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Vol 20, No 3 (2022)
- Year: 2022
- Articles: 9
- URL: https://journals.eco-vector.com/1728-2918/issue/view/5815
- DOI: https://doi.org/10.29296/молмед.v20i3
Articles
Sarcoidosis: molecular markers and targets for targeted diagnosis and therapy
Abstract
The review is devoted to the analysis of modern ideas about the molecular mechanisms of the pathogenesis of sarcoidosis, it describes the signaling molecules involved in the development of sarcoidosis, which can be biomarkers and targets for optimizing personalized diagnosis and targeted therapy of the disease. The aim of the study was to consider the possible mechanisms of development of granuloma and fibrosis of the lung tissue in this pathology and to characterize the molecular markers of sarcoidosis. Material and methods: the analysis and systematization of scientific literature over the past 5 years was carried out in the PubMed, Scopus and Google Scholar databases. Results. The review focuses on various subpopulations of lymphocytes, as well as angiogenic factors (VEGF and HIF-1a) and molecules associated with the development of inflammation (TNF-a, IFN type I, Janus kinase, COX-2). The possible epigenetic regulation of the processes occurring in sarcoidosis with the help of miRNAs is considered. The possibility of using the analysis of single nucleotide polymorphisms of genes to identify a risk group for the development of sarcoidosis, as well as an unfavorable prognosis for its course, is discussed.
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The role of the intestinal microbiota in the pathogenesis of bronchial asthma
Abstract
It is currently being discussed that the microbiota of the gastrointestinal tract and its metabolites affect the course of bronchial asthma (BA). The purpose to summarize the available data on the role of the intestinal microbiota in the pathogenesis of ВА. Material and methods. A analysis of the main foreign and domestic sources on PubMed / Medline, RSCI / elibrary databases over the last 25years has been carried out. Results. In the course of the analysis of published works, the key links in the pathogenesis of ВА and changes arising from disturbance of intestinal microbiota composition (hygienic hypothesis, early prescription of antibacterial drugs) were compared. The results of studies on the role of bacterial overgrowth syndrome in the small intestine are analyzed. The results of studies where microbiota correction by prescribing probiotics and prebiotics resulted in positive effects on the course and prognosis in ВА are presented. Conclusion. A lot of data has been accumulated confirming the significant pathogenetic role of the microbiota. The positive effects of pro-and prebiotics both on the microbial composition of the intestine and on the course and prognosis in ВА allow us to consider the microbiome as a marker and a possible target in ВА therapy. All of the above dictates the need for further research in this area.
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Progastrin-releasing peptide (proGRP) and neuron specific enolase (NSE) in survival prognosis in patients with small cell lung cancer
Abstract
Introduction. Small cell lung cancer (SCLS) is a highly aggressive type of tumor, and various compounds are considered as potential biochemical markers of its prognosis, including neuron-specific enolase (NSE), chromogranin A (CgA), and prograstrin releasing peptide (proGRP). The aim of the study. Analysis of basal serum concentrations of biochemical markers proGRP, NSE, and CgA association with the prognosis of progression-free survival in patients with SCLC. Methods. 62 patients with late-stage SCLC (III-IV) who received treatment using modern chemotherapy schemes was included in our investigation. Progression-free survival was analyzed from the start of the first course of chemotherapy to the detection of progression. ProGRP and NSE detection in blood serum was performed on the automatic biochemical analyzer Cobas e601 (Roche). CgA analysis was performed with ELISA method (Eurodiagnostica). Results. The medians of all studied markers were statistically significantly differentfrom the control. We revealed an association between basal serum levels of proGRP and progression-free survival in patients with SCLC (p=0.0039); while in the group of patients with proGRP levels over 1384pg/ml, the prognosis was less favorable. Survival analysis using NSE levels showed that in the group of patients with SCLC with levels above 72.9 ng/ml, the survival prognosis was less favorable (p=0.015). The simultaneous increase of proGRP and NSE secretion was a prognostically unfavorable factor. Conclusion. ProGRP and NSE can be used as predictors of progression-free survival in patients with advanced SCLC, and high marker levels were associated with an unfavorable prognosis.
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Еffect of tripeptides on growth of organotypic culture of different genesis tissues
Abstract
Tripeptides are physiological products of protein degradation and informational molecules. AED (Ala-Glu-Asp), EDR (Glu-Asp-Arg), EDG (Glu-Asp-Gly) peptides have geroprotective, neuroprotective, reparative and antioxidant properties. The aim of the work is to evaluate the effect of the AED, EDR, EDG peptides on the development of organotypic tissue culture of various genesis in young and old rats. Material and methods. Tissues for organotypic cultivation of mesodermal genesis (testis), ectodermal genesis (cerebral cortex) and entodermalgenesis (bladder) were obtained from young (2-3 months) and old (16-18 months) Wistar rats. Results. AED peptide stimulated cell growth in meso- and endodermal tissues of young and old animals. EDR peptide activated cell proliferation in ecto- and mesodermal tissues of young and old rats. EDG peptide had a stimulating effect on the mesodermal tissue of young rats. Conclusion. Tripeptides, depending on the composition and sequence of their amino acids, have different effects on meso-, ecto- and endodermal genesis tissues obtained from animals of different ages. This indicates the possibility of targeted geroprotective action of AED, EDR, EDG peptides.
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Molecular markers of endometrial carcinoma and associated clinicopathological features
Abstract
Introduction. In 2013 The Cancer Genome Atlas research group divided the molecular aberrations in endometrial cancer into four subtypes: POLE mutations, microsatellite instability, copy-number low and copy-number high. These subtypes have different prognosis and could probably mean different therapeutical options. The aim of the study. To estimate the prevalence of different molecular aberrations and to find out associated clinicopathological features. Methods. The study included 45 samples of endometrial carcinoma. Pathological structure and molecular features of each sample were evaluated. Immunohistochemical testing was used to find out the level of p53 expression. Genetic testing was carried out by PCR for MSI testing and by sequencing POLE exon 9 and exon 13 for point mitations. Results. Nor POLE mutations, nor abnormal p53 expression level were found in studied samples. The prevalence was 22% for MSI tumors. No significant difference in clinicopathological features was found between MSI and MSS tumors except for mitotic index that was higher in MSI tumors. Similarly, MSI tumors were less differentiated but the difference was not statistically significant. Conclusion. POLE mutations and abnormal p53 level are rare in low-grade endometrial carcinomas. Nevertheless, MSI tumors are common in this group and further research of their prognostic significance is important.
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Neuroimmune changes in atopic dermatitis during pregnancy
Abstract
Introduction. An increase in the number of patients with atopic dermatitis (AD) among pregnant women is recorded annually. However, the pathogenesis of AD during pregnancy is not fully understood. Exacerbations of AD during pregnancy require in-depth study, since at the moment there are no uniform recommendations for the treatment and management of such patients. The aim of the study. To study the role of cytokines (IL-31 and IL-33), neuropeptide - substance P (SP) and cortisol in the pathogenesis of AD during pregnancy before and after combined topical treatment. Material and methods. The study included 110patients, including 70 pregnant women with exacerbation of AD, 20 - non-pregnant women with exacerbation of AD, 20 - healthy pregnant women. A group of pregnant women with exacerbation of AD received combined therapy "emollient + topical antipruritic agent" for 30 days. Patients were assessed in dynamics: control of symptoms and severity of AD (SCORAD index), IL-31 and IL-33, SP, cortisol. Statistical processing was carried out using the Statistica 6.0 software package. Results. When assessing the severity of AD, no significant differences were found between the groups. In the group of pregnant women with exacerbation, higher levels of IL-31, IL-33, cortisol, and SP were noted. At the end of a 30-day course of treatment for exacerbation of AD during pregnancy with a combination of "emollient + topical antipruritic agent", a significant change in the SCORAD index, IL-31, IL-33 and cortisol was recorded. Conclusion. Exacerbation of AD during pregnancy is accompanied by more pronounced changes in neuro-immunological parameters (IL-31 and IL-33, SP), as well as in the level of the stress hormone cortisol than in the control groups. The combination "emollient + topical antipruritic agent" in the course of the study showed clinical efficacy in eliminating the skin inflammatory process and contributed to a decrease in neuroimmune parameters.
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Investigation of the metabolite composition of lactic acid bacteria strains on the basis of a probiotic drug
Abstract
Introduction. Lactic acid bacteria synthesize antimicrobial substances of various nature: acids, alcohols, diacetyl, reuterin, hydrogen peroxide, carbon dioxide, etc. The Food and Drug Administration (USA) and the European Food Safety Authority have recognized lactic acid bacteria as safe for human and animal health. In this regard, they can also be of great importance as producers of amino acids, including essential ones. The purpose of the study is to carry out a comparative analysis of the organic and amino acids production by strains of probiotic bacteria. Material and methods. Selected strains of lactic acid bacteria were used: Lactobacillus plantarum IMV B-7344, Lactobacillus casei IMVB-7343, Lactobacillus acidophilus RCAM 01850, Lactococcus lactis subsp. lactis RCAM 02909, Lactococcus lactis subsp. cremoris RCAM 05396, Streptococcus thermophilus RCAM 02910. Analysis of amino acids and organic acids was carried out with capillary electrophoresis "Capel 105" and the program "Multichrom". Results. All the studied strains have a fermentation-type metabolism with formation of lactic, acetic, butyric and caproic acids with a total production level of up to 29.06 g/l. The production of malic and succinic acids by lactobacilli (0.06-0.59 g/l) should be noted, as opposed to lactococci and streptococcus, which do not synthesize these acids even in trace amounts. The content of free amino acids in the submerged cultivation process was 35.88-49.06 g/l, including essential 11.81-21.21 g/l. Significant amounts of leucine and isoleucine (8.63-17.20 g/l), glutamine (9.83-10.60 g/l) and proline (5.42-7.48 g/l) were noted in the culture fluid, with the first two being essential. Conclusion. The data obtained must be taken into account when developing multicomponent probiotics, since these factors largely determine the effectiveness of the impact on pathogenic microorganisms and humans.
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Molecular mechanisms of neuroprotection of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one in experimental traumatic brain injury
Abstract
Introduction. Neuroprotection in traumatic brain injury is a promising area of therapy for cerebral disorders. Neuroprotective effect can be implemented by a action on variety molecular targets, a change in the activity of which leads to the elimination of pathogenetic reactions of secondary brain damage. Such targets can include the ultrastructures of the mitochondria of the cell. The aim of the study. To evaluate possible molecular mechanisms of neuroprotection of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one in the context of changes in mitochondrial function under experimental traumatic brain injury. Material and methods. Traumatic brain injury was simulated in Wistar rats by free-falling of a load (150 g) from a height of 50 cm onto the parietal region of the animal's skull. The tested compound and the reference medication (ethylmethylhydroxypyridine succinate) were administered per os for 7 days after injury. After the specified time, the degree of development of neurological deficiency in animals was determined on the mNSSscale, the activity of enzymes in brain tissue was evaluated: succinate dehydrogenase, citrate synthase, cytochrome c oxidase and aconitase. The change in the concentration of annexin Vwas also evaluated. Results. It was found that the use of the tested compound and the reference significantly reduced the severity of neurological symptoms in rats by 31.6% (p<0.05) and 43.4% (p<0.05), respectively, relative to untreated animals. At the same time, the adminiatrstion of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one led to a more pronounced increase in the activity of the evaluated enzymes than the use of the referent. The concentration of annexin V decreased against the background of the administration of the tested compound and the reference by 18.7% (p <0.05) and 31.8% (p <0.05), respectively, by animals. Conclusion. The study showed that the administration of 3-[(E)-3-(3,5-ditret-butyl-4-hydroxyphenyl)-3-oxoprop-1-enyl]-6-methoxy-chromene-4-one to animals under experimental traumatic brain injury increases the activity of enzymes of cellular metabolism: succinate dehydrogenase, citrate synthase, cytochrome c oxidase and aconitase, which in turn can lead to reduction of apoptosis reactions and development of neuroprotective effect.
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Effect of polypeptide complexes on the development of skin organotypic tissue culture of different age rats
Abstract
Introduction. The creation of peptide bioregulators that contribute to the preservation of the basic physiological functions of the body is an urgent task of modern biology and medicine. The aim of the study was to evaluate the effect of polypeptide complexes (PPCs) isolated from the ovaries, muscles and vessels of calves on the growth of skin cells of young and old rats. Methods. Organotypic cultivation of rat skin tissue was carried out under the action of various PPCs. The growth of skin tissue was calculated by the area index (IP). The expression of proliferation markers (PCNA) and apoptosis (p53) was evaluated by immunocytochemistry. Results. All the studied demonstrated the statistically significantly increased the area index (IP) of skin explants in young rats by 30-49% and in old animals by 20-28%. The expression of p53protein decreased in the skin explants of young and old rats by 20-30% and 17-27%, respectively under the action of PPCs. PCNA protein expression in skin cultures obtained from young and old animals increased by 22-39% and 19-31% respectively after adding PPCs adding. Conclusion. The obtained data create the base for the development of new substances based on the studied PPCs that contribute to the correction of pathology and age-related skin changes.
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