Effective antiprotease-antibiotic treatment of experimental anthrax

BACKGROUND: Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. In order to close a gap between our understanding of anthrax molecular pathology and the most prominent clinical features of the infectious process we undertook bioinformatic and experimental analyses of potential proteolytic virulence factors of B. anthracis distinct from lethal toxin. METHODS: Secreted proteins (other than lethal and edema toxins) produced by B. anthracis were tested for tissue-damaging activity and toxicity in mice. Chemical protease inhibitors and rabbit immune sera raised against B. anthracis proteases were used to treat mice challenged with B. anthracis (Sterne) spores. RESULTS: B. anthracis strain delta Ames (pXO1(-), pXO2(-)) producing no lethal and edema toxins secrets a number of metalloprotease virulence factors upon cultivation under aerobic conditions, including those with hemorrhagic, caseinolytic and collagenolytic activities, belonging to M4 and M9 thermolysin and bacterial collagenase families, respectively. These factors are directly toxic to DBA/2 mice upon intratracheal administration at 0.5 mg/kg and higher doses. Chemical protease inhibitors (phosphoramidon and 1, 10-phenanthroline), as well as immune sera against M4 and M9 proteases of B. anthracis, were used to treat mice challenged with B. anthracis (Sterne) spores. These substances demonstrate a substantial protective efficacy in combination with ciprofloxacin therapy initiated as late as 48 h post spore challenge, compared to the antibiotic alone. CONCLUSION: Secreted proteolytic enzymes are important pathogenic factors of B. anthrasis, which can be considered as effective therapeutic targets in the development of anthrax treatment and prophylactic approaches complementing anti-lethal toxin therapy

Anticancer Effects and uses of Melatonin A Review

Melatonin (N-acetyl-5-methoxytryptamine, MLT) is a naturally occurring hormone secreted by the pineal gland. Clinical evidence suggests that MLT may have a possible role in the treatment of cancer, where MLT presents many oncostatic properties in a wide variety of tumors, utilizing multiple and converging mechanisms. It is a potent anti-oxidative agent; its circadian rhythm-regulating properties are crucial for orchestrating patterns of hormone secretion, the imbalance of which is implicated in a wide range of hormonedependent cancers of the reproductive organs. Recent advances in cancer treatment can offer therapeutic alternatives that could reduce the severity of unwanted side effects. Several observational studies have demonstrated a relationship between long-term disruption of circadian rhythm with decreased MLT secretion and increased cancer risk, whilst clinical evidence supports the possible benefits from MLT on the survival in patients with a range of cancers. This review will address some of the multiple anticancer properties of MLT, with a particular focus on the mechanisms counteracting tumor occurrence, growth, and development. Recent research into the oncostatic effects of MLT and the mechanisms of action explaining its efficiency for tumor regulation are summarized in this review and suggestions for the therapeutic use of MLT will be presented

Novel avian paramyxovirus isolated from gulls in Caspian seashore in Kazakhstan.

Three isolates APMV/gull/Kazakhstan/5976/2014, APMV/gull/Kazakhstan/ 5977/2014 and APMV/gull/Kazakhstan/5979/2014, were obtained from independent samples during annual surveillance for avian influenza and paramyxoviruses in wild birds from the Caspian Sea coast in Western Kazakhstan, and were initially identified as putative paramyxoviruses on the basis of electron microscopy. Hemagglutination Inhibition Assays with antisera to nine known APMV serotypes (APMV1-9) indicated no relation to any of them. Next generation sequencing of whole genome sequences indicated the three isolates were genetically identical, and had a nucleotide structure typical for all APMVs, consisting of six genes 3'-NP-P-M-F-HN-L-5'. Phylogenetic analyses, and assessment of amino acid identities, suggested the most closely related lineages to be APMV-2, 8, 10 and 15, but the novel isolate had less than 64% identity to them and all other known avian paramyxoviruses. This value was above levels considered to generally define other APMV serotypes. Estimates of the evolutionary divergence of the nucleotide sequences of the genomes of APMVs have shown that novel Kazakhstan APMV strain was closest to APMV-2, APMV-8, APMV-10 and APMV-15, with calculated distance values of 2.057, 2.058, 2.026 and 2.286 respectively, which is above values considered to differentiate other serotypes (observed minimum was 1.108 between APMV-1 and recently isolated APMV/UPO216/Korea). Together, the data suggest that isolate APMV/gull/Kazakhstan/5976/2014 and other two should be considered as the first representative of a novel APMV-20 group, and is the first time that avian paramyxoviruses have been found infecting members of the gull family, extending the known taxonomic host range

ОСОБЕННОСТИ МЕДИАВОСПИТАНИЯ В УСЛОВИЯХ ГЛОБАЛИЗАЦИИ И ИНФОРМАТИЗАЦИИ ОБЩЕСТВА

Abstract. The article focuses on the development of media education in the context of globalization and the information society. The author shows that these processes have both positive and negative affects. Negative aspects of globalization include the destruction of the secular humanist traditions. The author considers the essence, content and methodology of construction and heuristic value of media education. Attention is paid on expanding the traditional means and methods of education through the use of modern media and new educational tools and technologies that repeatedly increasing the educational potential of the subjects of education. Аннотация. В статье речь идет о развитии медиавоспитания в условиях глобализации и информатизации общества. Автор показывает, что эти процессы оказывают как позитивное, так и негативное влияние. К негативным аспектам глобализации относится разрушение вековых гуманистических традиций народа. Раскрывается сущность, содержание, методология построения и эвристическая ценность медиавоспитания. Уделяется внимание и вопросам расширения традиционных средств и методов воспитания через использование современных медиасредств и новых воспитательных технолологий, многократно увеличивающих воспитательный потенциал субъектов образования-воспитания.

Significantly reduced CCR5-tropic HIV-1 replication in vitro in cells from subjects previously immunized with Vaccinia Virus

<p>Abstract</p> <p>Background</p> <p>At present, the relatively sudden appearance and explosive spread of HIV throughout Africa and around the world beginning in the 1950s has never been adequately explained. Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization, we undertook a comparison of HIV-1 susceptibility in the peripheral blood mononuclear cells from subjects immunized with the vaccinia virus to those from vaccinia naive donors.</p> <p>Results</p> <p>Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1α, MIP-1β and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge.</p> <p>Discussion</p> <p>Since primary HIV-1 infections are caused almost exclusively by the CCR5-tropic HIV-1 strains, our results suggest that prior immunization with vaccinia virus might provide an individual with some degree of protection to subsequent HIV infection and/or progression. The duration of such protection remains to be determined. A differential elaboration of MIP-1α, MIP-1β and RANTES between vaccinated and unvaccinated subjects, following infection, does not appear to be a mechanism in the noted protection.</p

Современные приоритеты образовательной политики (Республика Казахстан)

The research is aimed at modern educational policy of the Republic of Kazakhstan in order to consider tendencies of education development in the situation of modern reforms. The authors consider the concept “educational policy” (epistemological aspect) developed in modern social philosophy and they try to demonstrate social processes where educational system is being reformed (ontological aspect). The problems of modern priorities of educational policy in Kazakhstan are considered to be important due to fundamental changes in social relations and transvaluation of moral values and negative developments in society. The paper shows relation of modern process specifics to the country transfer to liberal social structure, the system of capitalist and market relations. Collapse of economic system, education and transvaluation of values were caused by the transfer of Kazakhstan to liberal social structure. Transvaluation of values (axiological aspect of problem study) in people consciousness met transfer from Soviet directive culture to the open and mainstream culture; from learner-centred education to the competence-pragmatic one. The article describes social stratification of society, its being enhanced and escalated by moral stratification. Here the authors mean that consciousness of one part of society is involved in memories of the past while the other part of society is involved in searching moral priorities of the future. The paper underlines that successful overcoming negative development and revival of Kazakhstan as a geopolitical member are impossible without overcoming conscious ness contradiction and fixing general human values in people consciousness. The article attempts considering the main priorities in educational policy of Kazakhstan; their implementation has allowed building new educational system over the past two decades and has adapted it to significant challenges of a new type. The authors analyze the following priorities of educational policy: favorable socio-economic and cultural environment as fundamentals of moral values revival and the source of personality development, enhancement of structure and components of educational system, keeping and expressing of national educational features, eternal traditions etc.Реферат. Цель настоящего исследования - современная образовательная политика Республики Казахстан для понимания тенденций развития системы образования в современных условиях ее реформирования. Опираясь на понятие «образовательная политика» (эпистемологический аспект), разработанное в современной социальной философии, авторы статьи стремятся показать социальные процессы, в которых осуществляется реформирование современной системы образования (онтологический аспект). Важность обозначенных в статье проблем, связанных с современными приоритетами образовательной политики Республики Казахстан, обусловлена кардинальными изменениями казахстанского общества, коренной перестройкой социальных отношений, переоценкой духов ных ценностей и накоплением негативных явлений в обществе. Показано, что современная специфика процесса связана с переходом Казахстана к либеральной модели общественного устройства, к системе капиталистических, рыночных отношений, что вызвало развал отлаженной системы экономической жизни, воспитания и образования, переоценку устоявшихся ценностей. Переоценка ценностей (аксиологический аспект исследования проблемы) в сознании людей совпала с переходом от советской директивной культуры к открытой и массовой, от личностно-ориентированного образования к прагматически-компетентностному. В статье показывается также, что социальное расслоение общества сегодня дополняется и обостряется его духовным расслоением: сознание одной части общества обременено воспоминаниями о прошлом, другой - увлечено поиском духовных ориентиров будущего. Без преодоления противоречивости сознания, без утверждения в сознании людей общечеловеческих ценностей невозможно преодоление негативных явлений, успешное возрождение Казахстана в качестве геополитического субъекта. Предпринята попытка осмыслить основные приоритеты образовательной политики Республики Казахстан, реализация которых позволила буквально за два десятилетия выстроить новую образовательную систему и адаптировать ее к существенным вызовам современности. Анализируются такие приоритеты образовательной политики, как создание благоприятной социально-экономической и культурной среды как объективной основы возрождения духовных ценностей и определяющего источника дальнейшего личностного развития, совершенствование самой структуры и содержания образовательной системы, сохранение и воспроизводство национальных черт образования (воспитания), вековечных позитивных традиций и др

The effects of antiviral treatment on breast cancer cell line

Background: Recent studies have revealed the positive antiproliferative and cytotoxic effects of antiviral agents in cancer treatment. The real effect of adjuvant antiviral therapy is still controversial due to the lack of studies in biochemical mechanisms. Here, we studied the effect of the antiviral agent acyclovir on morphometric and migratory features of the MCF7 breast cancer cell line. Molecular levels of various proteins have also been examined. Methods: To evaluate and assess the effect of antiviral treatment on morphometric, migratory and other cellular characteristics of MCF7 breast cancer cells, the following experiments were performed: (i) MTT assay to measure the viability of MCF7 cells; (ii) Colony formation ability by soft agar assay; (iii) Morphometric characterization by immunofluorescent analysis using confocal microscopy; (iv) wound healing and transwell membrane assays to evaluate migration and invasion capacity of the cells; (v) ELISA colorimetric assays to assess expression levels of caspase-3, E-cadherin and enzymatic activity of aldehyde dehydrogenase (ALDH). Results: We demonstrate the suppressive effect of acyclovir on breast cancer cells. Acyclovir treatment decreases the growth and the proliferation rate of cells and correlates with the upregulated levels of apoptosis associated cytokine Caspase-3. Moreover, acyclovir inhibits colony formation ability and cell invasion capacity of the cancer cells while enhancing the expression of E-cadherin protein in MCF7 cells. Breast cancer cells are characterized by high ALDH activity and associated with upregulated proliferation and invasion. According to this study, acyclovir downregulates ALDH activity in MCF7 cells. Conclusions: These results are encouraging and demonstrate the possibility of partial suppression of cancer cell proliferation using an antiviral agent. Acyclovir antiviral agents have a great potential as an adjuvant therapy in the cancer treatment. However, more research is necessary to identify relevant biochemical mechanisms by which acyclovir induces a potent anti-cancer effect

A computational model for suspensions of motile micro-organisms in the flow of ferrofluid

The performance of friction drag, heat transfer rate, and mass transfer is illustrated the in boundary layer flow region via density of motile microorganisms. Magnetic dipole in presence of Curie temperature and density of motile microorganisms plays important role in stabilizing and controlling the momentum and thermal boundary layers. In this direction, the characteristics of the magnetic dipole on the suspensions of motile microorganisms in the flow of ferrofluid are incorporated. Heat flux in the suspensions of motile microorganisms and at the surface is computed via Fourier's law of heat conduction. Characteristics of sundry physical parameter on the ferrohydrodynamic, thermal energy, mass transfer, and bioconvection are computed numerically and analytically. It is depicted that an enhancement in thermal Rayleigh number results in the reduction of friction drag, thereby enhances the heat transfer rate and Sherwood number at the surface, while the local density of motile microorganisms enhance for larger values of bioconvection Lewis number. Further, it is characterized that bioconvection Rayleigh number has increasing behavior on the heat transfer in the boundary layer. Comparison with available results are found in an excellent agreement.This paper was funded by the Higher Education Commission, Pakistan (HEC), under grant no. 6170/Federal/NRPU/R&D/HEC/2016 . It was also supported by the Higher Education Commission, Islamabad, Pakistan - award of scholarship “ International Research Support Initiative Program ” grant No: I-8/HEC/HRD/2018/8972 , PIN: IRSIP 41 PSc 28, for Texas A&M University, USA

Analysis of non-newtonian magnetic casson blood flow in an inclined stenosed artery using caputo-fabrizio fractional derivatives

Background and Objective: Arterial diseases would lead to several serious disorders in the cardiovascu- lar system such as atherosclerosis. These disorders are mainly caused by the presence of fatty deposits, cholesterol and lipoproteins inside blood vessel. This paper deals with the analysis of non-Newtonian magnetic blood flow in an inclined stenosed artery. Methods: The Casson fluid was used to model the blood that flows under the influences of uniformly dis- tributed magnetic field and oscillating pressure gradient. The governing fractional differential equations were expressed using the Caputo Fabrizio fractional derivative without singular kernel. Results: The analytical solutions of velocities for non-Newtonian model were then calculated by means of Laplace and finite Hankel transforms. These velocities were then presented graphically. The result shows that the velocity increases with respect to Reynolds number and Casson parameter, while decreases when Hartmann number increases. Conclusions: Casson blood was treated as the non-Newtonian fluid. The MHD blood flow was accelerated by pressure gradient. These findings are beneficial for studying atherosclerosis therapy, the diagnosis and therapeutic treatment of some medical problems