PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

α7-Type nicotinic acetylcholine receptor (α7-nAChR) promotes the growth and metastasis of solid tumors. Secreted Ly6/uPAR-Related Protein 1 (SLURP-1) is a specific negative modulator of α7-nAChR produced by epithelial cells. Here, we investigated mechanisms of antiproliferative activity of recombinant SLURP-1 in epidermoid carcinoma A431 cells and activity of SLURP-1 and synthetic 21 a.a. peptide mimicking its loop I (Oncotag) in a xenograft mice model of epidermoid carcinoma. SLURP-1 inhibited the mitogenic pathways and transcription factors in A431 cells, and its antiproliferative activity depended on α7-nAChR. Intravenous treatment of mice with SLURP-1 or Oncotag for 10 days suppressed the tumor growth and metastasis and induced sustained changes in gene and microRNA expression in the tumors. Both SLURP-1 and Oncotag demonstrated no acute toxicity. Surprisingly, Oncotag led to a longer suppression of pro-oncogenic signaling and downregulated expression of pro-oncogenic miR-221 and upregulated expression of KLF4 protein responsible for control of cell differentiation. Affinity purification revealed SLURP-1 interactions with both α7-nAChR and EGFR and selective Oncotag interaction with α7-nAChR. Thus, the selective inhibition of α7-nAChRs by drugs based on Oncotag may be a promising strategy for cancer therapy.

Purpose to study the tumor-forming activity of wild-type MC F-7 cells carrying a full set of porins (VDAC 1, VDAC 2, VDAC 3), as well as their genetically modified cells, from which one of the isoforms was removed (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO, MC F -7 VDAC 3 KO).Material and Methods. The study was aimed at establishing of an animal model of orthotopic tumors in the mammary gland of immunodeficient BAL B/c nude mice by implanting a suspension of human breast cancer cells (MC F-7) and derivatives of these cells generated by targeted knockout of one of the selected mitochondrial porin isoforms (VDAC 1, VDAC 2 or VDAC 3). Suspensions of either wild-type MC F-7 cell lines containing all three porin isoforms (VDAC 1, VDAC 2 and VDAC 3) or their VDAC -deficient derivatives (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO) were injected into mammary fat pads of BAL B/c nude mice at a dose of 4x106 cells per injection. A pathomorphological analysis of the place of implantation of tumor cells, the tumor itself, as well as the organs of the abdominal and thoracic cavity was carried out.Results. The study shows the feasibility of successful creation of orthotopic tumors in the adipose tissue of immunodeficient BAL B/c nude mice with MC F-7 human breast cancer epithelial cells containing a complete set of mitochondrial porin isoforms and their VDAC -deficient derivatives. The tumor-forming activity of the implanted cells was shown to correlate with their cytotoxic effect on the internal organs of animals. Pathological analysis showed that all implanted cell cultures, such as MC F-7 WT, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO, except for MC F-7 VDAC 1 KO cells, which did not form tumors, caused pathological changes in the lungs, liver and spleen, as well as the presence of other tumor-like lesions.Conclusion. The data obtained will be used to optimize the injection volume and cell number, as well as to refine the dynamics of tumor growth, suitable for studying the effect of anticancer drugs on tumors formed by human breast cancer cells (MC F-7) and its genetically modified VDAC -deficient derivatives.

Представлены результаты исследования активности нового полипептидного модулятора TRPV1-рецепторов — АРНС2, выделенного из анемоны Heteractis crispa. Показано, что АРНС2 обладает анальгетическими свойствами, не нарушает нормальной двигательной активности и не изменяет температуру тела и гемостаз экспериментальных животных, что имеет большую практическую ценность для создания эффективных анальгетиков нового поколения. В исследовании гемодинамической активности наблюдается краткосрочное повышение ЧСС. Дальнейшее исследование особенностей связывания этого полипептида с рецептором TRPV1 может открыть подходы к созданию других антагонистов этого рецептора.

The activity of APHC2, a new polypeptide modulator of TRPV1 receptors that was isolated from Heteractis crispa, is studied. It was established that APHC2 possessed analgesic properties, did not disturb normal locomotor activity, and did not change body temperature and hemostasis of experimental animals. These attributes could be of great practical value for designing a new generation of efficacious analgesics. A brief increase of heart rate was observed during studies of the hemodynamic activity. Further investigation of the binding specifics of this polypeptide with TRPV1 receptors could open approaches to discovering other antagonists of these receptors.

Показано, что полипептидные анальгетические соединения APCH3 (ингибитор TRPV1 рецептора) и РТ1 (ингибитор P2X3 рецептора) не оказывают действия на сердечно-сосудистую и дыхательную системы как при однократном, так и при многократном введении мышам. Низкомолекулярное вещество севанол (ингибитор ASIC3 рецепторов) не влияет на сердечно-сосудистой систему, однако при длительном применении в течение 14 дней влияет на параметры дыхательной системы, достоверно увеличивая частоту дыхания и максимальный поток выдоха.

The polypeptide analgesic compounds APCH3 (a TRPV1 receptor inhibitor) and PT1 (a P2X3 receptor inhibitor) were shown not to act on the cardiovascular system or respiratory system when given either as single or multiple doses in mice. The low molecular weight compound sevanol (an ASIC3 receptor inhibitor) had no effect on the cardiovascular system, but prolonged use for 14 days affected measures of the respiratory system, significantly increasing respiratory rate and peak expiratory flow rate.

Preclinical studies on systemic toxicity and allergenic properties of amide form of HLDF-6 peptide in order to study the safety of its use as a drug with nootropic activity when administered intranasally were conducted. Studies were performed on male and female SD (Sprague Dawley) rats and CD-1 mice. Test results have demonstrated a lack of toxic effects of the study drug at the doses used in this rote of administration.

Morphometric characters of laboratory animals measured in different laboratories by different investigators are varied essentially. Apparently, this difference is caused by various influences of environment, depends on the way, moment and a place of blood sampling, dietary, animal age and some other factors. Standard conditions of animal’s maintenance are necessary for valid and reproducible research data therefore much attention now is given to the experimental animals care and use. This paper summarizes morphometric characters of SD (Sprague Dawley) rats mice which had SPF status (specific pathogen free) and were housed in standard conditions recommended for laboratory rodents maintenance.