KM-408, a novel phenoxyalkyl derivative as a potential anticonvulsant and analgesic compound for the treatment of neuropathic pain.

Background: Epilepsy frequently coexists with neuropathic pain. Our approach is based on the search for active compounds with multitarget profiles beneficial in terms of potential side effects and on the implementation of screening for potential multidirectional central activity.

Methods: Compounds were synthesized by means of chemical synthesis.

What is the ability of inflamed endothelium to uptake exogenous saturated fatty acids? A proof-of-concept study using spontaneous Raman, SRS and CARS microscopy.

Endothelial cells (EC) in vivo buffer and regulate the transfer of plasma fatty acid (FA) to the underlying tissues. We hypothesize that inflammation could alter the functionality of the EC, i.e.

Changes in the mitochondrial membrane potential in endothelial cells can be detected by Raman microscopy.

The role of mitochondria goes beyond their capacity to create molecular fuel and includes e.g. the production of reactive oxygen species and the regulation of cell death.

Sulfhemoglobin under the spotlight - Detection and characterization of SHb and HbFe-SH.

Sulfhemoglobinemia is an incurable disease caused by an overdose of sulfur-containing drugs with oxidizing properties. Its diagnosis remains hindered due to the similarity of symptoms to other pathological state - methemoglobinemia, as well as contradictory information on the structure and characteristics of sulfhemoglobin. Herein, we present sulfhemoglobinemia model on living functional human erythrocytes, designed to recreate processes which could take place in a patient body in order to complement missing information and highlight distinctiveness of two hemoglobin (Hb) adducts formed after interaction with sulfur donors.

Lipopolysaccharide affects energy metabolism and elevates nicotinamide N-methyltransferase level in human aortic endothelial cells (HAEC).

This study aimed to investigate the putative role of nicotinamide N-methyltransferase in the metabolic response of human aortic endothelial cells. This enzyme catalyses S-adenosylmethionine-mediated methylation of nicotinamide to methylnicotinamide. This reaction is accompanied by the reduction of the intracellular nicotinamide and S-adenosylmethionine content.

EdU sensing: The Raman way of following endothelial cell proliferation in vitro and ex vivo.

Endothelial cells line the lumen of all vessels in the body and maintain vascular homeostasis. In particular, endothelial cell regeneration in response to insult sustain functional endothelial layer. EdU (5-ethynyl-2'-deoxyuridine) is an alkyne-tagged proliferation probe that incorporates into newly synthesized DNA and is used for fluorescence imaging of cell proliferation with the use of "click chemistry" reaction with a fluorescent azide.

Chirality transfer observed in Raman optical activity spectra.

Chirality transfer (also called induced chirality) is a phenomenon present in chiroptical spectra that manifests itself as a new band or bands of an achiral molecule interacting with a chiral one. In the Raman optical activity (ROA) spectroscopy, the bands of achiral solvents have been recently observed, but the latest papers have shown that they corresponded to the new ECD-Raman (eCP-Raman) effect. Here, we show an unambiguous example of chirality transfer observed in the ROA spectra.

Dynamic Metabolic Changes During Prolonged Heart Perfusion Are Associated With Myocardial Functional Decline.

heart perfusion (ESHP) was developed to preserve and evaluate donated hearts in a perfused beating state. However, myocardial function declines during ESHP, which limits the duration of perfusion and the potential to expand the donor pool. In this research, we combine a novel, minimally-invasive sampling approach with comparative global metabolite profiling to evaluate changes in the metabolomic patterns associated with declines in myocardial function during ESHP.

Stimulated Raman scattering microscopy in chemistry and life science - Development, innovation, perspectives.

In this review, we present a summary of the basics of the Stimulated Raman Scattering (SRS) phenomenon, methods of detecting the signal, and collection of the SRS images. We demonstrate the advantages of SRS imaging, and recent developments, but also the limitations, especially in image capture speeds and spatial resolution. We also compare the use of SRS microscopy in biological system studies with other techniques such as fluorescence microscopy, second-harmonic generation (SHG)-based microscopy, coherent anti-Stokes Raman scattering (CARS), and spontaneous Raman, and we show the compatibility of SRS-based systems with other discussed methods.

Rac1 regulates lipid droplets formation, nanomechanical, and nanostructural changes induced by TNF in vascular endothelium in the isolated murine aorta.

Endothelial inflammation is recognized as a critical condition in the development of cardiovascular diseases. TNF-induced inflammation of endothelial cells is linked to the formation of lipid droplets, augmented cortical stiffness, and nanostructural endothelial plasma membrane remodelling, but the insight into the mechanism linking these responses is missing. In the present work, we determined the formation of lipid droplets (LDs), nanomechanical, and nanostructural responses in the model of TNF-activated vascular inflammation in the isolated murine aorta using Raman spectroscopy, fluorescence imaging, atomic force microscopy (AFM), and scanning electron microscopy (SEM).

From fixed-dried to wet-fixed to live - comparative super-resolution microscopy of liver sinusoidal endothelial cell fenestrations.

Fenestrations in liver sinusoidal endothelial cells (LSEC) are transcellular nanopores of 50-350 nm diameter that facilitate bidirectional transport of solutes and macromolecules between the bloodstream and the parenchyma of the liver. Liver diseases, ageing, and various substances such as nicotine or ethanol can negatively influence LSECs fenestrations and lead to defenestration. Over the years, the diameter of fenestrations remained the main challenge for imaging of LSEC .

Rapid shear stress-dependent ENaC membrane insertion is mediated by the endothelial glycocalyx and the mineralocorticoid receptor.

The contribution of the shear stress-sensitive epithelial Na channel (ENaC) to the mechanical properties of the endothelial cell surface under (patho)physiological conditions is unclear. This issue was addressed in in vivo and in vitro models for endothelial dysfunction. Cultured human umbilical vein endothelial cells (HUVEC) were exposed to laminar (LSS) or non-laminar shear stress (NLSS).

New chiral ECD-Raman spectroscopy of atropisomeric naphthalenediimides.

In this study, we found that a recently discovered ECD-Raman effect dominated over the natural Raman optical activity in a series of atropisomeric naphthalenediimides, and we investigated the kind of information about the molecular structure that could be obtained from the spectra. The ECD-Raman effect is polarised Raman scattering modulated by electronic circular dichroism. We showed that the spectra significantly depended on the substitution of the solute and/or the change of the solvent.

Direct Thrombin Inhibitor Dabigatran Compromises Pulmonary Endothelial Integrity in a Murine Model of Breast Cancer Metastasis to the Lungs; the Role of Platelets and Inflammation-Associated Haemostasis.

Activation of the coagulation cascade favours metastatic spread, but antithrombotic therapy might also have detrimental effects on cancer progression. In this study, we characterized the effects of dabigatran, a direct reversible thrombin inhibitor, on the pulmonary endothelial barrier and metastatic spread in a murine model of breast cancer metastasis. Dabigatran etexilate (100 mg kg) was administered to mice twice daily by oral gavage.

Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats.

Skeletal muscles are an important reservoir of nitric oxide (NO) stored in the form of nitrite [NO] and nitrate [NO] (NO). Nitrite, which can be reduced to NO under hypoxic and acidotic conditions, is considered a physiologically relevant, direct source of bioactive NO. The aim of the present study was to determine the basal levels of NO in striated muscles (including rat heart and locomotory muscles) with varied contents of tissue nitrite reductases, such as myoglobin and mitochondrial electron transport chain proteins (ETC-proteins).

Long-Term Effects of Aircraft Noise Exposure on Vascular Oxidative Stress, Endothelial Function and Blood Pressure: No Evidence for Adaptation or Tolerance Development.

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure.

Preservation of left ventricle peak and mean pulse flow blood velocity despite progressive deterioration of cardiac function in a chronic heart failure murine model.

The goal of this study was to assess the alterations in left ventricle (LV) blood flow velocity patterns in relation to progressive impairment of cardiac function in the course of heart failure (HF) in a unique murine model of chronic HF in Tgαq*44 mice. Doppler- and MRI-based assessments of blood velocity and cardiac performance, respectively, were performed in Tgαq*44 mice at the age of 1, 2, 4, 6, 8 and 12 months as compared with age-matched FVB control mice. One-month-old Tgαq*44 mice displayed elongated early diastolic phase with fully preserved cardiac function that, however, progressively deteriorated in older Tgαq*44 mice.

Raman and fluorescence imaging of phospholipidosis induced by cationic amphiphilic drugs in endothelial cells.

Cationic amphiphilic drugs (CADs) are known from lysosomotropism, drug-induced phospholipidosis (DIPL), activation of autophagy, and decreased cell viability, but the relationship between these events is not clear and little is known about DIPL in the endothelium. In this work, the effects of fluoxetine, amiodarone, clozapine, and risperidone on human microvascular endothelial cells (HMEC-1) were studied using a combined methodology of label-free Raman imaging and fluorescence staining. Raman spectroscopy was applied to characterize biochemical changes in lipid profile and their distribution in the cellular compartments, while fluorescence staining (LysoTracker, LipidTOX, LC3B, and JC-1) was used to analyze lysosome volume expansion, activation of autophagy, lipid accumulation, and mitochondrial membrane depolarization.

Prominent hypertrophy of perivascular adipocytes due to short-term high fat diet.

Excessive lipid accumulation is a serious problem in obesity leading to adipose tissue (AT) overgrowth, chronic inflammation, endothelial dysfunction, and elevated risk of cardiovascular complications. In this work, Raman techniques coupled with fluorescence imaging were applied to characterize the effects of short-term (2 weeks) and extended (up to 8 weeks) high-fat diet (HFD) feeding on various depots of the adipose tissue of young and mature mice. Our results proved the synergistic effect of age and HFD-induced obesity manifested by changes in the morphology of adipocytes and the chemical composition of lipids.

Simultaneous quantification of selected glycosaminoglycans by butanolysis-based derivatization and LC-SRM/MS analysis for assessing glycocalyx disruption in vitro and in vivo.

Glycosaminoglycans (GAGs) constitute the main building blocks of the endothelial glycocalyx (GLX), and disruption of GLX initiates and promotes endothelial dysfunction. Here, we aimed to develop a novel, specific and accurate LC-SRM/MS-based method for glycosaminoglycans (GAGs) profiling. The method involved butanolysis derivatization to facilitate GAG-specific disaccharide generation and its subsequent retention in LC-reversed-phase mode followed by mass spectrometric detection performed in positive ion-selected reaction monitoring (SRM) mode.