[Modern approaches to studying the molecular mechanisms of lung functioning in normal and pathological conditions]. / Sovremennye podkhody k izucheniyu molekulyarnykh mekhanizmov funktsionirovaniya legkikh v norme i pri patologii.

Problems with breathing and lung function are caused by the development of various lung diseases associated with lifestyle, harmful environmental factors and genetic predisposition. Knowledge of the molecular mechanisms of the development of the pathological process will allow on time identification of the disease or the development of targeted therapy. The article provides an overview of modern methods that make it possible to most accurately reproduce the structural, functional and mechanical properties of the lung (organ-on-a-chip), to perform non-invasive molecular studies of biomarkers of bronchopulmonary pathology using saliva diagnostics, as well as using DNA and RNA aptamers, verify tumor markers in biological samples of human tissue. Analysis of alterations in the pattern of protein glycosylation using glycodiagnostic methods makes it possible to detect lung cancer in the early stages.

[Repair stimulator alpha-glutamyl-tryptophan in the complex therapy of chronic atrophic gastritis: results of histological examination]. / Stimulyator reparatsii al'fa-glutamil-triptofan v kompleksnoi terapii khronicheskogo atroficheskogo gastrita: rezul'taty gistologicheskogo issledovaniya.

OBJECTIVE: To study the effect of the repair stimulator alpha-glutamyl-tryptophan on the morphological characteristics of the gastric mucosa and the expression of CXCL-12 and CDX-2 in chronic atrophic gastritis associated with Helicobacter pylori. MATERIAL AND METHODS: Biopsy samples of 116 patients with a verified diagnosis of chronic atrophic gastritis associated with Helicobacter pylori were analyzed in a multicenter double-blind randomized placebo-controlled study. During the morphological study, the parameters characterizing the process of atrophy were evaluated: the number of glands per 1 mm2 of the gastric mucosa, the depth of the gastric mucosa glands, the number of parietal cells per 100 epithelial cells of the gastric mucosa, and the presence of signs of intestinal metaplasia. Primary antibodies Anti-CXCL-12 (MA5-23759) and Anti-CDX-2 (EP25) were used to set up immunohistochemical reactions to verify the expression of CXCL-12 and CDX-2. RESULTS: In patients taking the studied drug, a statistically significant increase in the number of glands per 1 mm2 of the gastric mucosa was revealed when compared with the initial screening indicators by 26.1% (p=0.028) and with the placebo group (p=0.026), a tendency to decrease the signs of intestinal metaplasia was determined. There was a statistically significant increase in the expression in the relative area of CXCL-12 expression in patients taking placebo when compared with the parameters of the initial data (p=0.045) and the absence of statistically significant changes in the main group. A statistically significant increase in the relative area of the CDX-2 expression was revealed in the group taking alpha-glutamyl-tryptophan in comparison with the baseline data (p=0.015), no statistically significant dynamics of this indicator was found in the placebo group. CONCLUSION: A statistically significant positive effect of the study drug on regenerative mechanisms leading to stabilization and/or improvement of the histological picture in the atrophic area of the gastric mucosa was found in comparison with the control of the initial state and with placebo. The results of an immunohistochemical study to increase CDX-2 expression while taking the study drug can also be regarded as an indicator of improvement in reparative processes.

[Heart damage in the combined types of systemic amyloidosis]. / Porazhenie serdtsa pri sochetannykh formakh sistemnogo amiloidoza.

The cardiovascular system is a common target of systemic amyloidosis (SA); amyloid light chain (AL) cardiac amyloidosis (AL-CA), the wild-type transthyretin (ATTRwt-CA), and mutant-type transthyretin (ATTRmt-CA) are the most studied types of SA. The literature describes only single cases of two types of SA in the same patient. OBJECTIVE: To identify and determine the clinical and morphological characteristics of combined types of SA in patients with biventricular chronic heart failure (CHF). MATERIAL AND METHODS: Eighty autopsy protocols for biventricular CHF deaths were retrospectively analyzed. Immunohistochemistry and confocal laser scanning microscopy (CLCM) with antibodies to amyloid A (AA), serum amyloid-P (SAP), prealbumin, and immunoglobulin kappa (κ) and lambda (λ) light chains were performed. RESULTS: The myocardium showed a combination of different types of SA in 6 (7.5%) cases, including Alλ-CA+ATTR-CA, ALκ-CA+ATTR-CA, and AA-CA+ATTR-CA in 4, 1, and 1 cases, respectively. Macroscopically, the heart mass averaged 470±20 g; the thickness of the left and right ventricular myocardium was 1.5±0.2 and 0.4±0.1 cm, respectively; the interventricular septum averaged 1.2±0.2 cm; and the cardiac index was 0.008. The myocardium was dense, dark red with diffuse layers of whitish dense fibrous connective tissue; the heart cavities were enlarged. Microscopically, in 25% of cases, all heart parts had ALλ-CA that was characterized by massive amyloid deposits localized predominantly in the intramyocardial vessel wall, intermuscular connective tissue, and perivascularly. The myocardium also displayed small amyloid deposits of ALλ-CA and ATTR-CA in the intermuscular connective tissue and intramyocardial vessel wall. Amyloid deposits were located in different parts of the myocardium; there were also areas of co-localization of ALλ-CA+ATTR-CA. CONCLUSION: The combined types of SA occurred under the guise of coronary heart disease and the dilated cardiomyopathy phenotype. The combined amyloid AL-CA and ATTR-CA was generally localized in the interstitium and myocardial vessels. There were also small areas of co-localization of amyloid deposits, which were found mainly in the intramyocardial vessels.

[Molecular biological markers for proliferation, apoptosis, and angiogenesis in diffuse toxic goiter]. / Molekuliarno-biologicheskie markery proliferatsii, apoptoza i angiogeneza pri diffuznom toksicheskom zobe.

The pathogenesis of diffuse toxic goiter has not yet been fully understood. The literature increasing commonly focusses on the issues related to the processes occurring in the thyroid gland itself: proliferation, apoptosis, and angiogenesis. AIM: to investigate clinical and laboratory parameters, as well as the expression of Ki-67, Bcl-2, Bax, Fas-L, CD34, VEGF, and FGF proteins in various postoperative outcomes of patients operated on for diffuse toxic goiter. SUBJECTS AND METHODS: The investigation enrolled 24 women who had undergone surgery using the technique described by E.S. Drachinskaya. Immunohistochemical tests were carried out according to the standard protocol. The expression of Ki-67, Bcl-2, Bax, Fas-L, CD 34, VEGF, angiopoietin, and FGF proteins was determined. RESULTS: The patients with postoperative thyrotoxicosis were ascertained to have a significantly greater expression of anti-apoptotic protein Bcl-2, proliferation marker Ki-67, vascular factors (FGF, VEGF), and CD 34. CONCLUSION: The relative expression area of the anti-apoptotic protein Bcl-2 of more than 2.19 or the proliferation protein Ki-67 of more than 1.059 was found to predict the development of postoperative thyrotoxicosis with an accuracy of higher than 85%.

Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.

The expression of cytokine LIF (leukemia inhibiting factor) in the endometrium of women of young reproductive age with non-developing pregnancy of unknown genesis is higher than in older women and women with infection-related miscarriages by 1.26 and 1.43 times, respectively. The expression of angiogenesis marker CD34 in the endometrium of young women with non-developing pregnancy of unknown origin is 1.59 times higher and in case of endometrial inflammation 1.31 times higher than in women of the older reproductive age with the same disease. Correlation between the endometrial expression of LIF and CD34 is detected in women of the younger reproductive age with non-developing pregnancy of unknown etiology. The expression of LIF and CD34 can be used for endometrial function evaluation in women of different age with first trimester non-developing pregnancy.

[Expression of matrix metalloproteinases and their inhibitors in the internal carotid artery wall in pathological tortuosity]. / Ekspressiya matriksnykh metalloproteinaz i ikh ingibitorov v stenke vnutrennei sonnoi arterii pri patologicheskoi izvitosti.

UNLABELLED: The principal morphological sign of fibromuscular dysplasia in pathological tortuosity (PT) of the internal carotid artery (ICA) is the fragmentation of elastic fibers that are degraded by matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). Nevertheless, the role of MMPs and their inhibitors in the pathogenesis of ICA PT remains completely unexplored. AIM: to investigate the expression of elastin-degrading MMPs and their inhibitors in the wall of the ICA in PT by immunohistochemistry and confocal laser scanning microscopy. METHODS: Immunohistochemical examination was made using antibodies to MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2. MMP-9 and TIMP-1 levels were determined by confocal laser scanning microscopy. RESULTS: Immunohistochemical examination revealed a statistically significant predominance of high concentrations of MMP-2 and MMP-9 and a low level of their inhibitor TIMP-1 in ICA PT, while simultaneous obvious accumulation of both markers was most often identified in the control group (p<0.05). Analysis of MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios showed the prevalence of the simultaneously high expression of both proteins in ICA PT and in the control group too. The similar data were also obtained by confocal microscopy: the control group showed elevated MMP-9 and TIMP-1 expressions and the ICA PT control displayed a high proteinase and low inhibitor levels (p<0.05). CONCLUSION: Elastic fiber fragmentation in ICA PT is due to imbalance between MMPs and their inhibitors; namely, the prevalence of MMP-2 and MMP-9 over their inhibitor TIMP-1, which leads to the degradation of extracellular matrix components, primarily elastin.

[The structure of the internal carotid artery wall in pathological tortuosity].

OBJECTIVE: to study a change in the content of main components of the internal carotid artery (ICA) wall in pathological tortuosity (PT) resulting from fibromuscular dysplasia, using immunohistochemistry and confocal laser scanning microscopy. MATERIAL AND METHODS: Immunohistochemical (IHC) analysis using antibodies to elastin, collagen types I and III, and smooth muscle actin was made. The levels of elastin and matrix metalloproteinase 9 (MMP-9) were determined by confocal laser scanning microscopy. The relative area of expression and the area of co-location of these markers were measured. RESULTS: IHC examination of the expression of elastin revealed that the patients with PT of ICA had its higher content than the controls, but they were observed to have fiber fragmentation. Comparison of collagen types I and III expressions showed no significant differences between the groups. The found significantly lower smooth muscle actin expression in the patients with PT of ICA than in the controls was suggestive of the decreased levels of smooth muscle cells. Confocal microscopy analysis showed high elastin and low MMP-9 expressions in the control group and, on the contrary, low elastin and high proteinase levels in the PT group (р<0.05). CONCLUSION: One of the causes of PT is impairment in vascular elastic properties due to the destruction of elastic fibers and to their fragmentation, as well as to the decreased count of smooth muscle cells, which in turn causes enhanced MMP-9 activity and tissue matrix degradation.