Coronary angiogenesis during morphine and nicotine withdrawal in two-kidney one clip hypertensive (2K1C) rats

OBJECTIVE: This study was aimed to investigate the effects of addiction to nicotine and morphine and their withdrawal on coronary angiogenesis and serum NO concentrations in two-kidney one-clip hypertensive (2K1C) rats. METHODS: Male hypertensive rats were divided into the two below groups: Group (1): Rats received saline for 8 weeks (n = 8); Group (2): Rats received morphine and nicotine for 8 weeks (n = 32). At the end of 8 weeks, the groups (2) were divided into the four sub-groups, which three of them were treated with withdrawal drugs. Following treatments, blood pressure, heart rate, plasma renin activity (PRA), NO concentration and capillary density were measured. RESULTS: Results showed that blood pressure was signifi cantly reduced in the addicted group when compared to non-addicted (p <0.05). The withdrawal completely reversed blood pressure to the level observed pre-addiction (p <0.05). Coronary angiogenesis was signifi cantly lower in the addicted group in comparistion to normal (p <0.05) but withdrawal of addiction did not improve angiogenesis. CONCLUSION: On the basis of the present fi ndings, it may be indicative that the risk of cardiovascular complications in addiction is concurrent to chronic hypertension, which shows the importance of early diagnosis and treatment in clinical condition (Fig. 4, Ref. 59). Text in PDF www.elis.sk

Macrophage-Mediated Inflammation in Skin Wound Healing

Published: 21 September 2022Macrophages are key immune cells that respond to infections, and modulate pathophysiological conditions such as wound healing. By possessing phagocytic activities and through the secretion of cytokines and growth factors, macrophages are pivotal orchestrators of inflammation, fibrosis, and wound repair. Macrophages orchestrate the process of wound healing through the transitioning from predominantly pro-inflammatory (M1-like phenotypes), which present early post-injury, to anti-inflammatory (M2-like phenotypes), which appear later to modulate skin repair and wound closure. In this review, different cellular and molecular aspects of macrophage-mediated skin wound healing are discussed, alongside important aspects such as macrophage subtypes, metabolism, plasticity, and epigenetics. We also highlight previous studies demonstrating interactions between macrophages and these factors for optimal wound healing. Understanding and harnessing the activity and capability of macrophages may help to advance new approaches for improving healing of the skin.Alireza Hassanshahi, Mohammad Moradzad, Saman Ghalamkari, Moosa Fadaei, Allison J. Cowin and Mohammadhossein Hassanshah

Bone marrow sinusoidal endothelium as a facilitator/regulator of cell egress from the bone marrow

Despite more attention to cell migration from circulation into the bone marrow (BM), particularly homing of haematopoietic stem/progenitor cells, the process and mechanisms of cell mobilisation from the BM into the circulation remain largely underexplored. The process of cell mobilisation or transcellular cell migration from BM into the circulation (cell egress) is a crucial biological process in mammals as it is important to maintain homeostasis of various physiological functions including, but not limited to, the immune system, erythropoiesis, platelet release, and stem cell migration. The BM microvascular system composes of a monolayer of specialized endothelial cells, called sinusoidal endothelial cells (SECs). While it is very well evident that the process of cell egress occurs exclusively through BM SECs, there is a lack of systematic analyses addressing the extent of contribution of BM SECs to the process of cell egress from the BM. Therefore, this review aims to address the potential ability of BM SECs in regulating and/or facilitating the process of cell egress from BM. In this review, we address, firstly, the unique ultra-/structural and molecular features of BM SECs and discuss the possible biological interactions between BM SECs and various egressing cells in physiological conditions. Secondly, we propose the potential role of BM SECs in egress of leukemic cells from BM into the circulation. Finally, we discuss the potential role of BM SECs in homing of haematopoietic stem cells. Collectively, the current review suggests that the BM SECs may not be merely a neutral gatekeeper for cell intravasation and extravasation, but rather is a dynamic trafficking surveillance system, thereby the process of BM cell egress/mobilisation can be regulated

Therapeutic Targeting Notch2 Protects Bone Micro-Vasculatures from Methotrexate Chemotherapy-Induced Adverse Effects in Rats

Intensive cancer chemotherapy is well known to cause bone vasculature disfunction and damage, but the mechanism is poorly understood and there is a lack of treatment. Using a rat model of methotrexate (MTX) chemotherapy (five once-daily dosses at 0.75 mg/kg), this study investigated the roles of the Notch2 signalling pathway in MTX chemotherapy-induced bone micro-vasculature impairment. Gene expression, histological and micro-computed tomography (micro-CT) analyses revealed that MTX-induced micro-vasculature dilation and regression is associated with the induction of Notch2 activity in endothelial cells and increased production of inflammatory cytokine tumour necrosis factor alpha (TNFα) from osteoblasts (bone forming cells) and bone marrow cells. Blockade of Notch2 by a neutralising antibody ameliorated MTX adverse effects on bone micro-vasculature, both directly by supressing Notch2 signalling in endothelial cells and indirectly via reducing TNFα production. Furthermore, in vitro studies using rat bone marrow-derived endothelial cell revealed that MTX treatment induces Notch2/Hey1 pathway and negatively affects their ability in migration and tube formation, and Notch2 blockade can partially protect endothelial cell functions from MTX damage.Yaser Peymanfar, Yu-Wen Su, Mohammadhossein Hassanshahi and Cory J. Xia

LYSO based precision timing calorimeters

In this report we outline the study of the development of calorimeter detectors using bright scintillating crystals. We discuss how timing information with a precision of a few tens of pico seconds and below can significantly improve the reconstruction of the physics events under challenging high pileup conditions to be faced at the High-Luminosity LHC or a future hadron collider. The particular challenge in measuring the time of arrival of a high energy photon lies in the stochastic component of the distance of initial conversion and the size of the electromagnetic shower. We present studies and measurements from test beams for calorimeter based timing measurements to explore the ultimate timing precision achievable for high energy photons of 10 GeV and above. We focus on techniques to measure the timing with a high precision in association with the energy of the photon. We present test-beam studies and results on the timing performance and characterization of the time resolution of LYSO-based calorimeters. We demonstrate time resolution of 30 ps is achievable for a particular design

Constraints on sub-GeV dark-matter-electron scattering from the DarkSide-50 experiment

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOWe present new constraints on sub-GeV dark-matter particles scattering off electrons based on 6780.0 kg d of data collected with the DarkSide-50 dual-phase argon time projection chamber. This analysis uses electroluminescence signals due to ionized electrons extracted from the liquid argon target. The detector has a very high trigger probability for these signals, allowing for an analysis threshold of three extracted electrons, or approximately 0.05 keVee. We calculate the expected recoil spectra for dark matterelectron scattering in argon and, under the assumption of momentum-independent scattering, improve upon existing limits from XENON10 for dark-matter particles with masses between 30 and 100 MeV/c(2).1211117FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2016/09084-0Agências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling.

Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) or Salmonella Typhimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils. Increased release of BM lactate preferentially promotes neutrophil mobilization by reducing endothelial VE-Cadherin expression, increasing BM vascular permeability via endothelial lactate-receptor GPR81 signaling. GPR81-/- mice mobilize reduced levels of neutrophils in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection

Response of a CMS HGCAL silicon-pad electromagnetic calorimeter prototype to 20-300 GeV positrons

The Compact Muon Solenoid Collaboration is designing a new high-granularity endcap calorimeter, HGCAL, to be installed later this decade. As part of this development work, a prototype system was built, with an electromagnetic section consisting of 14 double-sided structures, providing 28 sampling layers. Each sampling layer has an hexagonal module, where a multipad large-area silicon sensor is glued between an electronics circuit board and a metal baseplate. The sensor pads of approximately 1 cm$^2$ are wire-bonded to the circuit board and are readout by custom integrated circuits. The prototype was extensively tested with beams at CERN's Super Proton Synchrotron in 2018. Based on the data collected with beams of positrons, with energies ranging from 20 to 300 GeV, measurements of the energy resolution and linearity, the position and angular resolutions, and the shower shapes are presented and compared to a detailed Geant4 simulation

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%