[Hostility as a manifestation of attachment disorders in depression].

Objective: To analyze the relationship between hostility and attachment disorders in endogenous depression.

Material And Methods: The study included 49 patients with a diagnosis of depressive disorder, all of them completed the Simptom Check List-90-Revised (SCL-90R); the Buss-Perry Aggression Questionnaire; the Experiences in Close Relationships-Revised (ECR-R); Ich-Struktur-Test nach Ammon. The patients were assessed using the Hamilton Depression Rating Scale (HDRS-17).

Feasibility of Co-Targeting HER3 and EpCAM Using Seribantumab and DARPin-Toxin Fusion in a Pancreatic Cancer Xenograft Model.

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets.

A Low-Molecular-Weight BDNF Mimetic, Dipeptide GSB-214, Prevents Memory Impairment in Rat Models of Alzheimer's Disease.

Brain-derived neurotrophic factor (BDNF) is known to be involved in the pathogenesis of Alzheimer's disease (AD). However, the pharmacological use of full-length neurotrophin is limited, because of its macromolecular protein nature. A dimeric dipeptide mimetic of the BDNF loop 1, bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylene diamide (GSB-214), was designed at the Zakusov Research Institute of Pharmacology.

Experimental HER2-Targeted Therapy Using ADAPT6-ABD-mcDM1 in Mice Bearing SKOV3 Ovarian Cancer Xenografts: Efficacy and Selection of Companion Imaging Counterpart.

Overexpression of the human epidermal growth factor receptor 2 (HER2) in breast and gastric cancer is exploited for targeted therapy using monoclonal antibodies and antibody-drug conjugates. Small engineered scaffold proteins, such as the albumin binding domain (ABD) derived affinity proteins (ADAPTs), are a promising new format of targeting probes for development of drug conjugates with well-defined structure and tunable pharmacokinetics. Radiolabeled ADAPT6 has shown excellent tumor-targeting properties in clinical trials.

The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy.

Human epidermal growth factor receptor 2 (HER2) is a clinically validated target for breast cancer therapy. Previously, a drug-fused HER2-targeting affinity protein construct successfully extended the survival of mice bearing HER2-expressing xenografts. The aim of this study was to evaluate the influence of the number and positioning of the protein domains in the drug conjugate.

Affibody-Mediated PNA-Based Pretargeted Cotreatment Improves Survival of Trastuzumab-Treated Mice Bearing HER2-Expressing Xenografts.

Treatment of patients with human epidermal growth factor receptor 2 (HER2)-expressing tumors using the monoclonal antibody trastuzumab increases survival. The Affibody-based peptide nucleic acid (PNA)-mediated pretargeted radionuclide therapy has demonstrated efficacy against HER2-expressing xenografts in mice. Structural studies suggest that Affibody molecules and trastuzumab bind to different epitopes on HER2.

[Dynamics of psychopathological symptoms during the COVID-19 pandemic in Russia].

Objective: The results of the analysis of psychopathological symptom dynamics during the COVID-19 pandemic in Russia are presented.

Material And Methods: The study uses the data of the Internet survey, which included a block of sociodemographic questions and the SCL-90-R symptomatic questionnaire. Nine hundred and eight responses received from 22.

Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model.

Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment.

Radionuclide therapy using ABD-fused ADAPT scaffold protein: Proof of Principle.

Molecular recognition in targeted therapeutics is typically based on immunoglobulins. Development of engineered scaffold proteins (ESPs) has provided additional opportunities for the development of targeted therapies. ESPs offer inexpensive production in prokaryotic hosts, high stability and convenient approaches to modify their biodistribution.

Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1.

Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies.

The Anxiolytic Effect of the Neuropeptide Cycloprolylglycine Is Mediated by AMPA and TrkB Receptors.

Previously we have shown that the neuropeptide cycloprolylglycine is an endogenous positive modulator of AMPA receptors and assumed that the pharmacological effects of CPG are associated with the brain neurotrophic factor. In this paper, we have first demonstrated that DNQX, an inhibitor of AMPA receptors, and K252A, an ihibitor of Trk receptors, prevented the anxiolytic effect of CPG, which confirms the formulated hypothesis.

Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model.

Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis.

Vesicle Clustering in a Living Synapse Depends on a Synapsin Region that Mediates Phase Separation.

Liquid-liquid phase separation is an increasingly recognized mechanism for compartmentalization in cells. Recent in vitro studies suggest that this organizational principle may apply to synaptic vesicle clusters. Here we test this possibility by performing microinjections at the living lamprey giant reticulospinal synapse.

[Socio-medical and constitutional aspects of longevity in Pridnestrovie (Transnistria).].

A comprehensive study of socio-medical and constitutional aspects of longevity in Pridnestrovie (Transnistria) was carried out. The level of longevity, the frequency of occurrence of hereditary predisposition to longevity, the features of anthropometric indicators, the somatic and psychological constitution of long-livers, their state of health, degree of ability to self-service, marital status, professional activity and level of physical activity throughout life are revealed.

An Endocytic Scaffolding Protein together with Synapsin Regulates Synaptic Vesicle Clustering in the Drosophila Neuromuscular Junction.

Unlabelled: Many endocytic proteins accumulate in the reserve pool of synaptic vesicles (SVs) in synapses and relocalize to the endocytic periactive zone during neurotransmitter release. Currently little is known about their functions outside the periactive zone. Here we show that in the Drosophila neuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocalizes during the SV cycle and forms a functional complex with the SV-associated phosphoprotein synapsin, previously implicated in SV clustering.

Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between endophilin and intersectin at synapses.

Neurotransmission involves the exo-endocytic cycling of synaptic vesicle (SV) membranes. Endocytic membrane retrieval and clathrin-mediated SV reformation require curvature-sensing and membrane-bending BAR domain proteins such as endophilin A. While their ability to sense and stabilize curved membranes facilitates membrane recruitment of BAR domain proteins, the precise mechanisms by which they are targeted to specific sites of SV recycling has remained unclear.

[Specifics of emotional biases in decision making in juvenile endogenous attack-like schizophrenia].

Objective: To identify the ability of schizophrenic patients to make decisions based on the mechanism of emotional learning (Damasio's somatic markers hypothesis).

Material And Methods: Forty patients with the juvenile endogenous attack-like schizophrenia were investigated. Based on the clinical data, the patients were separated into three groups with different levels of negative symptoms.

Linear antimicrobial peptides from Ectatomma quadridens ant venom.

Venoms from three poneromorph ant species (Paraponera clavata, Ectatomma quadridens and Ectatomma tuberculatum) were investigated for the growth inhibition of Gram-positive and Gram-negative bacteria. It was shown that the venom of E. quadridens and its peptide fraction in particular possess marked antibacterial action.

Interaction of linear cationic peptides with phospholipid membranes and polymers of sialic acid.

Polysialic acid (PSA) is a natural anionic polymer typically occurring on the outer surface of cell membranes. PSA is involved in cell signaling and intermolecular interactions with proteins and peptides. The antimicrobial potential of peptides is usually evaluated in model membranes consisting of lipid bilayers but devoid of either PSA or its analogs.

Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer's Disease.

Dipeptide mimetic of the nerve growth factor (NGF) loop 4, hexamethylenediamide bis-(N-monosuccinyl- glutamyl-lysine) (GK-2), was synthesized at the V.V. Zakusov Scientific Research Institute of Pharmacology of the Russian Academy of Medical Sciences.

The dynamin-binding domains of Dap160/intersectin affect bulk membrane retrieval in synapses.

Dynamin-associated protein 160 kDa (Dap160)/intersectin interacts with several synaptic proteins and affects endocytosis and synapse development. The functional role of the different protein interaction domains is not well understood. Here we show that Drosophila Dap160 lacking the dynamin-binding SH3 domains does not affect the development of the neuromuscular junction but plays a key role in synaptic vesicle recycling.

[Neuroprotective effects of a dipeptide mimetic on the GK-2 nerve growth factor in model of permanent common carotid artery occlusion in rats].

The behavioral and biochemical effects of a new dipeptide mimetic of the GK-2 nerve growth factor (NGF) have been studied on a model of chronic cerebral ischemia induced by permanent common carotid artery occlusion in rats. It is established that subchronic intraperitoneal injections of GK-2 (0.5 mg/kg) 4 h after surgery, followed by seven more injections made every 24 h, fully prevent the death of operated animals and reduces the development of habitation deficit (open-field test) and decrease in exploratory activity (novel object examination) two weeks after surgery, as well as fully restores the viability of cerebral cortex cells and decreases the hyperexpression of HSP70 in cerebral cortex.

Mechanism underlying the protective effect of glycine in energetic disturbances in brain tissues under hypoxic conditions.

Glycine stabilizes energetics of brain mitochondria under conditions of brain hypoxia in vivo modeled by ligation of the common carotid artery in rats. Hypoxia reduced respiratory control in brain cortex mitochondria from 7.7 ± 0.

Antiparkinsonian properties of a nerve growth factor dipeptide mimetic GK-2 in in vivo experiments.

An intraperitoneal injection of GK-2 (dipeptide mimetic of nerve growth factor, 0.01-5.00 mg/kg) 24 h before the adverse exposure reduced the severity of haloperidol-induced catalepsy in rats.

An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling.

Clathrin-mediated vesicle recycling in synapses is maintained by a unique set of endocytic proteins and interactions. We show that endophilin localizes in the vesicle pool at rest and in spirals at the necks of clathrin-coated pits (CCPs) during activity in lamprey synapses. Endophilin and dynamin colocalize at the base of the clathrin coat.