Phosphodiesterase 8 (PDE8) regulates chemotaxis of activated lymphocytes

The immune system depends on chemokines to recruit lymphocytes to tissues in inflammatory diseases. This study identifies PDE8 as a new target for inhibition of chemotaxis of activated lymphocytes. Chemotactic responses of unstimulated and concanavalin A-stimulated mouse splenocytes and their modulation by agents that stimulate the cAMP signaling pathway were compared. Dibutyryl cAMP inhibited migration of both cell types. In contrast, forskolin and 3-isobutyl-1-methylxanthine each inhibited migration of unstimulated splenocytes, with little effect on migration of stimulated splenocytes. Only dipyridamole alone, a PDE inhibitor capable of inhibiting PDE8, strongly inhibited migration of stimulated and unstimulated splenocytes and this inhibition was enhanced by forskolin and reversed by a PKA antagonist. Following concanavalin A stimulation, mRNA for PDE8A1 was induced. These results suggest that in employing PDE inhibitor therapy for inflammatory illnesses, inhibition of PDE8 may be required to inhibit migration of activated lymphocytes to achieve a full therapeutic effect.     

Discovery of potent carbonic anhydrase,acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine‐4‐ones synthesized on an acetophenone base

Compounds containing nitrogen and sulfur atoms can be widely used in various fields, including industry, medicine, biotechnology, and chemical technology. Among them, amides of acids and heterocyclic compounds have an important place. These amides and thiazolidine‐4‐ones showed good inhibitory action against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoforms. AChE exists at high concentrations in the brain and red blood cells. BChE is an important enzyme that is plentiful in the liver, and it is released into the blood in a soluble form. They were demonstrated to have effective inhibition profiles with K_i values of 23.76–102.75 nM against hCA I, 58.92–136.64 nM against hCA II, 1.40–12.86 nM against AChE, and 9.82–52.77 nM against BChE. On the other hand, acetazolamide showed K_i value of 482.63 ± 56.20 nM against hCA I, and 1019.60 ± 163.70 nM against hCA II. Additionally, Tacrine inhibited AChE and BChE, showing K_i values of 397.03 ± 31.66 and 210.21 ± 15.98 nM, respectively.     

Morphological features of shoots in <Emphasis Type="Italic">Plantago arenaria</Emphasis> Waldst. et Kit. (Plantaginaceae L.) under different ecological conditions

A comparative morphological analysis of P. arenaria herbarium specimens from different geographic locations has made it possible to describe the diversity of shoots and distinguish several ecomorphological types of plants. It has been shown that P. arenaria plants in overmoistened sites have a prostrate form with anisotropic shoots, rosetteless shoots shortened at the base are characteristic of plants growing on dense substrates, and rosette shoots are formed under conditions of moisture deficiency combined with high soil density or in plants growing on sandy slopes. Morphological plasticity of P. arenaria shoots provides for higher plant stability and survival.     

Novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes: Synthesis,characterization, acetylcholinesterase,butyrylcholinesterase, and carbonic anhydrase inhibitory properties

The thiolation reaction was carried out in a benzene solution at 80°C and p‐substituted ketones and mercaptoacetic acid in a molar ratio (1:4) of in the presence of a catalytic amount of toluene sulfonic acids. The enzyme inhibition activities of the novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives were investigated. These novel amides of 1,1‐bis‐(carboxymethylthio)‐1‐arylethanes derivatives showed good inhibitory action against acetylcholinesterase (AChE) butyrylcholinesterase (BChE), and human carbonic anhydrase I and II isoforms (hCA I and II). AChE inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. Many clinically established drugs are carbonic anhydrase inhibitors, and it is highly anticipated that many more will eventually find their way into the market. The novel synthesized compounds inhibited AChE and BChE with K_i values in the range of 0.64–1.47 nM and 9.11–48.12 nM, respectively. On the other hand, hCA I and II were effectively inhibited by these compounds, with K_i values between 63.27–132.34 and of 29.63–127.31 nM, respectively.     

Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL

Here, we provide evidence for a detrimental role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in neural death in T cell-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Clinical severity and neuronal apoptosis in brainstem motor areas were substantially reduced upon brain-specific blockade of TRAIL after induction of EAE through adoptive transfer of encephalitogenic T cells. Furthermore, TRAIL-deficient myelin-specific lymphocytes showed reduced encephalitogenicity when transferred to wild-type mice. Conversely, intracerebral delivery of TRAIL to animals with EAE increased clinical deficits, while naive mice were not susceptible to TRAIL. Using organotypic slice cultures as a model for living brain tissue, we found that neurons were susceptible to TRAIL-mediated injury induced by encephalitogenic T cells. Thus, in addition to its known immunoregulatory effects, the death ligand TRAIL contributes to neural damage in the inflamed brain.     

Cultivation of the gonococcus in nutrient broths

The dynamics of the multiplication of gonococci and the parameters of their growth have been studied in the process of batch cultivation in liquid culture media with different content of bovine blood serum. The protective and stimulating action of the serum on the growth of gonococci has been shown. The optimization of the process of cultivation has been carried out; as a result, the growth of test strains in a culture medium containing no serum has been achieved. Phasic changes in the ultrastructure of gonococci in the process of their cultivation in liquid media have been followed. 9- to 12-hour cultures of gonococci grown in liquid culture media have been found the most valuable and physiologically active.     

Immunomodulating therapy with myelopid in experimental Salmonella infection

The influence of myelopid on immunological characteristics in experimental Salmonella infection has been studied. This preparation has been found to produce a pronounced effect on the characteristics of immune response: it increases the number of T- and B-lymphocytes in the blood and the lymphoid organs. The indirect rosette-formation test has shown that myelopid facilitates earlier and more rapid binding and elimination of the antigen (S. typhimurium) from the body. Under the influence of myelopid the release of antigen-binding lymphocytes from the thymus to the peripheral lymphoid organs becomes more intensive.     

Biomorphology of <Emphasis Type="Italic">Actaea erythrocarpa</Emphasis> Fisch. individuals and ecological–demographic characterization of its cenopopulations

The ecotopes of Actaea erythrocarpa Fisch. cenopopulations are characterized according to five of Tsyganov’s scales using bioindication methods. The morphological polyvariation of vegetative organs appears as elongation of the A. erythrocarpa shoot metameric units under different ecological conditions. As has been shown, the biometric characteristics of A. erythrocarpa individuals depend on the ontogenetic state and habitat.     

Quantitative Analysis of Bacillus pumilus Serine Proteinases in Recombinant Bacillus Strains

Microbiology - A comparative study of the expression of B. pumilus extracellular serine proteinases (subtilisin-like proteinase and glutamyl endopeptidase) under the control of different promoters...