. Longer-term temporal and spatial monitoring are necessary for elucidating several issues raised in this study.The occlusion effect (OE) refers to the phenomenon that more bone-conducted physiological sounds are transmitted into the earcanal when it is blocked and may cause discomfort on users of hearing protection devices. Models have been proposed to study the OE as they can help understand the physical mechanisms and can be used to evaluate the individual contribution on the OE of the factors that may affect it (i.e., occlusion device, ear anatomy, and stimulation). The existing finite element models developed to study the OE are limited by their truncated ear geometries. In order to progress in the understanding of the OE, the goal of this paper is to develop a finite element model of an entire head to predict the sound pressure field in its earcanals, open or occluded by earplugs. The model is evaluated by comparing the computed input mechanical impedances and OEs in various configurations with literature data. It is able to reproduce common behavior of the OE reported in the literature. In addition, the model is used to assess the effects on the simulated OEs of several parameters, including the modeling of the external air, the boundary condition at the head base and the material properties.Acoustic line transect surveys are often used in combination with visual methods to estimate the abundance of marine mammal populations. These surveys typically use towed linear hydrophone arrays and estimate the time differences of arrival (TDOAs) of the signal of interest between the pairs of hydrophones. The signal source TDOAs or bearings are then tracked through time to estimate the animal position, often manually. The process of estimating TDOAs from data and tracking them through time can be especially challenging in the presence of multiple acoustically active sources, missed detections, and clutter (false TDOAs). This study proposes a multi-target tracking method to automate TDOA tracking. The problem formulation is based on the Gaussian mixture probability hypothesis density filter and includes multiple sources, source appearance and disappearance, missed detections, and false alarms. It is shown that by using an extended measurement model and combining measurements from broadband echolocation clicks and narrowband whistles, more information can be extracted from the acoustic encounters.
