GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca²⁺, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.     

The influence of poly(3,4-ethylenedioxythiophene) modification on the transport properties and fuel cell performance of Nafion-117 membranes

Nafion-117/PEDOT composite membranes were synthesized by in situ chemical polymerization of 3,4-ethylenedioxythiophene (EDOT) using ammonium persulfate as an oxidant. The polymerization of EDOT in Nafion membranes for various EDOT/oxidant treatment sequences was studied for the first time. PEDOT introduction leads to a slight decrease in both the ion-exchange capacity and water uptake of the composite membranes, as well as to an increase in cationic transport. Membranes initially treated with an oxidant exhibit better conductivity and lower hydrogen permeability. The effect of both modification of Nafion-117 membranes by PEDOT and hot-pressing of hydrogen-oxygen membrane-electrode assemblies (MEAs) on the performance of proton-exchange membrane fuel cells was studied. The maximum power density of the fabricated MEAs increases 1.5-fold: from 510 (for a pristine Nafion-117 membrane) to 810 mW cm⁻² (for a membrane modified by PEDOT). The current density at a voltage of 0.4 V reaches 1248 and 2246 mA cm⁻², respectively.     

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.     

Role of Chiral Configuration in the Photoinduced Interaction of D- and L-Tryptophan with Optical Isomers of Ketoprofen in Linked Systems

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer’s and Parkinson’s diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor–acceptor dyad with (R)- and (S)-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: (R,S)-, (S,R)-, and (S,S)-. Thus, the ET efficiency is identical for (S,R)- and (R,S)-enantiomers, while RET differs by 1.6 times. For (S,S)-, the CIDNP coefficient is almost an order of magnitude greater than for (R,S)- and (S,R)-. To understand the source of this difference, hyperpolarization of (S,S)-and (R,S)- has been calculated using theory involving the electron dipole–dipole interaction in the secular equation.     

Lipids and Fatty Acids of the Gonads of Sea Urchin Diadema setosum (Echinodermata) From the Coastal Area of the Nha Trang Bay,Central Vietnam

The sea urchin Diadema setosum is edible and desirable as food by locals in central Vietnam and a promising target for potential fishing. The lipid profiles of the gonads of the sea urchin inhabiting the coastal area in Nha Trang Bay are studied for the first time. The determination of the content of the total lipids (TL), total phospholipids (PL), monoacylglycerols (MAG), diacylglycerols (DAG), triacylglycerols (TAG), cholesterol (Chol), sterol esters, and free fatty acids (FFA) is analyzed by high-performance thin layer chromatography (HPTLC); the phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) are determined by high-pressure liquid chromatography (HPLC); and the fatty acid levels of TLs are identified using gas chromatography (GC). Non-polar TAG, FFA, Chol, and DAG dominated. The content of total PL is significant. PC is abundant among PL fractions, followed by PE, PI, and PS. The TLs contain a high proportion of PUFA, mainly due to arachidonic fatty acid and eicosapentanoic fatty acid. The (n−6)/(n−3) ratio is 1.68, and the atherogenic and thrombogenic indexes of D. setosum are 1.13 and 0.73. The results can be used in the development of marine bioprospecting and methodological approaches for the creation of functional substances.     

Modified track membranes with antibacterial properties

Microbiological contamination of polymeric membranes in the process of their exploitation is an essential problem of membrane technology. It results in the increase of manufacturing costs, destruction of membranes, operating life reduction and secondary contamination of water by the metabolism products of microorganisms. For the purpose of reduction of membrane biofouling and biodegradation investigation of adsorption of the guanidine containing oligomers on the surface of PET track membranes was conducted and their influence on the selectivity and antibacterial properties of the membranes was investigated. It was established that modified membranes have substantially higher resistance to biofouling.     

Isotactic and syndiotactic polypropylene/multi-wall carbon nanotube composites: synthesis and properties

Isotactic polypropylene (iPP) and syndiotactic polypropylene (sPP) nanocomposites containing 0.1–3.5 wt.% multi-wall carbon nanotubes (MWCNTs) have been synthesized via in situ polymerization method with the use of C₂- and C_s- symmetry zirconocenes activated by methylaluminoxane (MAO) in liquid propylene medium. Fracture morphology studies by SEM reveal different MWCNT dispersion efficiency in various polymer matrices, which arises from the catalytic peculiarities of the composite synthesis. Considerable Young’s modulus enhancement of iPP and sPP (25–66%) takes place even at low MWCNT loadings (below 0.5 wt.%). The obtained nanocomposites can find use as efficient electromagnetic shielding materials and microwave absorbing filters due to relatively low permittivity values and considerable dielectric losses in microwave range. Calorimetry data demonstrate that MWCNTs exert evident influence as nucleating agents causing the rise of iPP and sPP crystallization temperature. Considerable retardation effect on iPP thermal oxidative degradation has been observed: the temperature of maximal weight loss rate rises by ~52 °C upon incorporating only 1.4 wt.% MWCNTs.     

Investigation on Purification of Saturated LiNO3 Solution Using Titanium Phosphate Ion Exchanger: Kinetics Study

Lithium compounds are of high interest to many industries. The presence of undesirable impurities in Li precursors leads to uncontrolled change in the functional properties of final compounds. Therefore, the development of reliable methods for lithium salt purification is considered a key factor for their application in various industries. This work focuses on the application of a titanium phosphate ion exchanger (Li-TiOP) toward Cu²⁺, Co²⁺, Mn²⁺, Ni²⁺, and Cr³⁺ ions in the purification of a saturated LiNO₃ solution. The sorption kinetics of the selected ions, considering external and internal mass transfer, as well as chemical interaction, were deeply studied. The kinetic study showed that the values of intraparticle diffusion rate and effective diffusion coefficients for the studied ions decreased in the following order: Cr(III) ˃ Cu(II) Mn(II) ˃ Co(II) ˃ Ni(II). For all the selected ions, chemical interaction was described with a pseudo-second-order reaction model. The sorption kinetics were controlled by the size of the solvated metal ion, its effective charge, the electronic structure of the adsorbed ion, and the interaction with the functional groups of the sorbent. Due to fast kinetics, the high degree of removal of trace quantities of the impurities this material gives it consideration as a promising sorbent for the deep purification of lithium salts.