Interaction of Cyclosporin C with Dy Ions in Acetonitrile and in Complex with Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

The spectral characteristics of cyclosporin C (CsC) with the addition of Dy ions in acetonitrile (CDCN) and CsC with Dy incorporated into dodecylphosphocholine (DPC) micelle in deuterated water were investigated by high-resolution NMR spectroscopy. The study was focused on the interaction between Dy ions and CsC molecules in different environments. Using a combination of one-dimensional and two-dimensional NMR techniques, we obtained information on the spatial features of the peptide molecule and the interaction between CsC and the metal ion.

Novel Fluoroquinolones With Pinane Moiety: Synthesis and Antimicrobial Activity.

Here, we report a synthesis of fluoroquinolones carrying a monoterpene moiety at the C7 position of aromatic structure. The minimal inhibitory concentrations of fluoroquinolone fused with trans-3-hydroxy-cis-myrtanylamine 18 against Staphylococcus aureus (MSSA isolates) were two- to eightfold lower compared to moxifloxacin, although fourfold higher against MRSA isolates. The fluoroquinolone fused with (-)-nopylamine 16 was four- to eightfold less active on MSSA compared to moxifloxacin, while had similar activity on MRSA.

H, C, and N resonance assignments of the amyloidogenic peptide SEM2(49-107) by NMR spectroscopy.

It has been shown that human seminal fluid is a major factor in enhancing HIV activity. The SEM2(49-107) peptide is a product of cleavage after ejaculation by internal prostheses of the semenogelin 2 protein, expressed in seminal vesicles. It is established that the peptide SEM2(49-107) forms amyloid fibrils, which increase probability of contracting HIV infection.

Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage.

Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs).

Geroprotective effects of GdVO:Eu nanoparticles, metformin and calorie restriction in male rats with accelerated aging induced by overnutrition in early postnatal ontogenesis.

GdVO:Eu nanoparticles (OVNPs) have previously been shown to exhibit anti-aging effects in old rats.The accelerated aging model (overnutrition in early postnatal ontogenesis (POF)) was used to confirm the effect of OVNPs as a potential geroprotector. A comparative study of the effect of OVNPs, calorierestriction (CR) and CR-mimetic-metformin was carried out using a number of criteria: survival, prooxidant-antioxidant balance in the liver and blood, physiological parameters of male Wistar rats with accelerated aging.

Nanocrystalline cerium dioxide reduces recrystallization in cryopreservation solutions.

Nanocrystalline cerium dioxide is able to protect living cells from oxidative stress under the influence of various stress factors, in particular under the one of low temperatures. This study investigates the phase-structural transformations in aqueous solutions containing CeO nanoparticles (NPs) and their impact on the cryopreservation process. Differential scanning calorimetry and thermomechanical analysis were used to analyse the phase transitions in aqueous suspensions of CeO NPs and aqueous solutions of the cryoprotectant dimethyl sulfoxide (MeSO) with CeO NPs.

GdVO:Eu and LaVO:Eu Nanoparticles Exacerbate Oxidative Stress in L929 Cells: Potential Implications for Cancer Therapy.

The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO:Eu and LaVO:Eu nanoparticles, which have been already shown to have redox-active, anti-inflammatory, antibacterial, and wound healing properties, both in vitro and in vivo, worsen oxidative stress of L929 cells triggered by hydrogen peroxide or -butyl hydroperoxide (tBuOOH) at the concentrations that are safe for intact L929 cells. This effect was observed upon internalization of the investigated nanosized materials and is associated with the cleavage of caspase-3 and caspase-9 without recruitment of caspase-8.

A novel terpene-BODIPY conjugates based fluorescent probes: Synthesis, spectral properties, stability, penetration efficiency into bacterial, fungal and mammalian cells.

The design of fluorescent probes based on biocompatible luminophores for medical diagnostics is one of the rapidly developing areas worldwide. Here, we report the synthesis of a novel BODIPYs containing a propanoic acid residue at the α-position of one of the pyrrole rings conjugated to (+)-myrtenol or thiotherpenoid. Both conjugates are quite photostable (t ∼ 40 h) and exhibit high fluorescence efficiency (φ ∼ 77-90 %).

Calcium ions do not influence the Aβ(25-35) triggered morphological changes of lipid membranes.

We have studied the effect of calcium ions (Ca) at various concentrations on the structure of lipid vesicles in the presence of amyloid-beta peptide Aβ(25-35). In particular, we have investigated the influence of calcium ions on the formation of recently documented bicelle-like structures (BLSs) emerged as a result of Aβ(25-35) triggered membrane disintegration. First, we have shown by using small-angle X-ray and neutron scattering that peptide molecules rigidify the lipid bilayer of gel phase DPPC unilamellar vesicles (ULVs), while addition of the calcium ions to the system hinders this effect of Aβ(25-35).

NLRX1 Inhibits LPS-Induced Microglial Death via Inducing p62-Dependent HO-1 Expression, Inhibiting MLKL and Activating PARP-1.

The activation of microglia and the production of cytokines are key factors contributing to progressive neurodegeneration. Despite the well-recognized neuronal programmed cell death regulated by microglial activation, the death of microglia themselves is less investigated. Nucleotide-binding oligomerization domain, leucine-rich repeat-containing X1 (NLRX1) functions as a scaffolding protein and is involved in various central nervous system diseases.

Cis-trans isomerization in cyclosporin C dissolved in acetonitrile.

Cyclosporin is an 11-amino acid cyclic peptide with pharmacologically valuable properties which has a variety of actual and potential applications. Its activity relies on the cell membrane permeability which, in turn, depends on the structure of cyclosporin and its ability to change the conformation. In this work, conformational exchange processes occurring in cyclosporin C were studied using one- and two-dimensional nuclear magnetic resonance spectroscopy.

Arrangement of lipid vesicles and bicelle-like structures formed in the presence of Aβ(25-35) peptide.

Our complementary experimental data and molecular dynamics (MD) simulations results reveal the structure of previously observed lipid bicelle-like structures (BLSs) formed in the presence of amyloid-beta peptide Aβ(25-35) below the main phase transition temperature (T) of saturated phosphatidylcholine lipids and small unilamellar vesicles (SUVs) above this temperature. First, we show by using solid-state P nuclear magnetic resonance (NMR) spectroscopy that our BLSs being in the lipid gel phase demonstrate magnetic alignment along the magnetic field of NMR spectrometer and undergo a transition to SUVs in the lipid fluid phase when heated through the T. Secondly, thanks to the BLS alignment we present their lipid structure.

Extent of N-Terminus Folding of Semenogelin 1 Cleavage Product Determines Tendency to Amyloid Formation.

It is known that four peptide fragments of predominant protein in human semen Semenogelin 1 (SEM1) (SEM1(86-107), SEM1(68-107), SEM1(49-107) and SEM1(45-107)) are involved in fertilization and amyloid formation processes. In this work, the structure and dynamic behavior of SEM1(45-107) and SEM1(49-107) peptides and their N-domains were described. According to ThT fluorescence spectroscopy data, it was shown that the amyloid formation of SEM1(45-107) starts immediately after purification, which is not observed for SEM1(49-107).

3-Arylidene-2-oxindoles as GSK3β inhibitors and anti-thrombotic agents.

Development of novel agents that prevent thrombotic events is an urgent task considering increasing incidence of cardiovascular diseases and coagulopathies that accompany cancer and COVID-19. Enzymatic assay identified novel GSK3β inhibitors in a series of 3-arylidene-2-oxindole derivatives. Considering the putative role of GSK3β in platelet activation, the most active compounds were evaluated for antiplatelet activity and antithrombotic activity.

Rare-earth orthovanadate nanoparticles trigger Ca-dependent eryptosis.

. Rare-earth orthovanadate nanoparticles (ReVO:Eu, Re = Gd, Y or La) are promising agents for photodynamic therapy of cancer due to their modifiable redox properties. However, their toxicity limits their application.

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors.

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2.

Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

Design, Synthesis and Pharmacological Evaluation of Novel C,C-Quinoxaline Derivatives as Promising Anxiolytic Agents.

A new series of quinoxaline derivatives, -, were synthesized and their anxiolytic potential was evaluated in vivo using elevated plus maze (EPM), open field (OF) and light-dark box (LDB) techniques. According to the results of the EPM, four active compounds were found in , , , . Their anxiolytic properties were confirmed in terms of LDB and the most active was compound .

Antimicrobial activity and cytotoxicity study of cerium oxide nanoparticles with two different sizes.

The control over bacterial diseases requires the development of novel antibacterial agents. The use of antibacterial nanomedicines is one of the strategies to tackle antibiotic resistance. The study was designed to assess the antimicrobial activity of cerium oxide (CeO ) nanoparticles (NP) of two different sizes (CeO NP1 [1-2 nm] and CeO NP2 [10-12 nm]) and their cytotoxicity towards eukaryotic cells.