An adenosinergic positive feedback loop extends pharmacological cardioprotection duration.

Background And Purpose: Adenosine receptor activation induces delayed, sustained cardioprotection against ischaemia-reperfusion (IR) injury (24-72 h), but the mechanisms underlying extended cardioprotection duration remain unresolved. We hypothesized that a positive feedback loop involving adenosine receptor-induced proteasomal degradation of adenosine kinase (ADK) and decreased myocardial adenosine metabolism extends the duration of cardioprotection.

Experimental Approach: Mice were administered an ADK inhibitor, ABT-702, to induce endogenous adenosine signalling.

Varied effects of tobacco smoke and e-cigarette vapor suggest that nicotine does not affect endothelium-dependent relaxation and nitric oxide signaling.

Chronic smoking causes dysfunction of vascular endothelial cells, evident as a reduction of flow-mediated dilation in smokers, but the role of nicotine is still controversial. Given the increasing use of e-cigarettes and other nicotine products, it appears essential to clarify this issue. We studied extracts from cigarette smoke (CSE) and vapor from e-cigarettes (EVE) and heated tobacco (HTE) for their effects on vascular relaxation, endothelial nitric oxide signaling, and the activity of soluble guanylyl cyclase.

Lipopolysaccharide-induced sepsis impairs M2R-GIRK signaling in the mouse sinoatrial node.

Sepsis has emerged as a global health burden associated with multiple organ dysfunction and 20% mortality rate in patients. Numerous clinical studies over the past two decades have correlated the disease severity and mortality in septic patients with impaired heart rate variability (HRV), as a consequence of impaired chronotropic response of sinoatrial node (SAN) pacemaker activity to vagal/parasympathetic stimulation. However, the molecular mechanism(s) downstream to parasympathetic inputs have not been investigated yet in sepsis, particularly in the SAN.

Influence of Contour Scan Variation on Surface, Bulk and Mechanical Properties of LPBF-Processed AlSi7Mg0.6.

Metal additive manufacturing technologies have great potential for future use in load-bearing aerospace applications, requiring a deeper understanding of mechanical performance and influencing factors. The objective of this study was to investigate the influence of contour scan variation on surface quality, tensile and fatigue strength for laser powder bed fusion samples made of AlSi7Mg0.6 material and to create high-quality as-built surfaces.

Heat Accumulation-Induced Surface Structures at High Degrees of Laser Pulse Overlap on Ti6Al4V Surfaces by Femtosecond Laser Texturing.

In this work, femtosecond laser pulses at high repetition rates were used to fabricate unique microstructures on the surface of Ti6Al4V. We investigated the influence of pulse overlap and laser repetition rates on structure formation. Laser texturing with a high degree of overlap resulted in melting of the material, leading to the formation of specific microstructures that can be used as cavities for drug delivery.

Polysulfides derived from the hydrogen sulfide and persulfide donor P* inhibit IL-1β-mediated inducible nitric oxide synthase signaling in ATDC5 cells: are CCAAT/enhancer-binding proteins β and δ involved in the anti-inflammatory effects of hydrogen sulfide and polysulfides?

Hydrogen sulfide (HS) emerged as an essential signaling molecule exerting beneficial effects in various cardiovascular, neurodegenerative, or musculoskeletal diseases with an inflammatory component, such as osteoarthritis. These protective effects were initially attributed to protein S-sulfhydration, a posttranslational modification of reactive cysteine residues. However, recent studies suggest that polysulfides and not HS are responsible for S-sulfhydration.

Adenosine kinase (ADK) inhibition with ABT-702 induces ADK protein degradation and a distinct form of sustained cardioprotection.

Pharmacological inhibition of adenosine kinase (ADK), the major route of myocardial adenosine metabolism, can elicit acute cardioprotection against ischemia-reperfusion (IR) by increasing adenosine signaling. Here, we identified a novel, extended effect of the ADK inhibitor, ABT-702, on cardiac ADK protein longevity and investigated its impact on sustained adenosinergic cardioprotection. We found that ABT-702 treatment significantly reduced cardiac ADK protein content in mice 24-72 h after administration (IP or oral).

Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling.

Hydrogen sulfide (HS) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of HS, per-/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of HS.

A Comprehensive Study about the Role of Crosslink Density on the Tribological Behavior of DLC Coated Rubber.

The friction and wear behavior of coated rubber components is strongly dependent on the substrate properties. This work deals with the impact of the crosslink density, i.e.

Carbon, Glass and Basalt Fiber Reinforced Polybenzoxazine: The Effects of Fiber Reinforcement on Mechanical, Fire, Smoke and Toxicity Properties.

Bisphenol F and aniline-based benzoxazine monomers were selected to fabricate basalt, glass and carbon fiber reinforced polybenzoxazine via vacuum infusion, respectively. The impacts of the type of fiber reinforcement on the resulting material properties of the fiber reinforced polymers (FRPs) were studied. FRPs exhibited a homogenous morphology with completely impregnated fibers and near-zero porosity.

Author Correction: S-nitrosoglutathione inhibits adipogenesis in 3T3-L1 preadipocytes by S-nitrosation of CCAAT/enhancer-binding protein β.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Influence of Embedding Fiber Optical Sensors in CFRP Film Adhesive Joints on Bond Strength.

The increasing utilization of carbon fiber reinforced plastic (CFRP) in the aeronautical industry calls for a structural health monitoring (SHM) system for adhesively bonded CFRP joints. Optical glass fiber with inscribed fiber Bragg gratings (FBGs) is a promising technology for a SHM system. This paper investigates the intrusive effect of embedding optical glass fibers carrying FBGs on adhesive bond strength and adhesive layer thickness and quality.

Identifying potential targets for prevention and treatment of amyotrophic lateral sclerosis based on a screen of medicare prescription drugs.

: Few well-established factors are associated with risk of amyotrophic lateral sclerosis (ALS). We comprehensively evaluate prescription drugs use in administrative health claims from U.S.

S-nitrosoglutathione inhibits adipogenesis in 3T3-L1 preadipocytes by S-nitrosation of CCAAT/enhancer-binding protein β.

Murine 3T3-L1 adipocytes share many similarities with primary fat cells and represent a reliable in vitro model of adipogenesis. The aim of this study was to probe the effect of S-nitrosoglutathione (GSNO) on adipocyte differentiation. Adipogenesis was induced with a mixture of insulin, dexamethasone, and 3-isobutyl-1-methylxanthine in the absence and presence of increasing GSNO concentrations.

Effects of flavoring compounds used in electronic cigarette refill liquids on endothelial and vascular function.

Electronic cigarette refill liquids are commercially provided with a wide variety of flavoring agents. A recent study suggested that several common flavors may scavenge nitric oxide (NO) and cause endothelial dysfunction. It was the aim of the present study to investigate the effects of these flavors on NO/cyclic GMP-mediated signaling and vascular relaxation.

Site and mechanism of uncoupling of nitric-oxide synthase: Uncoupling by monomerization and other misconceptions.

Nitric oxide synthase (NOS) catalyzes the transformation of l-arginine, molecular oxygen (O), and NADPH-derived electrons to nitric oxide (NO) and l-citrulline. Under some conditions, however, NOS catalyzes the reduction of O to superoxide (O) instead, a phenomenon that is generally referred to as uncoupling. In principle, both the heme in the oxygenase domain and the flavins in the reductase domain could catalyze O formation.

Adenosine kinase attenuates cardiomyocyte microtubule stabilization and protects against pressure overload-induced hypertrophy and LV dysfunction.

Adenosine exerts numerous protective actions in the heart, including attenuation of cardiac hypertrophy. Adenosine kinase (ADK) converts adenosine to adenosine monophosphate (AMP) and is the major route of myocardial adenosine metabolism, however, the impact of ADK activity on cardiac structure and function is unknown. To examine the role of ADK in cardiac homeostasis and adaptation to stress, conditional cardiomyocyte specific ADK knockout mice (cADK) were produced using the MerCreMer-lox-P system.

Modulation of nitric oxide-stimulated soluble guanylyl cyclase activity by cytoskeleton-associated proteins in vascular smooth muscle.

Soluble guanylyl cyclase (sGC, EC 4.6.1.

Biomarker panels for characterizing microbial community biofilm formation as composite molecular process.

Microbial consortia execute collaborative molecular processes with contributions from individual species, on such basis enabling optimized molecular function. Such collaboration and synergies benefit metabolic flux specifically in extreme environmental conditions as seen in acid mine drainage, with biofilms as relevant microenvironment. However, knowledge about community species composition is not sufficient for deducing presence and efficiency of composite molecular function.

Sustained Formation of Nitroglycerin-Derived Nitric Oxide by Aldehyde Dehydrogenase-2 in Vascular Smooth Muscle without Added Reductants: Implications for the Development of Nitrate Tolerance.

According to current views, oxidation of aldehyde dehydrogenase-2 (ALDH2) during glyceryltrinitrate (GTN) biotransformation is essentially involved in vascular nitrate tolerance and explains the dependence of this reaction on added thiols. Using a novel fluorescent intracellular nitric oxide (NO) probe expressed in vascular smooth muscle cells (VSMCs), we observed ALDH2-catalyzed formation of NO from GTN in the presence of exogenously added dithiothreitol (DTT), whereas only a short burst of NO, corresponding to a single turnover of ALDH2, occurred in the absence of DTT. This short burst of NO associated with oxidation of the reactive C302 residue in the active site was followed by formation of low-nanomolar NO, even without added DTT, indicating slow recovery of ALDH2 activity by an endogenous reductant.

Irreversible Activation and Stabilization of Soluble Guanylate Cyclase by the Protoporphyrin IX Mimetic Cinaciguat.

Belonging to the class of so-called soluble guanylate cyclase (sGC) activators, cinaciguat and BAY 60-2770 are interesting therapeutic tools for the treatment of various cardiovascular pathologies. The drugs are supposed to preferentially stimulate oxidized or heme-depleted, but not native sGC. Since this concept has been challenged by studies demonstrating complete relaxation of nondiseased vessels, this study was designed to reinvestigate the mode of action in greater detail.

Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells.

The members of the nitric oxide synthase (NOS) family, eNOS, nNOS and iNOS, are well-characterized enzymes. However, due to the lack of suitable direct NO sensors, little is known about the kinetic properties of cellular NO generation by the different nitric oxide synthase isoenzymes. Very recently, we developed a novel class of fluorescent protein-based NO-probes, the geNOps, which allow real-time measurement of cellular NO generation and fluctuation.

Dipeptidyl peptidase-4 independent cardiac dysfunction links saxagliptin to heart failure.

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca-ATPase 2a axis and Na-Ca exchanger function in Ca extrusion.