The analysis of structure-anticancer and antiviral activity relationships for macrocyclic pyridinophanes and their analogues on the basis of 4D QSAR models (simplex representation of molecular structure)

A new 4D-QSAR approach has been considered. For all investigated molecules the 3D structural models have been created and the set of conformers (fourth dimension) have been used. Each conformer is represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). The investigation of influence of molecular structure of macrocyclic pyridinophanes, their analogues and certain other compounds on anticancer and antiviral (anti-influenza, antiherpes and antiadenovirus) activity has been carried out by means of the 4D-QSAR. Statistic characteristics for QSAR of PLS (partial least squares) models are satisfactory (R = 0.92-0.97; CVR = 0.63-0.83). Molecular fragments increasing and decreasing biological activity were defined. This information may be useful for design, and direct synthesis of novel anticancer and antiviral agents.     

Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy

Biochemistry (Moscow) - Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world...     

Peculiarities of Alteromonas macleodii strains reflects their deep/surface habitation rather than geographical distribution

The phenotypic, chemotaxonomic and genetic peculiarities of 5 deep strains of Alteromonas macleodii (isolated from Adriatic and Ionian Sea water from a depth of 1,000-3,500 m) and 5 strains of the same species isolated from the surface layer of Aegean, Andaman, Black Sea and Atlantic Ocean water near the British shore have been studied. Electron microscopy has shown that the deep strains' cells were, on average, two times longer (2.1±0.2×0.7±0.1 μm) than the surface strains' (1.1±0.1×0.6±0.1 μm). Using fatty acid analysis (particularly the mono-unsaturated C16:1 and C18:1 fatty acids contents) the deep and surface isolates were clearly separated into two clusters. Distinctions between them were also found in different lectin binding capacity, which is probably determined by the structure of their extracellular polysaccharide matrix. Analysis of the results of PCR with primers to repeated nucleotide sequences revealed a higher level of genetic polymorphism in surface strains in comparison with the deep isolates. This division was confirmed by the cluster analysis method though it was not as clear as in the fatty acids analysis. The described peculiarities are probably reflective of specific conditions in which A. macleodii strains live on the surface or in the depth of the world's oceans.     

Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood

Point mutations in the α-synuclein coding gene may lead to the development of Parkinson's disease (PD). PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as SNCA and A30T, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation A53T is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by α-synuclein accumulation. The affective and alcohol-drinking phenotypes remained unaltered in female PDGF-hA53T-synuclein-transgenic (A53T) mice during both early and late adulthood. Brain region-specific activation of ceramide-producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the A53T mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety- and depression-like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the A53T gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.

     

Effect of 1,3;1,6-β-D-glucan on Infection of Detached Tobacco Leaves with Tobacco Mosaic Virus

Glucan preparations were obtained by transformation of laminaran from the alga Laminaria cichorioides with endo-β-1,3-glucanase from marine mollusks. These preparations, like those of other sources, have an inhibitory effect on tobacco mosaic virus (TMV) infection of detached leaves of local and systemic host tobacco plants.