Effect of Lysine Acridone Acetate on the Level of Apoptosis and Expression of Apoptosis-Associated Proteins during Antioncogenic Therapy in Colorectal Cancer in Mice.

We studied the mechanism of action of cytostatics with the addition of lysine acridone acetate to evaluate the possibility of its use for improving the effectiveness of antioncogenic therapy in colorectal cancer. In Nude mouse model, the level of apoptosis (TUNEL) and expression of proteins CD95, p53, Bcl-2, histone H3, and Ki-67 (immunohistochemistry) were assessed in primary tumor biopsy specimens. It has been shown that cytostatic treatment led to stimulation of p53-mediated apoptosis and suppression of proliferation (Ki-67 expression) of tumor cells, and apoptosis level was increased in groups receiving lysine acridone acetate.

Neuroinflammatory Dysfunction of the Blood-Brain Barrier and Basement Membrane Dysplasia Play a Role in the Development of Drug-Resistant Epilepsy.

Drug-resistance epilepsy (DRE) is a key problem in neurology. It is possible that damage to the blood-brain barrier (BBB) may affect resistance in DRE. The aim of this work was to assess the damage and dysfunction in the BBB in the area of epileptic foci in patients with DRE under conditions of neuroinflammation.

Relationship between Neuroglial Apoptosis and Neuroinflammation in the Epileptic Focus of the Brain and in the Blood of Patients with Drug-Resistant Epilepsy.

Neuroglial apoptosis and neuroinflammation play an important role in epileptogenesis. The aim of this study is to evaluate neuronal and glial apoptosis in association with neuroinflammation in brain epileptic focus and inflammatory changes in blood in patients with focal drug-resistant epilepsy (DRE). Pathological changes in the temporal lobe in epilepsy (histology, transmission electron microscopy), levels of apoptotic and neuroinflammatory proteins: active caspase-3 (immunohistochemistry), full-length form caspase-3, caspase-9, FAS, FAS-L, NF-kB, TNF-α, p53 (Western blot), and cytokine levels in blood: IL-1β, IL-2, IL-4, IL-7, TNF-α, etc.

Desynchronosis: Types, Main Mechanisms, Role in the Pathogenesis of Epilepsy and Other Diseases: A Literature Review.

Circadian information is stored in mammalian tissues by an autonomous network of transcriptional feedback loops that have evolved to optimally regulate tissue-specific functions. Currently, stable circadian rhythms of the expression of clock genes (, etc.), hormones, and metabolic genes (, etc.

[Mechanisms of apoptosis in drug-resistant epilepsy].

Epilepsy is a chronic neurological disease with regular spontaneous seizures associated with neuroinflammatory, autoimmune and neurodegenerative processes. Approximately 40% of patients suffer from drug-resistant epilepsy, which leads to an increased risk of premature death, injury, irreversible brain damage, psychosocial dysfunction, and reduced quality of life. Apoptosis of neurons and glial cells of the brain is of great importance in the pathogenesis of epilepsy, especially drug-resistant epilepsy.

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review.

Epilepsy is a chronic neurological disorder characterized by recurring spontaneous seizures. Drug resistance appears in 30% of patients and it can lead to premature death, brain damage or a reduced quality of life. The purpose of the study was to analyze the drug resistance mechanisms, especially neuroinflammation, in the epileptogenesis.

[Ultradian rhythms and oxidative stress in the tissue of the lymph nodes in ontogenesis.].

We studied the age-related features of the ultradian rhythms of levels of total protein and albumin in the lymph nodes under normal condition and chronic toxic oxidative stress condition using the chronobiological approach and the biochemical methods. During the experiment, we compared the rhythmic activity of levels of total protein and albumin in the rat lymph nodes in ontogenesis and during chronic exposure to sulfur-containing natural gas. The revealed fluctuations of the levels of total protein and albumin can be characterized as around-hourly (ultradian) rhythms, which period is approximately 20-40 to 60 minutes.

[Cytoflavin effect on locomotor and psychoemotional status in physiological and pathological aging.].

Currently, the actual problem is the correction of motor, cognitive and psychoemotional disorders in physiological aging, as well as in various pathological processes that accompany aging and accelerate it. In this regard, it became necessary to search for drugs that can restore age-related disorders of the brain. The aim of the study was to evaluate the possibility of Cytoflavin as a pharmacological corrector of age-dependent disorders of the functions of the cerebral cortex during physiological and pathological, accelerated aging.

[FAS- and TNF-dependent ways participation in apoptosis mechanisms in hypotalumus in physiological and pathological aging.].

The cell resistance to apoptosis can be related to the activity of cytokine-dependent signaling. So, the aim of the work is to investigate the mechanisms of cytokine-dependent FAS/TNF-mediated regulation of apoptosis of neurosecretory cells in the physiological and pathological (overexpression of the oncogene HER-2/Neu) aging. HER2/Neu transgenic accelerated aged mice of different ages and wild type FVB/N were examined.

Functional Imbalance of Glutamate- and GABAergic Neuronal Systems in the Pathogenesis of Focal Drug-Resistant Epilepsy in Humans.

The mechanisms of the formation of pharmacological resistance in temporal focal epilepsy remain poorly understood, and effective treatment strategies that can suppress epileptogenesis do not currently exist. We studied the imbalance between the glutamatergic (stimulating) and GABAergic (inhibitory) neuronal systems, as well as the role of apoptotic processes in the pathogenesis of drug-resistant epilepsy. To this end, the expression of Gad65, Vglut2, NR2B, Bcl-2, and caspase-8 proteins was analyzed in the gray and white matter of the temporal cortex of human brain.

Analysis of HER-2/neu Receptor Expression and the Level of Neuronal Apoptosis in HER-2/neu Transgenic Mice during Aging.

We studied neuronal death in the sensorimotor cortex, hippocampus, and supraoptic and paraventricular nuclei of the hypothalamus and dynamics of HER-2/neu expression in late ontogenesis in young and old transgenic HER-2/neu mice. Wild-type FVB/N mice served as the control. The intensity of apoptosis (TUNEL) and HER-2/neu expression (Western blotting) in the same brain regions were measured.

[Effects of cytoflavin on neuronal apoptotic processes in the murine cerebral cortex on a model of physiologicaland pathological aging].

Unlabelled: Involutional changes in the cerebral cortex substantially affect the activity of the cortex itself and the function of target organs. This necessitates pharmacological correction of age-related diseases, primarily a high level of cell death.

Objective: To investigate the role of cytoflavin in mechanisms for the apoptotic regulation of cerebral cortical cells during physiological and pathological aging (in the presence of HER-2/neu overexpression).

[Pharmacological correction of alterations of apoptosis of the neurons of the hypothalamus suprachiasmatic nucleus and pinealocytes during aging and stress.].

As is known, the pineal gland plays an important role in adaptogenesis, and the hypothalamus is one of the main links of the stress-reactive system and is involved in the regulation of the involution of the whole organism. So, the study of changes in these organs during stress and aging is very interesting. The aim of the work is to study the mechanisms of apoptosis of pinealocytes and neurosecretory cells of the suprachiasmatic nucleus of the hypothalamus during aging, stress, and under the conditions of pharmacological correction of involutional processes and stress response (antioxidant alpha-tocopherol acetate, immunomodulator cycloferon).

The role of STAT transcription factors in apoptosis regulation of hypothalamic neurons in aging in HER-2/neu transgenic mice and wild-type FVB/N mice.

For the firsts time, the involvement of the STAT pathway in the regulation of neuronal apoptosis in physiological aging and in old mice overexpressing the HER-2/neu oncogene was studied. We showed that suppression of STAT3, STAT5, and STAT6 and overexpression of the proapoptotic factor STAT1, which provides p53-mediated apoptosis, are the causes for increasing the number of apoptotic neurons in physiological aging. HER-2 tyrosine kinase receptor overexpression promotes neuronal survival through activation of STAT-signaling pathway with simultaneous suppression of the proapoptotic factor STAT1.

[PHARMACOLOGICAL CORRECTION OF APOPTOSIS LEVEL OF CORTICAL NEURONS IN AGED HER2/NEU TRANSGENIC MICE].

Neurodegenerative changes and neuronal death are the basis for development of the nervous system aging. We investigated the mechanism of apoptosis of the sensorimotor cortex neurons of transgenic mice HER2/neu during aging, changes in the cortex function and the participation of exogenous neurometabolites (cytoflavin, piracetam) in regulation of neuronal death and locomotor and psycho-emotional status of mice. The level of apoptosis and expression of apoptosis markers (TUNEL, immunohistochemistry, Western blotting) in HER2/neu transgenic mice as compared to wild type mice (FBV line) were determined.

[Comparative experimental study of the influence of drugs that improve brain metabolism (angiogen, cytoflavin) on neuronal apoptosis and function of cerebral cortex during aging].

The safety of cortical neurons and their functional activity is essential for organism at all stages of ontogenesis. However, aging changes leading to an increase in apoptosis level may cause considerable damage to cerebral cortex function, including sensorimotor. We have studied the role of exogenous neurometabolites (angiogen, cytoflavin) in apoptosis regulation and correction of age-related motor and behavioral disturbances.

Pathways of apoptosis regulation in hepatocytes induced by first-line antitubercular drugs.

We studied pathways of apoptosis regulation during experimental hepatopathy caused by treatment with antitubercular drugs and involvement of some hepatoprotectors and immunomodulators in the regulation of hepatocyte apoptosis induced by antitubercular drugs. The intensity of apoptosis and expression of apoptosis-associated molecules were evaluated. It was shown that antitubercular drugs induce apoptosis in hepatocytes by triggering external signaling pathway and p53-dependent signaling pathway and simultaneously reducing the level of anti-apoptotic Bcl-2 protein.

[Role of hepatoprotectors and immunomodulators in regulation of hepatocyte apoptosis induced by antituberculosis treatment].

Unlabelled: It was currently shown that hepatopathy due to drug toxicity is associated with increased apoptosis of hepatocytes. Therefore, development of drugs which regulate cell death is of great importance.

Aim: To involve some hepatoprotectors (ademethionine, reamberin, remaxol) and immunomodulators (cycloferon) into regulation of apoptosis in experimental models of liver first-line antituberculousis drugs (isoniazid, rifampicin, pyraztinamide).

[Mechanism of hepatocyte apoptosis in experimental toxic liver injury].

One of the causes of drug hepatopathy is hepatocyte apoptosis, the mechanisms of which are still unclear. The experiments were performed in 24 Wistar rats to study the role of hepatoprotectors in the regulation of hepatocyte apoptosis in liver damage induced by administration of antituberculosis drugs (ATD). The level of apoptosis (TUNEL) was evaluated, and the expression of apoptosis-associated molecules was detected by immunohistochemistry and Western blotting.

[Role of cycloferon and interferon-alphain apoptosis regulation in neuroendocrinal system on aging].

A detailed analysis of the literature data gives contradictory information about the role of interferon-alpha in the regulation of apoptosis, while there are almost no data on the participation of cycloferon in this process. Results of original experiments in recent years showed that exogenous interferon-alpha is not apoptosis protector in hypothalamic neurons on aging. The treatment with interferon-alpha activates dystrophic processes in neurosecretory cells of aged mice.

[Cycloferon: mechanism of action, functions and application].

In recent years, both interferons and inductors of endogenous interferon production find increasing use in clinical practice. The latter agents are characterized by high antiviral and immunomodulatory activity in the absence of serious side effects, which makes it possible to prescribe long courses if necessary. One of the most frequently used interferon inductors is cycloferon.

[Apoptosis of the hypothalamus neurosecretory cells in stress and ageing: the role of immune modulators].

There is assumption about active role of immune modulators in cell death process. The involvement of interferon-alpha and cycloferon in apoptosis regulation of hypothalamic neurons of mice during stress and aging was studied. We determined the expression of apoptosis markers (Bcl-2, Mcl-1, Bax) in comparison with apoptosis level.

[Influence the water deprivation and alpha-tocopheroli acetates on the expression of apoptosis regulator proteins].

We revealed ontogenetic features in apoptosis level, apoptosis signal proteins expression, antioxidant (alpha-tocoferoli acetate) effects in neurons of magnocellular hypothalamic centers of BALB-c mice. It was obtained that water deprivation stress leads to apoptosis initiation of neurons in both age groups. Stress-protected action of alpha-tocoferoli acetate was more significantly in young mice compared to old ones.

[Ontogenetic peculiarities of regulation of apoptosis in hypothalamic neurosecretory cells in thf-knockout mice].

Tumor necrosis factor (TNF) participates in regulation of many processes including carcinogenesis and apoptosis. However, at present, there are practically absent the works on peculiarities of regulation of apoptosis in tnf-knockout (tnf-/-) mice. These mice develop without morphological abnormalities, but they seem to have disturbances of many biological processes, such as inflammation, programmed cell death, etc.