Combined use of laser Doppler flowmetry and skin thermometry for functional diagnostics of intradermal finger vessels

We introduce a noninvasive diagnostic approach for functional monitoring of blood microflows in capillaries and thermoregulatory vessels within the skin. The measuring system is based on the combined use of laser Doppler flowmetry and skin contact thermometry. The obtained results suggest that monitoring of blood microcirculation during the occlusion, performed in conjunction with the skin temperature measurements in the thermally stabilized medium, has a great potential for quantitative assessment of angiospatic dysfunctions of the peripheral blood vessels. The indices of blood flow reserve and temperature response were measured and used as the primarily parameters of the functional diagnostics of the peripheral vessels of skin. Utilizing these parameters, a simple phenomenological model has been suggested to identify patients with angiospastic violations in the vascular system

Neuroblastoma Origin and Therapeutic Targets for Immunotherapy

Neuroblastoma is a pediatric solid cancer of heterogeneous clinical behavior. The unique features of this type of cancer frequently hamper the process of determining clinical presentation and predicting therapy effectiveness. The tumor can spontaneously regress without treatment or actively develop and give rise to metastases despite aggressive multimodal therapy. In recent years, immunotherapy has become one of the most promising approaches to the treatment of neuroblastoma. Still, only one drug for targeted immunotherapy of neuroblastoma, chimeric monoclonal GD2-specific antibodies, is used in the clinic today, and its application has significant limitations. In this regard, the development of effective and safe GD2-targeted immunotherapies and analysis of other potential molecular targets for the treatment of neuroblastoma represents an important and topical task. The review summarizes biological characteristics of the origin and development of neuroblastoma and outlines molecular markers of neuroblastoma and modern immunotherapy approaches directed towards these markers

Combined use of laser Doppler flowmetry and skin thermometry for functional diagnostics of intradermal finger vessels

We introduce a noninvasive diagnostic approach for functional monitoring of blood microflows in capillaries and thermoregulatory vessels within the skin. The measuring system is based on the combined use of laser Doppler flowmetry and skin contact thermometry. The obtained results suggest that monitoring of blood microcirculation during the occlusion, performed in conjunction with the skin temperature measurements in the thermally stabilized medium, has a great potential for quantitative assessment of angiospatic dysfunctions of the peripheral blood vessels. The indices of blood flow reserve and temperature response were measured and used as the primarily parameters of the functional diagnostics of the peripheral vessels of skin. Utilizing these parameters, a simple phenomenological model has been suggested to identify patients with angiospastic violations in the vascular system

Combined use of laser Doppler flowmetry and skin thermometry for functional diagnostics of intradermal finger vessels

Abstract We introduce a noninvasive diagnostic approach for functional monitoring of blood microflows in capillaries and thermoregulatory vessels within the skin. The measuring system is based on the combined use of laser Doppler flowmetry and skin contact thermometry. The obtained results suggest that monitoring of blood microcirculation during the occlusion, performed in conjunction with the skin temperature measurements in the thermally stabilized medium, has a great potential for quantitative assessment of angiospatic dysfunctions of the peripheral blood vessels. The indices of blood flow reserve and temperature response were measured and used as the primarily parameters of the functional diagnostics of the peripheral vessels of skin. Utilizing these parameters, a simple phenomenological model has been suggested to identify patients with angiospastic violations in the vascular system

PeptoGrid—Rescoring Function for AutoDock Vina to Identify New Bioactive Molecules from Short Peptide Libraries

Peptides are promising drug candidates due to high specificity and standout safety. Identification of bioactive peptides de novo using molecular docking is a widely used approach. However, current scoring functions are poorly optimized for peptide ligands. In this work, we present a novel algorithm PeptoGrid that rescores poses predicted by AutoDock Vina according to frequency information of ligand atoms with particular properties appearing at different positions in the target protein’s ligand binding site. We explored the relevance of PeptoGrid ranking with a virtual screening of peptide libraries using angiotensin-converting enzyme and GABAB receptor as targets. A reasonable agreement between the computational and experimental data suggests that PeptoGrid is suitable for discovering functional leads

Minibody-Based and scFv-Based Antibody Fragment-Drug Conjugates Selectively Eliminate GD2-Positive Tumor Cells

Ganglioside GD2 is a well-established target expressed on multiple solid tumors, many of which are characterized by low treatment efficiency. Antibody-drug conjugates (ADCs) have demonstrated marked success in a number of solid tumors, and GD2-directed drug conjugates may also hold strong therapeutic potential. In a recent study, we showed that ADCs based on the approved antibody dinutuximab and the drugs monomethyl auristatin E (MMAE) or F (MMAF) manifested potent and selective cytotoxicity in a panel of tumor cell lines and strongly inhibited solid tumor growth in GD2-positive mouse cancer models. Here, we employed two different GD2-binding moieties–minibodies and scFv fragments that carry variable antibody domains identical to those of dinutuximab, and site-directly conjugated them to MMAE or MMAF by thiol-maleimide chemistry with drug-to-antibody ratios (DAR) of 2 and 1, respectively. Specific binding of the antibody fragment-drug conjugates (FDCs) to GD2 was confirmed in direct ELISA, flow cytometry, and confocal microscopy. Selective cytotoxic and cytostatic effects of the conjugates were observed in GD2-positive but not GD2-negative neuroblastoma and melanoma cell lines. Minibody-based FDCs demonstrated more pronounced cytotoxic effects and stronger antigen binding compared to scFv-based FDCs. The developed molecules may offer considerable practical benefit, since antibody fragment-drug conjugates are capable of enhancing therapeutic efficacy of ADCs by improving their pharmacokinetic characteristics and reducing side effects

Data_Sheet_1_The novel peptide LCGM-10 attenuates metabotropic glutamate receptor 5 activity and demonstrates behavioral effects in animal models.docx

We employed a structural bioinformatics approach to develop novel peptides with predicted affinity to the binding site for negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5). Primary screening in zebrafish (Danio rerio) revealed a stimulatory effect of two peptides, LCGM-10 and LCGM-15. Target validation studies using calcium ion flux imaging and a luciferase reporter assay confirmed mGluR5 as the target. LCGM-10 showed greater potency than LCGM-15; it was comparable to that of the mGluR5 NAM 2-methyl-6-(phenylethynyl) pyridine (MPEP). Rodent behavioral screening in the open field and elevated plus maze revealed increased locomotor activity in both tests after acute LCGM-10 treatment, supported by further analysis of home cage spontaneous locomotor activity (SLA). The stimulating effect of a single LCGM-10 administration on SLA was evident up to 60 min after administration and was not accompanied by hypokinetic rebound observed for caffeine. According to our results, LCGM-10 has therapeutic potential to treat hypo- and dyskinesias of various etiologies. Further investigation of LCGM-10 effects in the delay discounting model of impulsive choice in rats revealed reduced trait impulsivity after single and chronic administrations, suggesting potential implication for attention deficit hyperactivity disorder, obsessive compulsive disorder, and addictions.</p