Death receptors: New opportunities in cancer therapy

© 2017 Park-media, Ltd. This article offers a detailed review of the current approaches to anticancer therapy that target the death receptors of malignant cells. Here, we provide a comprehensive overview of the structure and function of death receptors and their ligands, describe the current and latest trends in the development of death receptor agonists, and perform their comparative analysis. In addition, we discuss the DR4 and DR5 agonistic antibodies that are being evaluated at various stages of clinical trials. Finally, we conclude by stating that death receptor agonists may be improved through increasing their stability, solubility, and elimination half-life, as well as by overcoming the resistance of tumor cells. What's more, effective application of these antibodies requires a more detailed study of their use in combination with other anticancer agents

Deimination of the myelin basic protein decelerates its proteasome-mediated metabolism

© 2016, Pleiades Publishing, Ltd.Deimination of myelin basic protein (MBP) by peptidylarginine deiminase (PAD) prevents its binding to the proteasome and decelerates its degradation by the proteasome in mammalian cells. Potential anticancer drug tetrazole analogue of chloramidine 2, at concentrations greater than 1 µM inhibits the enzymatic activity of PAD in vitro. The observed acceleration of proteasome hydrolysis of MBP to antigenic peptides in the presence of PAD inhibitor may increase the efficiency of lesion of the central nervous system by cytotoxic lymphocytes in multiple sclerosis. We therefore suggest that clinical trials and the introduction of PAD inhibitors in clinical practice for the treatment of malignant neoplasms should be performed only after a careful analysis of their potential effect on the induction of autoimmune neurodegeneration processes

Myelin-Reactive Monoclonal Antibodies from Multiple Sclerosis Patients Cross-React with Nucleoproteins in HEp-2 Lysate

© 2016, Springer Science+Business Media New York.Autoimmune disorders are characterized by appearance of self-reactive species of immune system such as T cells, B cells and antibodies. For the majority of autoimmune pathologies the list of specific autoantigens is known. Myelin basic protein (MBP) is one of the most important autoantigens in multiple sclerosis (MS), which destruction is a hallmark of disease progression. Antibodies toward MBP are found in serum and cerebrospinal fluid of MS patients. Here we investigated whether monoclonal human MBP-specific antibodies selected from MS patients repertoire cross-react with other autoimmune markers. For this purpose we performed Western blot analysis of recombinant anti-MBP antibodies with HEp-2 cell lysate. Our data suggest existence of enhanced level of cross-reactivity of anti-MBP antibodies with ribonucleoprotein A (RNP A), a marker of Sharp’s syndrome and systemic lupus erythematosus, ribosomal P protein (Rib. P-Prot), a marker for systemic lupus erythematosus, and centromere protein A/B (CENP A/B), markers for progressive systemic sclerosis

Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF- α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients

© 2016 Yakov Lomakin et al.We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys) effectively suppressed experimental allergic encephalomyelitis (EAE). Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials

mRNA expression profile of mouse oligodendrocytes in inflammatory conditions

© 2016, Pleiades Publishing, Ltd.In this study, we performed transcriptome profiling of oligodendrocyte culture of mice treated with the remyelinating therapeutic agent benztropine in the presence and absence of interferon gamma (IFNγ). The results of this work are important for understanding the expression profile of oligodendrocytes under conditions of systemic inflammation in the central nervous system in multiple sclerosis as well as the mechanisms of cellular response to benztropine in light of its possible use for the treatment of multiple sclerosis

Результаты лечения пациентов с экстравазальной компрессией чревного ствола и атеросклеротическим его поражением

Introduction. Extravasal compression of celiac trunk is the cause of chronic abdominal ischemia syndrome (CAIS) along with atherosclerotic lesions of the visceral branches of the aorta. Patients with isolated compression and those in the older age group with compression combined with atherosclerotic lesion are distinguished. At present, the issues of indications for surgical treatment the pattern and technique of surgical intervention as well as the evaluation of decompression results in the early and distant postoperative period remain controversial and unsolved.Aim. The aim of our study was to determine indications and contraindications for surgical intervention, to improve the technique of the surgery, to evaluate and find ways to improve the closest and most distant results of laparoscopic decompression of the celiac trunk.Materials and methods. The article discusses the experience of performing 27 laparoscopic decompressions of the celiac trunk and the results of examination and treatment of 5 patients who underwent endovascular interventions due to a combined lesion -extravasal compression of the celiac trunk and atherosclerotic occlusion. Intraoperative laparoscopic ultrasound was performed in all cases of the celiac trunk decompression to determine the celiac trunk topography and assess the adequacy of its decompression.Results. The average duration of the surgery was 92 minutes. Intraoperative and early postoperative complications were not observed. Intraoperative blood loss didn't exceed 50 ml. Average duration of stay in the hospital was 5 days. According to the data of ultrasound examination, the average degree of celiac trunk compression before the operation was 76%, in the early postoperative period it decreased to 43%, and in the distant period it decreased to 32%.Discussion. Based on our experience, the key to successful management of patients with celiac trunk compression syndrome is a multidisciplinary approach to diagnosis and treatment. Patients need thorough differential diagnosis, including psychoneurologist consultation. Experience in treating patients with atherosclerotic lesions of the celiac trunk combined with extravasal compression has shown good immediate and distant decompression results and adverse results of the first stage of endovascular interventions.Conclusion. Laparoscopic decompression of the celiac trunk is an effective treatment method in patients without atherosclerotic lesions.Введение. Экстравазальная компрессия чревного ствола является причиной синдрома хронической абдоминальной ишемии (СхАИ) наряду с атеросклеротическим поражением висцеральных ветвей аорты. Выделяются пациенты, имеющие изолированную компрессию, и пациенты, относящиеся к старшей возрастной группе, имеющие компрессию в сочетании с атеросклеротическим поражением. В настоящее время спорными и нерешенными остаются вопросы показаний к хирургическому лечению, характера и техники оперативного вмешательства, а также оценки результатов декомпрессии в раннем и отдаленном послеоперационном периодах.Цель. Целью нашего исследования являлось определение показаний и противопоказаний к выполнению оперативного вмешательства, усовершенствование техники операции, оценка и поиски путей улучшения ближайших и отдаленных результатов лапароскопической декомпрессии чревного ствола.Материалы и методы. В статье рассматривается опыт выполнения 27 лапароскопических декомпрессий чревного ствола и результаты обследования и лечения 5 пациентов, перенесших эндоваскулярные вмешательства по поводу сочетанного поражения - экстравазальной компрессии чревного ствола и атеросклеротической окклюзии. Интраоперационное лапароскопическое УЗИ выполнялось во всех случаях декомпрессии чревного ствола для определения топографии чревного ствола и оценки адекватности его декомпрессии.Результаты. Средняя продолжительность операции составляла 92 мин. Интраоперационных осложнений и осложнений в раннем послеоперационном периоде не отмечено. Интраоперационная кровопотеря не превысила 50 мл. Средняя длительность пребывания в стационаре составила 5 дней. По данным ультразвукового исследования, средняя степень сужения чревного ствола до операции составляла 76%, в раннем послеоперационном периоде уменьшилась до 43%, а в отдаленном периоде снизилась до 32%.Обсуждение. Исходя из нашего опыта, ключом к успешному ведению пациентов с синдромом компрессии чревного ствола является мультидисциплинарный подход к диагностике и лечению. Пациенты нуждаются в тщательной дифференциальной диагностике, включая консультацию психоневролога. Опыт лечения пациентов, имеющих атеросклеротическое поражение чревного ствола в сочетании с экстравазальной компрессией, показал хорошие ближайшие и отдаленные результаты декомпрессии и неблагоприятные результаты выполненных первым этапом эндоваскулярных вмешательств.Заключение. Лапароскопическая декомпрессия чревного ствола является эффективным методом лечения у пациентов, не имеющих атеросклеротического поражения

INVESTIGATION OF THE INFLUENCE OF PROCESS CONDITIONS AND PROPERTIES OF THE MEDIUM ON THE KINETICS OF THE SWELLING OF GREEN BUCKWHEAT FLAKES

The chemical composition of green buckwheat flakes, especially swelling of the flakes at different process conditions. The process of swelling depends on the nature of the high molecular compound, temperature, composition and pH of the absorbing liquid and can flow unrestricted and restricted. With a limited degree of swelling of the swelling reaches the limit and is no longer changing. As a result of limited swelling formed jelly. If the limit value of the degree of swelling in contact with a further high-molecular compound and a solvent is reduced, there is an unlimited swelling. In this case, the swelling of the first stage of dissolution. Unlimited swell polymers with weak intermolecular bonds. Character of the process has an impact on quality indicators and semi-finished products. The resulting kinetic curves indicate limited swelling main components of green buckwheat flakes in all test solutions. In the alkaline pH range, partial dissolution occurred certain components, but the general nature of the process is not appreciably affected. The paper identified the maximum degree and the rate constant swelling green buckwheat flakes in solutions with different pH. To quantify the extent and limit of the rate constant swelling high-molecular compound at different process conditions (type of solvent, temperature, pH) determine the degree of swelling at specified intervals and construct the kinetic curve swelling. The acidity of the medium affects mainly on swelling polyampholytes, which are the proteins that make up most of the swell components flakes green buckwheat. Depending on the pH of the protein macromolecule adopt different conformations. The minimum degree of swelling of the protein corresponds to its isoelectric point at which stipulates equality of positive and negative charges in the macromolecule and it rolled into a ball or globule, which hinders the penetration of solvent molecules into the matrix of high-molecular compound. Comparison of the rate constant swelling possible to determine the maximum rate of swelling. In this paper we measured the specific heat integral swelling swelling fraction flakes green buckwheat and calculated mass of water adsorbed macromolecular substances on the hydration step, set its share in the total mass of liquid absorbed

Algorithm of actions to identify and reduce risks in the production of milk and plant products

Foods with a new generation of functional and improved consumer properties, corresponds to the modern concepts of nutrition science and consumer needs. functional food production is a major global trend in food science and the subject of innovation. One of the important trends is the use of plant complexes and plant food systems. Using the plant complexes (PC) and plant food systems (PFS) provides a number of benefits: improved consumer properties of the product, do not need to change the process, it is possible to control directional rheological properties and consistency of the finished products, reduced the number of risk points in the production cycle. This paper describes the development of an algorithm of action to identify and mitigate risks in the production of milk and plant products. Also conducted a risk analysis, identified and assessed the risks in the process of production, installed capacity of available resources to reduce the level of risk. Established and submitted to the critical control points in production processes, as well as the critical limits for each critical control points, and the procedure for corrective action in case of violations of the past. During the study, measured changes in the quantitative and qualitative composition of microflora of semi-finished and Quantity of Mesophilic Aerobic and Facultative Anaerobic Microorganisms (QMAFAnM). To determine QMAFAnM samples were taken: 1 – cheesecakes (control), 2 – cheesecakes with RPS. Microbiological studies analyzed frozen-conjugated semi-finished products was determined within 90 days. It is clear from the data that the cottage cheese with semi-finished products have a lower RPM 11.7%. Analyzing the data, it is possible to conclude that the physico-chemical, organoleptic and microbiological indicators of products was developed to set standards on cheese semi-finished products. multilevel structure that characterizes the quality indicators has been developed and is presented on the basis of the survey. The developed algorithm for monitoring critical control points on the complex and the individual indicators will improve the quality and safety evaluations of new food products

Physiological features of aggregation of the main formed elements of blood in calves at the beginning of early ontogenesis

The need to intensify milk production urgently dictates the need to continue research on the physiology of cattle of any age. It is customary to attach great importance to blood, consisting of uniform elements and plasma, constantly circulating through the vessels. It provides gas exchange, metabolism and the delivery of hormones and bioregulators in their tissues. The success of hemocirculation strongly determines the completeness of the realization of the genetic growth potential and productivity of the animal and is closely related to the activity of aggregation of blood cells. Purpose: to find out the activity of aggregation of the main formed elements of the blood in newborn calves. The work was carried out on 32 newborn calves of black-motley breed, born of healthy cows after 2–3 pregnancies. The calves were examined on 1–2, 3–4, 5–6, 7–8 and 9–10 days of life. In the work, hematological and statistical research methods are applied. For newborns in calves, a tendency towards increased aggregation activity of red blood cells was revealed. This was combined with a low platelet aggregation, which tended to increase. The low aggregation of neutrophils in these calves also gradually increased. In newborn calves of optimal physiological status, there is a tendency to increase the aggregation of the main formed elements of the blood, which is a response to environmental influences

Herbal complex of green buckwheat in the production technology of cakes

The possibility of using vegetable complex of green buckwheat in production technology cheesecakes. The unique chemical, rich mineral and vitamin composition buckwheat green indicates desirability of not only its use, but also th e possibility of using for cooking preventive and functional orientation. Using green buckwheat plant complex due to the hi gh water-holding ability to reduce the time of the process, eliminate some technological preparatory operations, such as pressing off. It is found that the maximum degree of swelling (2.5 g/g) was observed at 40 oC and pH 4, 2. The time to reach an equilibrium state is reached after 30 minutes. On the basis of the research has been defined in a way to make plant complex curd basis, in an amount of from 10 to 70 % based on standardized physical-chemical and organoleptic characteristics of harmonious order to minimize-if-operation of flour to make the product functional and preventive properties. Technology of production of a pre -from adequate use of shock freezing, thus preserving the shape, color and flavor of the product. Microbiologists -cal studies analyzed frozen semi-finished products indicates that the microbiological-cal indicators remain stable throughout the shelf life. The use of herbal ingredients in the development of technology and the adjustment of the nutritional value of cheese bioproducts will solve the issue of their care-enrichment in essential micronutrients and natural way to improve the taste and increase the life -sti Useful developed products that currently is a modern and topical focus of research