Immune mechanisms in heart failure Zhang, Yingying; Bauersachs, Johann; Langer, Harald F.
European journal of heart failure,
November 2017, Letnik:
19, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Elevated levels of circulating pro‐inflammatory biomarkers in patients with both ischaemic and non‐ischaemic heart failure (HF) correlate with disease severity and prognosis. Experimental studies ...have shown activation of immune response mechanisms in the heart to provoke cardiac adverse remodelling and cause left ventricular dysfunction. Consequently, most of the clinical trials targeting elements of the immune response in HF attempted to modulate the inflammatory response. Surprisingly, clinical studies targeting immune effectors were either neutral or even increased pre‐specified clinical endpoints, and some studies resulted in worsening of HF. This review discusses immune mediators involved in the pathogenesis and progression of HF and potential therapeutic applications targeting inflammation in HF. Besides more obvious settings featuring immune activation such as inflammatory or ischaemic cardiomyopathy, the relevance of immune activation in acute or chronic HF of other origins, including volume overload or valvular heart disease, is highlighted. Understanding how cell‐specific and molecular mechanisms of the immune response interfere with cardiac remodelling in HF may open new avenues to design biomarkers or druggable targets.
High-harmonic (HH) generation in crystalline solids marks an exciting development, with potential applications in high-efficiency attosecond sources, all-optical bandstructure reconstruction and ...quasiparticle collisions. Although the spectral and temporal shape of the HH intensity has been described microscopically, the properties of the underlying HH carrier wave have remained elusive. Here, we analyse the train of HH waveforms generated in a crystalline solid by consecutive half cycles of the same driving pulse. Extending the concept of frequency combs to optical clock rates, we show how the polarization and carrier-envelope phase (CEP) of HH pulses can be controlled by the crystal symmetry. For certain crystal directions, we can separate two orthogonally polarized HH combs mutually offset by the driving frequency to form a comb of even and odd harmonic orders. The corresponding CEP of successive pulses is constant or offset by pi , depending on the polarization. In the context of a quantum description of solids, we identify novel capabilities for polarization- and phase-shaping of HH waveforms that cannot be accessed with gaseous sources.
Complement, inflammation and thrombosis Rawish, Elias; Sauter, Manuela; Sauter, Reinhard ...
British journal of pharmacology,
July 2021, Letnik:
178, Številka:
14
Journal Article
Recenzirano
Odprti dostop
A mutual relationship exists between immune activation and mechanisms of thrombus formation. In particular, elements of the innate immune response such as the complement system can modulate platelet ...activation and subsequently thrombus formation. Several components of the complement system including C3 or the membrane attack complex have been reported to be associated with platelets and become functionally active in the micromilieu of platelet activation. The exact mechanisms how this interplay is regulated and its consequences for tissue inflammation, damage or recovery remain to be defined. This review addresses the current state of knowledge on this topic and puts it into context with diseases featuring both thrombosis and complement activation.
Linked Articles
This article is part of a themed issue on Canonical and non‐canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc
Ultrafast charge transport in strongly biased semiconductors is at the heart of high-speed electronics, electro-optics and fundamental solid-state physics. Intense light pulses in the terahertz ...spectral range have opened fascinating vistas. Because terahertz photon energies are far below typical electronic interband resonances, a stable electromagnetic waveform may serve as a precisely adjustable bias. Novel quantum phenomena have been anticipated for terahertz amplitudes, reaching atomic field strengths. We exploit controlled (multi-)terahertz waveforms with peak fields of 72 MV cm-1 to drive coherent interband polarization combined with dynamical Bloch oscillations in semiconducting gallium selenide. These dynamics entail the emission of phase-stable high-harmonic transients, covering the entire terahertz-to-visible spectral domain between 0.1 and 675 THz. Quantum interference of different ionization paths of accelerated charge carriers is controlled via the waveform of the driving field and explained by a quantum theory of inter- and intraband dynamics. Our results pave the way towards all-coherent terahertz-rate electronics.
•Cancer-associated thrombosis is a major health problem that affects morbidity and mortality of people with cancer.•Surgical and systemic pharmacological anticancer treatments have a significant ...impact on the thrombotic risk of patients.•Primary thromboprophylaxis may be considered in high-risk ambulatory cancer patients using validated risk models.•Anticoagulant treatment of VTE in cancer patients is effective but may be associated with increased bleeding.•LMWH or DOACs are effective treatments and generally safe options for cancer-associated thrombosis.
Beyond platelets function in hemostasis, there is emerging evidence to suggest that platelets contribute crucially to inflammation and immune responses. Therefore, considering the detrimental role of ...inflammatory conditions in severe neurological disorders such as multiple sclerosis or stroke, this review outlines platelets involvement in neuroinflammation. For this, distinct mechanisms of platelet-mediated thrombosis and inflammation are portrayed, focusing on the interaction of platelet receptors with other immune cells as well as brain endothelial cells. Furthermore, we draw attention to the intimate interplay between platelets and the complement system as well as between platelets and plasmatic coagulation factors in the course of neuroinflammation. Following the thorough exposition of preclinical approaches which aim at ameliorating disease severity after inducing experimental autoimmune encephalomyelitis (a counterpart of multiple sclerosis in mice) or brain ischemia-reperfusion injury, the clinical relevance of platelet-mediated neuroinflammation is addressed. Thus, current as well as future propitious translational and clinical strategies for the treatment of neuro-inflammatory diseases by affecting platelet function are illustrated, emphasizing that targeting platelet-mediated neuroinflammation could become an efficient adjunct therapy to mitigate disease severity of multiple sclerosis or stroke associated brain injury.
Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates
. Lightwave-driven currents have been assumed to be essential for high-harmonic ...generation in solids
, charge transport in nanostructures
, attosecond-streaking experiments
and atomic-resolution ultrafast microscopy
. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators
may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi
Te
. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.
Abstract
Computational study of molecules and materials from first principles is a cornerstone of physics, chemistry, and materials science, but limited by the cost of accurate and precise ...simulations. In settings involving many simulations, machine learning can reduce these costs, often by orders of magnitude, by interpolating between reference simulations. This requires representations that describe any molecule or material and support interpolation. We comprehensively review and discuss current representations and relations between them. For selected state-of-the-art representations, we compare energy predictions for organic molecules, binary alloys, and Al–Ga–In sesquioxides in numerical experiments controlled for data distribution, regression method, and hyper-parameter optimization.
P2X receptors belong to a family of cation channel proteins, which respond to extracellular adenosine 5′-triphosphate (ATP). These receptors have gained increasing attention in basic and ...translational research, as they are central to a variety of important pathophysiological processes such as the modulation of cardiovascular physiology, mediation of nociception, platelet and macrophage activation, or neuronal–glial integration. While P2X1 receptor activation is long known to drive platelet aggregation, P2X7 receptor antagonists have recently been reported to inhibit platelet activation. Considering the role of both P2X receptors and platelet-mediated inflammation in neuronal diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and stroke, targeting purinergic receptors may provide a valuable novel therapeutic approach in these diseases. Therefore, the present review illuminates the role of platelets and purinergic signaling in these neurological conditions to evaluate potential translational implications.
Platelets contribute to processes beyond thrombus formation and may play a so far underestimated role as an immune cell in various circumstances. This review outlines immune functions of platelets in ...host defense, but also how they may contribute to mechanisms of infectious diseases. A particular emphasis is placed on the interaction of platelets with other immune cells. Furthermore, this article outlines the features of atherosclerosis as an inflammatory vascular disease highlighting the role of platelet crosstalk with cellular and soluble factors involved in atheroprogression. Understanding, how platelets influence these processes of vascular remodeling will shed light on their role for tissue homeostasis beyond intravascular thrombosis. Finally, translational implications of platelet-mediated inflammation in atherosclerosis are discussed.
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