I. A. Shchepetkin

Bio: I. A. Shchepetkin is an academic researcher from Tomsk Polytechnic University. The author has contributed to research in topics: Brain positron emission tomography & Molecular imaging. The author has an hindex of 1, co-authored 2 publications receiving 3 citations. Previous affiliations of I. A. Shchepetkin include Montana State University.

c-Jun N-Terminal Kinases and Their Pharmacological Modulation in Ischemic and Reperfusion Brain Injury

Abstract: We present here a review of the literature on the role of c-Jun N-terminal kinases (JNK) and their inhibitors in ischemic and reperfusion brain injuries. The functions of JNK in the signal mechanisms involved in brain damage in ischemia and reperfusion are discussed. Effects linked with inhibition of JNK with synthetic and natural compounds in experimental models of ischemia and reperfusion brain injury are described. Results from experimental studies show that JNK provide potential therapeutic targets for protecting the brain from ischemic stroke. However, the fact that JNK have numerous physiological functions prevents systematic use of nonspecific inhibitors of these kinases for therapeutic purposes. The authors conclude that this task requires a further search for selective JNK3 inhibitors.

Novel targets for positron emission tomography (PET) radiopharmaceutical tracers for visualization of neuroinflammation

Abstract: Non-invasive molecular imaging techniques can enhance diagnosis of neurological diseases to achieve their successful treatment. Positron emission tomography (PET) imaging can identify activated microglia and provide detailed functional information based on molecular biology. This imaging modality is based on detection of isotope labeled tracers, which emit positrons. The review summarizes the developments of various radiolabeled ligands for PET imaging of neuroinflammation.

Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins.

Abstract: Axonal degeneration and neuronal cell death are fundamental processes in development and contribute to the pathology of neurological disease in adults. Both processes are regulated by BCL-2 family proteins which orchestrate the permeabilization of the mitochondrial outer membrane (MOM). MOM permeabilization (MOMP) results in the activation of pro-apoptotic molecules that commit neurons to either die or degenerate. With the success of small-molecule inhibitors targeting anti-apoptotic BCL-2 proteins for the treatment of lymphoma, we can now envision the use of inhibitors of apoptosis with exquisite selectivity for BCL-2 family protein regulation of neuronal apoptosis in the treatment of nervous system disease. Critical to this development is deciphering which subset of proteins is required for neuronal apoptosis and axon degeneration, and how these two different outcomes are separately regulated. Moreover, noncanonical BCL-2 family protein functions unrelated to the regulation of MOMP, including impacting necroptosis and other modes of cell death may reveal additional potential targets and/or confounders. This review highlights our current understanding of BCL-2 family mediated neuronal cell death and axon degeneration, while identifying future research questions to be resolved to enable regulating neuronal survival pharmacologically.

Research on system response matrix modelling method of rectangular PET scanner based on Monte Carlo simulation

Abstract: In positron emission tomography (PET) image reconstruction, the accurate system response matrix (SRM) is one of the key factors for reconstructing high-quality images. To reduce the influence of various factors on the spatial resolution, this paper focuses on calculating the SRM based on Monte Carlo (MC) simulation and proposes a method based on system geometric symmetry to reduce the simulation time. We split the symmetry into two types: intra-ring symmetry and inter-axis symmetry, a total of 208 times the symmetry is used. According to the standards formulated by the American National Electrical Manufacturers Association (NEMA), the spatial resolution and image quality are assessed by simulation experiments. Results of point source measurement show that the full width at half maximum (FWHM) range in each direction is about 1.1–1.3 mm, the average value is about 1.2 mm. In Derenzo phantom imaging, the MC method can clearly distinguish the 1.2 mm rods. To assess image quality, we calculated the uniformity of the image, contrast recovery coefficients (CRC), and coefficient of variation (COV). At the same time, we compared with the ray tracing (RT) and pixel drive (PD) models. In general, the MC method achieves better results in simulation experiments than RT and PD methods.

Experimental and Computational Investigation of the Oxime Bond Stereochemistry in c-Jun N-terminal Kinase 3 Inhibitors 11H-Indeno[1,2-b]quinoxalin-11-one Oxime and Tryptanthrin-6-oxime

Abstract: 11H-Indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and tryptanthrin-6-oxime are potent c-Jun N-terminal kinase 3 (JNK-3) inhibitors demonstrating neuroprotective, anti-inflammatory and anti-arthritic activity. However, the stereochemical configuration of the oxime carbon–nitrogen double bond (E- or Z-) in these compounds was so far unknown. In this contribution, we report the results of the determination of the double bond configuration in the solid state by single crystal X-ray diffraction and in solution by 1D and 2D NMR techniques and DFT calculations. It was found that both in the solid state and in solution, IQ-1 adopts the E-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed Z-configuration that could be stabilized only by an intramolecular hydrogen bond.