Репозиторий Университета

Constituting one of Earth’s major biomes, steppes are characterised by naturally treeless extra-tropical vegetation. The formation of the Eurasian steppe belt, the largest steppe region in the world, began in Central Asia during the Neogene. In the glacial stages of the Pleistocene, steppe displaced forest vegetation, which in turn recolonised the area during the warmer interglacial periods, thus affecting the distribution of plants adapted to these habitats. Krascheninnikovia ceratoides (Chenopodiaceae) is a plant characteristic of dry steppe and semi-desert formations. Earlier studies showed that the ancestor of this autochthonous steppe element originated in Central Asia during the Miocene/Pliocene, i.e., in the same region and at the same time as the first appearance of steppe vegetation. However, as the extant lineages of Krascheninnikovia ceratoides diversified only 2.2 ± 0.9 Mya, it may represent a modern element of current dry steppe and semi-desert formations, rather than a component of the first steppe precursors of the Miocene. As such, it may have capitalised on the climatic conditions of the cold stages of the Quaternary to expand its range and colonise suitable habitats outside of its area of origin. To test this hypothesis, phylogeographic methods were applied to high-resolution genotyping-by-sequencing data. Our results indicate that Krascheninnikovia originated in western Central Asia and the Russian Altai, then spread to Europe in the West, and reached North America in the East. The populations of eastern Central Asia and North America belong to the same clade and are genetically clearly distinct from the Euro-Siberian populations. Among the populations west of the Altai Mountains, the European populations are genetically distinct from all others, which could be the result of the separation of populations east and west of the Urals caused by the Pleistocene transgressions of the Caspian Sea.

Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.

Background: Although the relationship between acute alcohol consumption and injuries is well recognized, studies exploring how the time of day the drinking commences affects alcohol-related injuries have been scarce. This contribution examines the associations between the time at which the drinking began and the duration of the drinking, the volume of alcohol consumed, the injury type, and the blood alcohol concentration (BAC) level. Method: This study employed a cross-sectional survey, which was conducted in two hospital emergency departments (ED) in Chiangmai Province, Thailand. The sample was composed of 519 injured patients aged 18 years and older. Outcome measures included the BAC and type of injury. Exposures included the quantity of alcohol consumed, the time the drinking commenced, and the pattern of drinking involved. Results: The injured patients who drank alcohol within six hours prior to sustaining their injury were more likely to get injured and present themselves at the ED at night (20:00–04:00) compared to those who sustained an injury but did not drink in the hours prior. However, this relationship was only true for unintentional injuries, not intentional ones. The majority of participants consumed their first drink between 16:00 and 20:00. On average, among the 104 patients who drank prior to sustaining an injury, the total amount of alcohol consumed was 6.9 drinks, the duration of drinking was 2.6 h, the rate of drinking was 6.0 drinks/hour, and the BAC was 0.119 gm%. Every drink increased the BAC by 0.012 gm% and each year of increasing age increased the BAC by 0.003 gm%. People who were older, less educated, and drank more frequently tended to have their first drink earlier than other drinkers. An earlier start to their drinking resulted in a faster pace of drinking and a higher BAC. Conclusions: BAC increased with the total amount of alcohol consumed and the age of the drinker. Different groups of people had their first drink at different times of the day, resulting in differences in the rate of drinking, the BAC, the time of injury, and the time they presented to the ED after injury.

The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions. [MediaObject not available: see fulltext.]

The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2  mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2  mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection. (G2019S) (G2019S)

Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression. Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October 30 th, 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random-effects empirical Bayes model. Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of -8.94 points (CI [-10.04,-7.84], p < 0.01) in the BDI scale, of -5.90 points (CI [-9.92,-1.88], p < 0.01) in the BDI-II scale and of -6.19 points (CI [-9.52,-2.86], p < 0.01) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of -4.10 (CI [-7.31,-0.89], p = 0.01) points in the HIT6 scale, -32.05 (CI [-55.96,-8.14], p = 0.01) in the MIDAS scale, -1.7 (CI [-3.27,-0.13], p = 0.03) points in the VAS scale and of -6.27 (CI [-8.48,-4.07], p < 0.01) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores. Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.

DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of “deterministic” CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of “stochastic” CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.

DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of “deterministic” CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of “stochastic” CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.

DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of “deterministic” CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of “stochastic” CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe ), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe ). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca ] ) in astrocytes. Administration of Fe  or Fe  in μM concentrations evoked [Ca ]  in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca ]  through two distinct molecular cascades. Uptake of Fe  by DMT1 inhibits astroglial Na -K -ATPase, which leads to elevation in cytoplasmic Na  concentration, thus reversing Na /Ca  exchanger and thereby generating Ca  influx. Uptake of Fe  by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP ), thus triggering InsP  receptor-mediated Ca  release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload. 2+ 3+ 2+ 2+ 3+ 2+ 2+ 2+ + + + + 2+ 2+ 3+ 2+ i i i 3 3

Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe ), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe ). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca ] ) in astrocytes. Administration of Fe  or Fe  in μM concentrations evoked [Ca ]  in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca ]  through two distinct molecular cascades. Uptake of Fe  by DMT1 inhibits astroglial Na -K -ATPase, which leads to elevation in cytoplasmic Na  concentration, thus reversing Na /Ca  exchanger and thereby generating Ca  influx. Uptake of Fe  by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP ), thus triggering InsP  receptor-mediated Ca  release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload. 2+ 3+ 2+ 2+ 3+ 2+ 2+ 2+ + + + + 2+ 2+ 3+ 2+ i i i 3 3

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

The current consensus on prevention of re-establishment of malaria is based on the following principles: (1) Fundamental role of general health services; (2) Surveillance; (3) Vector control; (4) Border actions; (5) Intersectoral collaboration. These principles are critically reviewed, and it is pointed out that alertness of the general health services to suspected malaria (vigilance) needs to be maintained everywhere, while health education is rational only if targeting high-risk sub-populations. It is argued that prevention of re-establishment of malaria transmission should be integrated with prevention of malaria mortality in cases of imported malaria, and that this requires collaboration with entities dealing with travellers’ health and the availability of chemoprophylaxis and other measures for travellers to malaria endemic countries.