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卷 17, 编号 5 (2019)
- 年: 2019
- 文章: 9
- URL: https://journals.eco-vector.com/1728-2918/issue/view/5758
- DOI: https://doi.org/10.29296/молмед.v17i5
Articles
Rejuvenating manf factor and its functions in normal and pathological conditions
摘要
There are presented data about rejuvenating mesencephalic astrocyte-derived neurotrophic factor (MANF) and its physiological functions. This is a new neurotrophic factor, produced by the mesencephalic astrocytes and it is different from other factors by its activity concerning not only the nervous tissue but other tissues. The MANF main function is a protection of the dopamine neuron endoplasmic reticulum (ER) from the stress and apoptosis. The high concentrations of MANF were detected in the brain cortex, hippocampus, cerebellum. MANF is expressed actively in the synovial tissues, cardiomyocytes, pancreas cells, liver tissue. The MANF provides an increase of the regenerative processes, affecting the immune cells. The MANF ability to modulate the cell regenerative functions and the neuroprotection, and also an increase of the stem cell function, plays a great role in the so-named “rejuvenating” functions of MANF. It was detected, using the method of the heterochronic parabiosis, that the MANF concentration is increased highly in the blood of the old mice by an increase of the neuron quantity in the brain, and also by the improvement of the heart, liver function. MANF can protect the cilia of dopaminergic neurons at the early stage of Parkinson disease, it has the neuroprotective effect in the early stages of the brain damage, produced by the subarachnoidal bleeding in the mice. The MANF protein, possessing many functions, plays the basic role in the processes of the recovery of the neuron functions in both Alzheimer and Parkinson diseases, insults and traumatic damages of the brain. There are data presented about rejuvenating mesencephalic astrocyte-derived neurotrophic factor (MANF) and its physiological functions. This is a new neurotrophic factor, produced by the mesencephalic astrocytes and it is different from other neurotrophic factors by its activity concerning not only the nervous tissue but many other tissues. The MANF main function is a protection of the dopamine neuron endoplasmic reticulum (ER) from the stress and apoptosis development. The relatively high concentrations of MANF were detected in the brain cortex, hippocampus and in the cerebellum Purkinje cells. Moreover, MANF is expressed actively in the synovial tissues by their infiltration with the inflammatory cells, in the cardiomyocytes, pancreas cells, in the B hepatitis liver tissue. The MANF immunomodulating function provides an increase of the regenerative processes, affecting directly the immune cells. The MANF ability to modulate the cell regenerative functions by the synchronous stimulation of the neuroprotection, and also of an increase of the stem cell function, plays a great role in the so-named «rejuvenating» functions of this protein. It was detected, using the method of the heterochronic parabiosis (the creation of the common blood circulation in the young and old animals), that the MANF concentration is increased highly in the blood of the old mice by an increase of the neuron quantity in the brain, (especially in the hippocampus), and also by the improvement of the heart, liver function. MANF can protect the cilia of dopaminergic neurons at the early stage of Parkinson disease, and also it has the neuroprotective effect in the early stages of the brain damage, produced by the subarachnoidal bleeding in the mice. The MANF protein, possessing many functions, plays the basic role in the processes of regeneration, increase and recover of the neuron functions in both Alzheimer and Parkinson diseases, insults and traumatic damages of the brain.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):3-11
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Role of gut microbiota in the progression of HIV/AIDS infection
摘要
Acquired immune deficiency syndrome is the final stage of the progression of the infection induced by HIV. Without antiretroviral therapy, the period from the infection to the death of the patient lasts for about 10 years. The gut microbiota changes were proved to be one of the most important factor in the immune activation, local and system inflammation, as well as the progression of concomitant diseases. The aim of the review is to summarize the data describing the mechanisms of the influence of microbiome changes on the inflammation, immune activation, and HIV-associated complications. The original date of own investigations is presented too. The results confirm the endogenous way of Klebsiella infecting of AIDS patients due of the translocation from the gut.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):12-22
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Fucoidan as a component in the development of target systems for the delivery of medicinal substances
摘要
The growing interest in the group of highly sulfated heteropolysaccharides, defined as fucoidans, is due to a wide spectrum of their biological activity. The expansion of the direction of their application is associated with the search for applications in the development of medicinal materials, in particular, the targeted drug delivery system. The main types of nano- and microstructural systems created using fucoidan are objects formed by the electrostatic attraction forces of oppositely charged polyelectrolytes (layer-by-layer adsorption, polyelectrolyte complexes), emulsions, metal-polymer complexes. The use of fucoidan as a coating for bio magnets also allows its application in theranostics. The resulting carriers containing fucoidan, are applicable for targeted delivery of therapeutic agents such as doxorubicin, curcumin, poly-L-lysine, low molecular weight anti-TB drugs, etc. The shipping method also varies. There are developing carriers with the use of fucoidan for oral, inhalation, intravenous route of administration. However, such systems have low toxicity, are biodegradable. Degradation products do not accumulate in the body but are metabolized. In addition, it is possible to obtain a hollow matrix with a high degree of loading. All this will expand the possibilities of the use of this polysaccharide in the pharmaceutical industry and clinical therapy.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):23-29
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Correlation between cardiac troponin I levels and area of myocardial vascular necrosis in the patients with fatal outcome
摘要
Introduction. The scale of myocardial infarction plays a key role in the prognosis of the disease. Changes in contractile activity of myocardial tissue as a result of necrosis of cardiomyocytes is the decisive factor in this issue. The aim of the study. The purpose of this study was to assess the possibility of using a high-sensitive method for cardiac troponin I test for risk stratification of the patients with myocardial infarction and for clinico-morphological prediction of the development of the disease. Materials and methods. The study was conducted on the basis of cardiac surgery center and city patho-anatomical bureau. 89 patients with a fatal outcome were admitted to the hospital with a diagnosis of acute coronary syndrome during 2016 year. The level of cardiac troponin I was tested by high-sensitive chemiluminescent method on microparticles. Histological staining was by hematoxylin and eosin, by the method of Regaud, Lie, selectively performed the PAS reaction. Results. At the analysis of the correlation between cardiac troponin I concentration and size of myocardial infarcted area, the Spearman correlation coefficient was 0,57 (p<0.001), which according to the Chaddock scale corresponds to a moderate positive correlation. Patients with ECG ST segment elevation had statistically significantly higher concentrations of the cardiac marker and infarct sizes, the values of the Mann-Whitney U test are equal to U=140 atp<0.02 and U=117 atp<0.04, respectively. Conclusion. The results of the study showed the possibility of using a high sensitive troponin I as a reliable tool for establishing the correlation of cardiac troponin I levels by a highly sensitive method with the extent of damage to the cardiac muscle in patients with acute coronary syndrome and its effective use as a risk stratification in complex schemes.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):30-34
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Individual peculiarities of chromatin conformational state modification under exposure to different physical factors
摘要
Introduction. The difference in the responsibility of organisms’ influences on the results of biological experiments and medical intervention. The chromatin conformational state is one of the main factors determining the cell response to the effect of different factors. Aim of the study. Analysis of individual features of the chromatin conformation variation in a case of hyperthermia (heat shock), irradiation and exposure to the low-frequency magnetic field. Material and Methods. The research is performed using blood cells of white outbred male rats and human blood cells in vitro. The chromatic conformational state was determined with the help of the anomalous viscosity time dependence method. Results. The effect of the studied factors led to a stereotyped chromatin conformation change expressed as decondensation. The individual particulars in a case of heat shock and irradiation are manifested themselves in the dependence on the decondensation degree on the chromatin conformational state prior to the exposure. After the exposure to the magnetic field, the initial differences in the chromatin conformational state and reactivity indices became less expressed. Conclusion. There are individual differences in the chromatin conformation variations as a result of exposure to different factors and they determine the opportunity of predicting the individual features based on the initial conformational state evaluation.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):35-41
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Effect of regular aerobic physical load on the morphometric indicators of the visceral and subcutanial fat tissue of rats
摘要
Introduction. Excess and lack of adipose tissue are associated with a violation of its functions, the mass of adipose tissue and its distribution play an important role in the development of metabolic disorders. The study of the influence of the main factors of influence on adipose tissue - nutrition and physical activity are topical issues. The aim of the study. To assess the effect of aerobic exercise on the morphometric parameters of white adipose tissue of rats on the background of increased caloric intake (with a predominance of vegetable and animal fat in the diet). Methods. The experimentations were carried out on 64 male Wistar rats. Rats’ body mass, body length, body mass index, lean mass, specific weight of adipose tissue were estimated, adipocyte size. Results. Aerobic physical activity provided with high-calorie diet resulted in decrease of body mass, body mass index, lean mass and adipose tissue density. Abovementioned parameters changed proportionally in the group of animals with animal fat prevalence in nutrition, whereas more expressed decrease of adipose tissue mass due to subcutaneous fat was discovered in the group of animals with vegetable fat prevalence in nutrition. Reduction of adipocytes average size was observed with same prevalence in all adipose depots provided with animal fat prevalence nutrition. Reduction of average size of adipocytes of retroperitoneal and mesenteric adipose depots, provided with vegetable fat prevalence nutrition. Conclusion. Physical activity greatly influenced adipose tissue mass, qualitative and quantitative changes of average size of adipocytes in adipose depots are more effective provided with high vegetable fat content nutrition.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):42-46
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Fractional anisotropy estimation as a way to identify pathologies of the cerebral arterial system
摘要
Introduction. The correct functioning of the circulatory system allows providing stability of the brain and prevents the progression of pathological processes. The search for prognostic markers which make it possible to predict the appearance and adverse course of neurodegenerative diseases plays a key role in the vascular system research. The values indicating deviations in the blood supply to different regions or the organ as a whole relate to the topological characteristics of the vascular tree. The aim of the study was to identify the geometrical markers of the created vascular system, capable of indicating the possibility of the development of a pathological process in the organ under consideration. Methods. The model of the arterial tree of the rat brain was used as an experimental object in the work. The vascular network was structurally divided into deterministic and stochastic parts. The first part includes the main arteries that form the circle of Willis; the second one consists of the smaller vessels, realized in the form of a binary tree. The total bifurcation angles and fractional anisotropy which are the parameters characterizing the topological complexity of the network were estimated. The calculation of the fractional anisotropy of the constructed arterial systems was made on the basis of the standard methods using a weighted average covariance matrix. Results. It was shown that the value of the total bifurcation angle does not fall below the experimentally measured physiological threshold value (73°) in the constructed arterial model under the theoretically justified bifurcation exponent of 3.0. The value of the calculated fractional anisotropy in this case is equal to 0.014. With an increase in the bifurcation exponent, the vasculature becomes more isotropic, while vessels with a smaller caliber have a more uniform distribution density. Conclusion. The threshold value of fractional anisotropy corresponding to the physiologically correct arterial system was estimated on the basis of the total bifurcation angle. This parameter is proposed to be used as an indicator of vascular pathologies, since the experimental assessment of anisotropy is performed using the results of clinical studies and does not require additional manual segmentation, in contrast to the calculation of the bifurcation angles.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):47-52
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Frequency of the TERTRS2853669 polymorphism in melanoma patients residing in the eastern siberia region
摘要
Introduction. The telomerase reverse transcriptase gene (TERT) promoter region is frequently mutated in different types of cancer. Several studies have shown patients who carry the mutation -245T>C (rs2853669) to have a worse prognosis. The aim of the study is to analyze the frequency of the single nucleotide polymorphism (rs2853669) in melanoma patients and healthy cases possessing wild-type (TT) and variant (CT+CC) alleles residing in an Eastern Siberia region population in the Russian Federation. Methods. DNA was obtained from healthy volunteers and melanoma patients. The TERT rs2853669 polymorphism was determined based on the real time-PCR assay. Additionally, such characteristics as age, sex, Fitzpatrick skin phototype, eye and hair color, nevi count, localization of the tumor, and Breslow thickness) in melanoma patients were evaluated. Results. The frequency of the TERT single nucleotide polymorphism in the promoter region -245T>C (rs2853669) was found to be similar within both melanoma patients and healthy cases; these results correspond to other studies on TERT rs2853669 polymorphism distribution within European populations. Melanoma patients with blue eyes and blond hair were more frequent wild-type homozygotes. Conclusion. As increased telomerase activity is associated with the replicative immortality of melanocytes, -245T>C may affect melanogenesis and lead to an increased risk of the malignant transformation of cells.
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):53-56
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The effect of docetaxel on the survival and clonogenic activity of MCF-7 mammospheres culture enriched with cancer stem cells
摘要
Introduction. Cancer stem cells (CSCs), which are less sensitive to chemotherapeutic drugs than other tumor cells, play a key role in the initiation and development of the tumor process. Maintenance of CSCs determines the risk of cancer recurrence. The aim of the study. To study the effect of docetaxel on CSCs survival and self-renewal in the human mammary adenocarcinoma MCF-7 cells cultured as mammospheres. Methods. The effect of docetaxel on the CSCs survival was studied after 72 and 120 h of cultivation with the drug at concentrations of 0, 1, 10 and 100 nmol/l. For this purpose, the total number of living cells was counted, the fraction of CSCs with CD44+/CD24-/low phenotype was determined using flow cytometry, and the absolute number of CSCs was calculated in each sample. The effect of docetaxel on the CSCs repopulation was determined by counting mammospheres formed 7 days after cells were washed from docetaxel after 120 h cultivation with the drug at concentrations 0, 1, 10 and 100 nmol/l. Results. The cultivation of mammospheres with docetaxel for 72 h resulted in an insignificant decrease in both of the total cell number and the CSCs fraction. At the same time, there was a significant decrease in the number of CSCs. The cultivation of mammospheres at all studied docetaxel concentrations for 120 hours resulted in a significant decrease in the total number of cells, the proportion and the number of CSCs and their clonogenic activity that represents the ability of the CSC to repopulate. Conclusion. CSCs of MCF-7 mammospheres were shown to be highly sensitive to docetaxel after prolonged cultivation (120 h). Docetaxel inhibited the ability of CSCs to self-renewal, which plays a crucial role in the tumor and metastasis initiation
Molekulyarnaya Meditsina (Molecular medicine). 2019;17(5):57-63
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