Influence of initial platinum-based chemotherapy on levels of He-4 protein and VEGF-A in primary tumors and metastases from ovarian cancer

Introduction. Recently, the he-4 protein has received great attention due to its diagnostic and prognostic abilities in epithelial ovarian cancer. In addition to its diagnostic value, this protein is involved in the pathogenesis of ovarian cancer. Another significant pathogenetic factor is the vascular endothelial growth factor (vegf) which plays a key role in neoangiogenesis. The purpose of the study focused on the analysis of he-4 and vegf-a levels in tissues of ovarian cancer, in healthy contralateral ovaries and in common metastatic tumors in the omentum and peritoneum to determine the place and role of these tumor markers at the stages of carcinogenesis. Material and methods. The study was performed using the abovementioned tissues of 93 patients with t2-3nхm0-1 ovarian cancer. 51 patients underwent surgery followed by chemotherapy. 42 patients received initial neoadjuvant chemotherapy followed by surgery and adjuvant cytostatic therapy. Tissue samples from 17 patients with benign diseases were used as the control for determining the reference values for he-4 and vegf-a. A comparison was made between groups of patients with and without neoadjuvant therapy, as well as in groups of patients depending on the effectiveness of cytostatic treatment. Results. The levels of he-4 in primary and metastatic tissues affected and not affected by cancer were initially elevated in patients with ovarian cancer. The chemotherapy effectiveness directly correlated with the level of he-4 reduction, which did not change or increased in tumors resistant to medical treatment. The level of vegf-a significantly differed in cancer and non-cancer tissues, which indicated its significant pathogenetic effect not “before”, but at the stages of morphological malignization. The dynamics of vegf-a decrease in this study did not depend on the chemotherapy effect. Conclusion. The he-4 marker is a pathognomonic factor in the development of ovarian cancer, preceding morphological signs of malignancy and reflecting the effectiveness of chemotherapy, while vegf-a is most likely a consequence of the cancer development.

Clinical and genetic parallels in congenital brain lesions without epilepsy

Background. The problem of preventing the development of gross congenital brain lesions and their successful treatment is more than relevant now. It is known that approximately in every third case of the development of congenital cerebral palsy (CP), it is impossible to identify the main pathogenetic factor. This determines the activity of the search for gene mechanisms for the formation of this phenotype. G. McMichael et al. were among the first to identify the most relevant directions of the influence of genes on the formation of the CP phenotype.Objective: to study the influence of gene determinants on the formation of the phenotype of CP, which is not accompanied by epilepsy.Materials and methods. Gene abnormalities in 18 patients with CP were divided into groups of determinable physiological processes. Genetic mutations were confirmed by next generation sequencing (NGS) and Sanger trio methods. For the study, samples of the patients' venous blood were taken.Results and discussion. The analysis showed that genes from different groups by determinants are to varying degrees associated with the formation of the CP phenotype. The “map of determinants” in the pathogenesis of CP is specific. The pathogenesis involves genetically determined disorders of cell division and neuroontogenesis (neuronal migration, sprouting, myelination, partly apoptosis), cell metabolism, including those whose disturbance leads to the formation of storage diseases, transmembrane transport, the exchange of neurotransmitters and the functioning of synapses, the formation of and the functioning of the cytoskeleton, as well as the regulation of immunity and oncogenesis. Malformations of the brain are more often associated with determinants of the regulation of the formation and functioning of the cytoskeleton, neuroontogenesis, as well as the processes of cell division (chromatin modification, transcription, replication). The pathogenesis of congenital cerebral palsy does not involve (according to our data) the determinants of canalopathy, energy supply of the cell, intracellular synthesis with the Golgi complex, and ribosomal synthesis.Conclusions. Genetically determined CP is a universal phenotype that implements the multidirectional effect of the genome. The influence of the genome does not apply to the energy supply of the cell, ribosomal synthesis and the functioning of the Golgi complex. In the absence of epilepsy in the phenotype, there is no influence of the genes of canalopathies.

Hyperoxia Leads to Transient Endocrine Alterations in the Neonatal Rat During Postnatal Development

Introduction: High oxygen concentrations have been identified as one factor contributing to the pathogenesis of the retinopathia of prematurity, chronic lung disease of the preterm infant and preterm brain injury. Preterm infants also show short- and long-term alterations of the endocrine system. If hyperoxia is one pathogenetic factor has not been investigated yet. With regard to the high prevalence of neurodevelopmental impairments in preterm infants, the hypothalamus-pituitary-thyroid (HPT) axis, the hypothalamus-pituitary-adrenal (HPA) axis and the hypothalamus-pituitary-somatotropic (HPS) axis are of special interest due to their important role in neurodevelopment.Objective: The aim of this study was to investigate the effect of hyperoxia on the endocrine system in the neonatal rat by analyzing the activities of the HPT, HPA and HPS axes, respectively.Methods: Three-days old Wistar rats were exposed to hyperoxia (oxygen 80%, 48 h). On postnatal day 5 (P5) and P11, transcript levels of thyroid-stimulating hormone (TSH), proopiomelanocortin and growth hormone (GH) were analyzed in pituitary sections by in situ hybridization. Serologic quantification of TSH and thyroxine (T4), adrenocorticotropic hormone and GH were performed by Multiplex analysis and Enzyme-linked Immunosorbent Assay.Results: At P5, significantly lower GH levels were observed in pituitaries (mRNA) and in sera of rats exposed to hyperoxia. Serum TSH was significantly elevated without changes in T4.Conclusion: This is the first study demonstrating transient endocrine alterations following hyperoxia in the neonatal rat making oxygen a possible contributor to the pathogenesis of endocrine alterations seen in preterm infants. Considering the detrimental multi-organ effects of hyperoxia on the immature organism, a rational use of therapeutic oxygen in the treatrnent of preterm infants is of utmost importance.

Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia—disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects ( p = 0.0041 ), and this may be due to the lower folate level in patients ( p = 0.0072 ). In patients, negative correlation was found between the level of Hcy both with the level of folate ( ρ = − 0.38 , p = 0.0063 ) and with the level of B12 ( ρ = − 0.36 , p = 0.0082 ). At the same time, patients showed higher levels of oxidative modification of serum proteins ( p = 0.00046 ) and lower catalase (CAT) activity ( p = 0.014 ). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 μmol/l, n = 42 ) compared with other patients ( n = 8 ), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019 ), lack of spontaneity and flow in conversation (N6, p = 0.022 ), stereotyped thinking (N7, p = 0.013 ), and motor retardation (G7, p = 0.050 ). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

CHARACTERISTICS OF GUT MICROBIOTA IN AUTOIMMUNE DISEASES OF THE THYROID GLAND AND THE METHODS OF ITS CORRECTION

Gut microbiota is considered as a pathogenetic factor of various diseases nowadays. The patients with autoimmune diseases are known to suffer from dysbiosis. There are studies in the modern literature that demonstrate changes in the composition of the gut microbiota in case of thyroid dysfunction. This review examines a contemporary view of the gut microbiota, its role in the development of autoimmune diseases. We investigated the interaction between the thyroid gland and the gut microbiota, its species composition in hypo- and hyperthyroidism. Possible methods of correction, including the use of pre- and probiotics and transplantation of fecal microbiota have been demonstrated.

Exosome-associated mitochondrial DNA from patients with ME/CFS stimulates human cultured microglia to release IL-1β

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise and cognitive problems. The pathogenesis of ME/CFS is presently unknown and serum levels of potential biomarkers have been inconsistent. Here we show that serum mitochondrial DNA (mtDNA), associated with exosomes, is increased in ME/CFS only after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant release of IL-1β from cultured human microglia. These results provide evidence for a potential novel pathogenetic factor and target for treatment of ME/CFS.

Exosome-associated Mitochondrial DNA is Elevated in Patients with ME/CFS and Stimulates Human Cultured Microglia to Secrete IL-1β

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise and cognitive problems. The pathogenesis of ME/CFS is presently unknown and serum levels of potential biomarkers have been inconsistent. Methods: Exosomes were purified from serum obtained from patients with ME/CFS before and after exercise and their content of mitochondrial DNA (mtDNA) was determined by quantitative PCR. Exosomes from both patients and controls were incubated with cultured human microglia and release of interleukin-1beta (IL-1β) was measured by ELISA.Results: Here we show that serum mtDNA, associated with exosomes, is increased in ME/CFS after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant secretion of IL-1β from cultured human microglia. Conclusion: These results provide evidence for a potential novel pathogenetic factor and target for treatment of ME/CFS.

The role of acute respiratory infections in the pathogenesis of distal limb infections in cattle

Acute respiratory diseases of infectious etiology of cattle occupy the second place in the nosological picture after diseases of the digestive system and cause huge economic damage, which in the Russian Federation is estimated at several billion rubles annually. Very often, respiratory pathology in highly productive cows is associated with infections of the distal extremities, primarily with necrobacteriosis, streptococcosis and staphylococcosis, which cause significant economic damage by reducing the productivity of animals. An important pathogenetic factor affecting the development of diseases of the distal extremities in cattle (cattle) are infections of the respiratory tract. According to our long-term observations, all farms in which outbreaks of necrobacteriosis were recorded were unfavorable for respiratory infections of cattle, such as infectious rhinotracheitis (IRT), viral diarrhea (VD), parainfluenza type 3 (PG-3), respiratory syncytial infection (RSI), pasteurellosis, chlamydia, salmonellosis and others.