RESUMEN
The review describes the involvement of various hyaluronic acid receptors, including CD44, RHAMM, HARE, TLR, LYVE-1, in maintaining normal homeostasis and aging, as well as in the development of age-associated inflammatory processes (inflamaging) and malignant tumors. The association of CD44 receptor activation with immune cells and the development of coronary heart disease has been shown. In addition, a link between the CD44 receptor and osteoarthritis has been shown, via TLR2 and TLR4. The oncogenic potential of RHAMM in relation to breast, prostate, leukemia, pancreas, lung and glioblastoma cancers has been described, with the strongest expression observed in metastatic tumors. In vivo and in vitro experiments, it was found that fragments of hyaluronic acid with a length of 4 to 25 disaccharides can contribute to the proliferation of lymphatic endothelial cells and lymphangiogenesis. Thus, hyaluronic acid receptors play an important role in the aging process through the regulation of inflamaging and in the development of malignant neoplasms.
Asunto(s)
Envejecimiento , Receptores de Hialuranos , Neoplasias , Humanos , Envejecimiento/metabolismo , Envejecimiento/fisiología , Receptores de Hialuranos/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Ácido Hialurónico/metabolismoRESUMEN
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.
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Neoplasias Pulmonares , Pulmón , Humanos , Neoplasias Pulmonares/diagnóstico , Biomarcadores de TumorRESUMEN
The literature review is devoted to the role of kisspeptins in aging. There are data about the involvement of kisspeptins in the development of menopause and ovarian aging, as well as metabolic syndrome. In addition, the role of kisspeptins in the development of age-related diseases such as diabetes mellitus, coronary heart disease, and Alzheimer's disease is described. Involvement of kisspeptins and kisspeptin receptors in the development of malignant neoplasms are postulated. Evidence of the antimetastatic properties of the kisspeptin protein, as well as the possibility of using it as a tumor marker, is presented.
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Kisspeptinas , Ovario , Femenino , Humanos , Kisspeptinas/metabolismo , Menopausia , Ovario/metabolismo , ReproducciónRESUMEN
Determination the activity of the genes of sirtuin-1, hyaluronidase, TGF-ß cytokine, calreticulin in the process of replicative aging of human fibroblasts in vitro and the effect of hyaluronan preparations with gold nanoparticles on the activity of replicative cell aging. Compared the expression of proteins of the studied genes using specific markers at 7 and 14 passages of cultivation of fibroblasts isolated from human skin, without drugs and in the presence of drugs in the growth medium. This work shows a decrease in the activity of the sirtuin 1 gene and an increase in the expression of hyaluronidase in the process of replicative aging of human fibroblasts. Found a means of slowing down replicative aging by activating the SIRT-1 gene and reducing the activity of hyaluronidase in action in the growth medium of hyaluronan preparations with gold nanoparticles. The discussed variants of cell transitions to the pathological state, caused by replicative aging and the mechanisms of slowing down the replicative aging of human fibroblasts.
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Ácido Hialurónico , Nanopartículas del Metal , Humanos , Ácido Hialurónico/farmacología , Oro/farmacología , Oro/metabolismo , Hialuronoglucosaminidasa/metabolismo , Hialuronoglucosaminidasa/farmacología , Envejecimiento/genética , Fibroblastos/metabolismo , Senescencia Celular , Citocinas/metabolismo , Células CultivadasRESUMEN
Most patients over 50 years of age are diagnosed with diseases of the dentoalveolar apparatus, in particular, bone tissue disorders, which leads to a decrease in the survival rate of implants. Identification of the causes, as well as the development of a methodology for predicting survival by minimally invasive methods, is relevant. The aim of the study was to study the markers of tight junctions in the buccal epithelium (BE) in people of different ages. BE scrapings were taken before and after implantation in patients divided into 5 age groups, from young to centenarians. Immunocytochemical method was used to study markers for tight junction proteins - claudin-1, -7 and 10. It has been shown that with age there is a decrease in the intensity of expression of adhesion molecules, in particular claudin -1, -7 and -10 in the mucous membranes, the minimum values were recorded in the group of centenarians. The study found that after dental implantation, there was a decrease in the expression of claudin-1 and -10 and an increase in the expression of claudin-7. Changes in the expression of claudins may indicate the development of a pathological process in the body, including the success of implantation, especially in people of older age groups.
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Claudinas , Uniones Estrechas , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Claudina-1/metabolismo , Claudinas/metabolismo , Uniones Estrechas/metabolismo , Epitelio , Biomarcadores/metabolismoRESUMEN
The aim of the work was to study the expression of sirtuins 1 and 6 and kisspeptin in human ovarian tissue taken in different periods of ontogenesis: from the formation of a pool of follicles in the antenatal period to the extinction of ovarian function in postmenopausal women. It was revealed that sirtuins are expressed in human ovary tissue in all age groups. The maximum expression level of SIRT1 in ovarian tissue was observed during intrauterine development and during the perimenopause, SIRT6 during the reproductive period and perimenopause. The participation of SIRT1 in prenatal selection of oocytes in human fetuses was shown, since it was in this group that increased expression of this marker was revealed. The expression level of the kisspeptin marker increases with the formation of the ovaries and the inclusion of reproductive function; the peak of expression is observed in the period before the onset of menopause. The study conducted to identify the expression of these proteins in the human ovary expands the understanding of the regulation of the ovarian follicular reserve and reproductive aging.
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Ovario , Sirtuinas , Envejecimiento , Femenino , Humanos , Kisspeptinas , Menopausia , Embarazo , Sirtuina 1RESUMEN
To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular-cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been practically studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3rd and 14th passages, corresponding to «young¼ and «old¼ cultures, were used to simulate cellular senescence. Results. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16INK4a compared to «young cultures¼ both in the control group and in the group with DCMP. It was also found that the expression of p16INK4a in cultures taken from patients with pathology was 2 times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in a «young¼ culture compared with the norm, 3,2 times. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.
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Cardiomiopatía Dilatada , Miocitos Cardíacos , Envejecimiento , Apoptosis , Humanos , MiocardioRESUMEN
It was verified new molecular targets of geroprotective activity of AEDG (epitalon) and KE (vilon) peptides by the method of confocal laser scanning microscopy. It was shown that the MitoTracker Red mitochondries staining decreased and L7A ribosomal protein synthesis compensatory increased during pineal and thymic cell senescence in vitro. AEDG peptide increases in 1,5 times the square of MitoTracker Red mitochondries staining and decreases on 22% the expression of ribosomal protein L7A in cultures of human pineal gland cells during its senescence. KE peptide increases in 1,5 times the square of MitoTracker Red mitochondries staining and decreases on 15% the expression of ribosomal protein L7A in cultures of human thymic cells during its senescence. The square of MitoTracker Red mitochondries staining decreases and the expression of L7A ribosomal protein compensatory increases during pineal gland and thymic cells senescence. We can suppose that AEDG and KE peptides have a tissue-specific effect that normalizes the functions of mitochondria and ribosomes of pinealocytes and thymocytes.
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Glándula Pineal , Senescencia Celular , Colorantes , Humanos , Péptidos , Ribosomas , TimoRESUMEN
Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117+ cells into mature CD28+T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28+, CD4+, CD8+T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28+T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.
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Diferenciación Celular/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/fisiología , Hormonas del Timo/farmacología , Antígenos CD28/genética , Antígenos CD28/metabolismo , COVID-19/inmunología , COVID-19/patología , Diferenciación Celular/genética , Células Cultivadas , Sangre Fetal/citología , Regulación de la Expresión Génica/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Humanos , Receptores de Hialuranos/genética , Receptores de Hialuranos/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , SARS-CoV-2/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T/fisiología , Hormonas del Timo/fisiologíaRESUMEN
PURPOSE: Kisspeptins regulate the trophoblast invasion. The disturbance of this process might lead to the development of preeclampsia (PE). Diabetes mellitus (DM) is associated with the high rate of this complication. The main hypothesis was to investigate the placental protein expression of kisspeptin-1 (KISS1) and its receptor (KISS1R) in diabetic, preeclamptic, and healthy pregnancies. METHODS: Placentae (n = 65) were divided into the following groups: the control group (n = 20), either PE or non-PE type-1 diabetes mellitus (T1DM) (n = 10), either PE or non-PE type-2 diabetes mellitus (T2DM) (n = 10), either PE or non-PE gestational diabetes mellitus (GDM) (n = 10) and preeclampsia without diabetes (PE) (n = 15). Immunohistochemistry analysis was used for demonstrating the presence and location of KISS1/KISS1R in placental tissue and to measure the area of immunopositive expression. Correlation analyses were performed to detect the links between protein expression of these biomarkers and the main obstetric outcomes. RESULTS: The highest placental protein expressions of KISS1 were detected in the PE (35.4%) and GDM (33.2%) groups. In case of DM, levels of KISS1 expression depended on the presence of PE and were higher compared with DM no PE and control groups: (30.6%) in T1DM + PE and (30.1%) in T2DM + PE group. The lowest expression was detected in the control group (14.1%). The expression of KISS1R was higher in DM and PE compared to the control group. We detected the strong direct link between PE and placental expression of KISS1 (r = 0.81) and KISS1R (r = 0.56), and inverse correlation link between KISS1 and preterm birth weight (r = - 0.73). The low correlation links were found between KISS1 and IUGR (r = 0.29), and preterm birth (r = 0.24). The same trend was detected for KISS1R. We did not find any significant correlations between placental expressions of KISS/KISS1R and placental weight or HbA1c levels. CONCLUSION: Increased expression levels of KISS1 and KISS1R in case of diabetes mellitus may play a role in the altered placentation process and lead to the development of preeclampsia.
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Diabetes Gestacional/genética , Kisspeptinas/metabolismo , Preeclampsia/genética , Receptores de Kisspeptina-1/metabolismo , Adulto , Estudios de Cohortes , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
The article presents the results of studies of the expression hormones-kisspeptins and their receptors in human ovarian tissues during ontogenesis of this organ. Kisspeptins regulate the hypothalamic-pituitary-gonadal axis, the most important function of which is to launch the mechanism of puberty. Verification of kisspeptins and their receptors in ovarian tissue, suggests that they promote ovulation, as well as controls the expression of matrix metalloproteinases involved in tissue remodeling. The KISS1/KISS1R system begins be active in the period of prenatal development, so that already at week 22 a positive reaction with antibodies to kisspeptin was recorded in the ovarian tissue. It has been established that, at reproductive age, the expression of kisspeptins remains at a consistently high level, whereas during menopause, the expression of kisspeptins in the ovaries has its peak, which may be due to a compensatory mechanism for reducing the synthesis of ovarian estrogens. In postmenopausal period defined minimum values. Further studies of the metabolism of kisspeptins during menopause will contribute to the expansion of knowledge about their mechanism and the possibility of using them as targeted therapeutic agents.
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Envejecimiento , Kisspeptinas , Ovario , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Kisspeptinas/metabolismo , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Receptores de Kisspeptina-1/metabolismoRESUMEN
We compared the expression of signal molecules in the culture of human endothelial cells under normal conditions and in atherosclerosis and restenosis. Expression of connexin-37 and sirtuin-1 in atherosclerosis and restenosis surpassed the normal by 2 and 5 times, respectively, and expression of endothelin-1 3-fold surpassed the normal. In restenosis, changes in the expression connexin-37 and endothelin-1 became more pronounced in comparison with atherosclerosis. Connexin-37 and endothelin-1 can serve as predictive markers for prognosis of post-stenting complications in patients with atherosclerosis.
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Aterosclerosis/metabolismo , Reestenosis Coronaria/metabolismo , Células Endoteliales/metabolismo , Células Cultivadas , Conexinas/metabolismo , Endotelina-1/metabolismo , HumanosRESUMEN
Extrapineal and pineal melatonin is the marker of the aging rate of organism making it possible to characterize functional condition of the neuro-immuno-endocrine system. In this article we have used the new method for non-invasive diagnostics of melatonin expression in buccal epithelium and determination of the main melatonin metabolite 6-hydroxymelatonin sulfate (6-HMS) in urine of elderly people. Normal, impaired and enhanced melatonin expression was documented in 20.5%, 43.2% and 36.30% of the patients respectively. Such comprehensive melatonin and 6-COMT studies can be recommended for elderly patients with oncological, neurodegenerative, cardiovascular diseases, and ageing macular dystrophy. Moreover, melatonin expression analysis in buccal cells can be used for integral investigation of biorhythms in elderly people.
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Envejecimiento/metabolismo , Enfermedades Cardiovasculares/metabolismo , Degeneración Macular/metabolismo , Melatonina , Mucosa Bucal/metabolismo , Neoplasias/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Anciano , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Melatonina/análogos & derivados , Melatonina/análisis , Melatonina/metabolismo , Reproducibilidad de los Resultados , Urinálisis/métodosRESUMEN
Skin aging is one of the topical issues in modern gerontocosmetology. Application of cosmetic products with short peptides is a promising measure for retardation of skin aging. This research is aimed at investigation of KE (Lys-Glu, Vilon) dipeptide influence on the expression of markers of aging in human skin fibroblasts in vitro. Collagen type I and sirtuin-6 expression in «young¼ and «old¼ skin cell fibroblasts cultures was studied using immunofluorescence confocal microscopy method. The areas of expression of collagen type I and sirtuin-6 are known to decrease in skin fibroblasts with aging by 3,5 and 3,6 times accordingly. KE dipeptide increases collagen type I expression area in «old¼ skin fibroblasts cultures by 83%. KE dipeptide increases expression area of sirtuin-6 in «young¼ and «old¼ skin fibroblasts cultures by 1,6 and 2,6 times correspondingly. Thus, KE dipeptide promotes functional activity of skin fibroblasts and inhibits their aging.
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Senescencia Celular/efectos de los fármacos , Colágeno Tipo I/metabolismo , Dipéptidos/farmacología , Fibroblastos/efectos de los fármacos , Ozono/uso terapéutico , Sustancias Protectoras/farmacología , Sirtuinas/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Anciano , Células Cultivadas , Terapia Combinada/métodos , Fibroblastos/fisiología , Humanos , Microscopía Confocal/métodos , Microscopía Fluorescente/métodosRESUMEN
The effect peptides KE, KED, AED and AEDG on proliferation (Ki-67), regeneration and aging (CD98hc), apoptosis (caspase-3), and extracellular matrix remodeling (MMP-9) in skin fibroblasts during their aging in culture were studied by immunofluorescent confocal microscopy. All studied peptides inhibited MMP-9 synthesis that increases during aging of skin fibroblasts and enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging. Peptides AED and AEDG suppressed caspase-dependent apoptosis that increases during aging of cell cultures.
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Fibroblastos/fisiología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Senescencia Celular , Dipéptidos/farmacología , Fibroblastos/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Oligopéptidos/farmacología , Ratas WistarRESUMEN
Peptide KED (Lys-Glu-Asp) has vasoprotective effects and is effective substance in treatment of of atherosclerosis and other cardio-vascular disorders in elderly people. One of the probable mechanisms of biological activity of this peptide is epigenetic genes regulation. These genes can coding proteins, which are markers of endothelium functional activity. The goal of investigation was to study the KED peptide effect on signal molecules expression in normal, atherosclerotic and restenotic endothelium in vitro. It was shown, that KED peptide has normalized endothelin-1 expression, which increased during atherosclerosis and restenosis. KED peptide also restorates cells interactions by connexin expression. Geroprotective effect of KED peptide is realized by increasing of sirtuin1 expression, which has took part in DNA reparation.