Особливості зображення образу коханої в інтимній ліриці Григорія Чупринки (Features of the image of cohana in immediate lyrics Grigoria Chuprynki)

У статті аналізується поезія Григорія Чупринки, де було розглянуто образ коханої жінки ліричного героя. Відтворено портрет героїні; розкрито символіку її асоціативних образів, основні риси характеру. Визначено для поетичної практики автора засоби творення художнього образу, а також його стильові особливості в любовній ліриці. (The article analyzes the poetry of Grigoria Chuprinky, where the image of the beloved woman of the lyrical hero was considered. With insuffi cient study of the love lyrics of Grigoria Chuprinky, it can be argued that the theme of love occupied an important place in the work of the artist. In the poetry, the author does not depict the physical image of the woman himself, but her presence is quite tangible, and thanks to the caressful words, we feel the sincerity and tenderness of the feelings of a lover. Poetry is permeated with the motive of cleansing from sin as a «sacred love» of a beloved, and love acts as the only feeling that is able to atone for all the sins of the earth. In order to reveal the image of a beloved author as much as possible, and to the musicality of poetry, through the combination of assonances and alliterations, he forms the elegiac mood of the poem. In the manner of his beloved, Chuprinka combined the best features: she is beautiful, her character is changing, and in addition she hopes to realize a cherished dream. However, the image of a woman is quite contrasted and ambiguous: she is able to heal the mental wounds of her husband, while, at the same time, she may mortally strike his eyes with her eyes. The author is using the contrast: creates a portrait of a woman from the inside, based on the psychological depth and mystery of herinner world. A portrait of a heroine is restored; the symbols of its associative images, the main features of the character are revealed. The poetic practice of the author of the means of creating an artistic image, as well as his stylistic features in love poetry, is determined.

Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases.

Autophagy is a major, conserved cellular pathway by which cells deliver cytoplasmic contents to lysosomes for degradation. Genetic studies have revealed extensive links between autophagy and neurodegenerative disease, and disruptions to autophagy may contribute to pathology in some cases. Autophagy degrades many of the toxic, aggregate-prone proteins responsible for such diseases, including mutant huntingtin (mHTT), alpha-synuclein (α-syn), tau, and others, raising the possibility that autophagy upregulation may help to reduce levels of toxic protein species, and thereby alleviate disease. This review examines autophagy induction as a potential therapy in several neurodegenerative diseases-Alzheimer's disease, Parkinson's disease, polyglutamine diseases, and amyotrophic lateral sclerosis (ALS). Evidence in cells and in vivo demonstrates promising results in many disease models, in which autophagy upregulation is able to reduce the levels of toxic proteins, ameliorate signs of disease, and delay disease progression. However, the effective therapeutic use of autophagy induction requires detailed knowledge of how the disease affects the autophagy-lysosome pathway, as activating autophagy when the pathway cannot go to completion (e.g., when lysosomal degradation is impaired) may instead exacerbate disease in some cases. Investigating the interactions between autophagy and disease pathogenesis is thus a critical area for further research

Neurodegenerative Diseases and Autophagy

Most neurodegenerative diseases are characterized by the accumulation of aggregated proteins within neurons. These aggregate-prone proteins cause toxicity, a phenomenon that is further exacerbated when there is defective protein clearance. Autophagy is an intracellular clearance pathway that can clear these protein aggregates and has been shown to be beneficial in the treatment of neurodegenerative diseases in a variety of model systems. Here, we introduce the key components of the autophagy machinery and signaling pathways that control this process and discuss the evidence that autophagic flux may be impaired and therefore a contributing factor in neurodegenerative disease pathogenesis. Finally, we review the use of autophagy upregulation as a therapeutic strategy to treat neurodegenerative disorders

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Molecular changes in the postmortem parkinsonian brain

Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's-linked genes; Transition metals, calcium and calcium-binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways

Вакцины с адъювантами. Доклинические исследования

The paper presents the data on safety and efficacy assessment of adjuvants and vaccines with adjuvants at the stages of development and preclinical studies based on international recommendations. The presence of an adjuvant in vaccine content ensures higher expressing and prolonged specific immunity. The origin and nature of adjuvants currently used for various vaccines are different. Adjuvants can be classified by origin, mechanism of action, physical and chemical properties. The finished vaccine may contain one or more adjuvants which can be intended for one antigen or a number of antigens in vaccine content. Antigen-adjuvant combination is a key part in the production of a vaccine with an adjuvant. Due to the diversity of adjuvant nature and their physical and chemical properties and mechanisms of action, as well as to antigens in adjuvant vaccines content, it is rather complicated to plan and to conduct preclinical studies. The present article describes various aspects of preclinical studies of adjuvants and vaccines with adjuvants based on the analysis of current guidelines and requirements.Изучение адъювантов берет начало с 20-х годов XIX века, когда Гастон Рамон показал возможность усиления гуморального иммунного ответа на дифтерийный и столбнячный анатоксины с помощью введения дополнительных веществ - адъювантов [1]. Адъюванты используют для повышения иммуногенности высокоочищенных бактериальных и вирусных антигенов, анатоксинов, рекомбинантных и синтетических антигенов и др. Включение адъювантов в состав вакцин обеспе чивает более быстрое формирование выраженного и длительного специфического иммунитета. Целесообразность использования адъювантов в вакцинах заключается в повышении иммуногенности вакцин, изменении характера иммунного ответа, снижении количества антигена, необходимого для успешной иммунизации, уменьшении кратности введения вакцины и повышении интенсивности иммунного ответа у лиц со сниженной иммунологической активностью, в том числе у пожилых лиц [2-5]. Є В настоящей работе представлены материалы по оценке безопасности и эффективности адъювантов и вакцин с адъювантами на этапах их разработки и проведения доклинических исследований на основе международных рекомендаций. Включение адъювантов в состав вакцин обеспечивает формирование более выраженного и длительного специфического иммунитета. Происхождение и природа адъювантов, используемых в настоящее время для разных вакцин, различны. Адъюванты могут быть классифицированы по происхождению, механизму действия, физико-химическим свойствам. Готовая вакцина может содержать как один, так и несколько адъювантов, которые могут быть предназначены для одного антигена или разных антигенов, входящих в состав вакцины. Объединение антигена с адъювантом является ключевым моментом при получении вакцины с адъювантом. Ввиду большого разнообразия природы адъювантов, их физико-химических свойств и механизмов действия, а также антигенов, входящих в состав вакцин с адъювантами, планирование и проведение доклинических исследований представляется достаточно сложным. В данной статье приведены различные аспекты доклинического изучения адъювантов и вакцин с адъювантами на основании анализа современных методических рекомендаций и требований

Development of Professional Judicial Corporation in Russia in XVIII–XXI centuries

The article introduces a comprehensive analysis of professional judicial corporation in Russia in the XVIII–XXI centuries in its theoretical and historical aspects. The research objective was to clarify the concept and categories of judicial power, as well as to model the process of its development in Russia. The issue of professions and professional corporations as social phenomena is a matter of sociology. For lawyers, sociological studies are important in connection with the issue of judicial corporation development, i.e., its theoretical and historical development. The author relied on the structural and functional approach to the professionalization model developed by sociologist G. Vilensky, who interpreted the categories of judicial profession, judiciary, and judicial corporation. The authors revealed the directions in the development of the professional judicial corporation in Russia in the XVIII–XXI centuries and periodized this process. A separate and permanent judicial function determined the emergence of professional judiciary, organizationally represented by a professional judicial corporation. The profession of a judge is all these elements combined. The judicial corporation developed in Russia in three directions, i.e., normative, organizational, and symbolic, with a prominent regulatory influence of the state. The judicial profession and professional corporation started to develop in Russia during the judicial reforms in the XVIII century. This slow, nonlinear, and discrete process was completed as late as in the XXI century with all the necessary stages of professionalization: the professional corporation finally became the organization form of the Russian judiciary. The authors revealed five stages in the history of the professional judicial corporation in Russia: 1) XVIII century; 2) the first half of the XIX century; 3) 1864–1917; 4) 1917–1989; 5) 1989 – early XXI century