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Vol 17, No 2 (2022)

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Molecular and genetic features of calpainopathy

Mkrtchyan L.A., Slesarenko Y.S., Yakovlev I.A., Bardakov S.N., Deev R.V.


Calpainopathy is the most common form of limb-girdle muscular dystrophy, prevalence in the population is approximately 1 in 15,000–42,700 individuals. In the Russian Federation, there is an insufficient number of studies, which researched prevalence of calpainopathy among patients with limb-girdle muscular dystrophy, but according to available data, approximately in 43% of cases the disease is associated with mutations of the CAPN3 gene. Molecular genetic analysis is the main method for diagnosing these patients. Studies indicate many pathogenic mutations that cause calpainopathy with corresponding phenotypes, however, it is quite difficult to establish clear correlations between genotype and phenotype due to the high variability of symptoms and severity, even among patients with the same CAPN3 gene mutations. Currently, there is no effective etiotropic treatment for limb-girdle muscular dystrophy, but new technologies are developing to improve patients’ condition and quality of life. This research collects data from various studies on the prevalence of calpainopathy in different countries and the main molecular genetic features of the CAPN3 gene and calpain-3 protein, which will further allow the development of possible treatment options for patients with limb–girdle muscular dystrophy.

Genes & Cells. 2022;17(2):6-13
pages 6-13 views

Comparison of histo- and organogenesis of human pancreas, white laboratory mouse and spiny mouse (Acomys)

Sultanova K.N., Titova A.A., Plushkina A.S., Andreeva D.I., Kiyasov A.P.


The study of the embryonic development of the pancreas gives the opportunity to understand the mechanisms of organ regeneration in case of various pathologies. Worldwide research works, studying histo- and organogenesis of human pancreas, are based on data, received from model animals. Numerous processes of pancreatic development take several hours and remain unclear because white laboratory mouse has short gestation period. Spiny mouse (Acomys) has the prolonged prenatal period and can be a convenient model to study the stages of histo- and organogenesis of the pancreas. The review analyzed similarities and differences in the structure of human pancreas, white laboratory mouse and spiny mouse, the features of prenatal histo- and organogenesis of the pancreas, which should be considered in conducting and interpreting results of fundamental research, and possibility of using of spiny mice as a model animal to study embryonic development and pathology of the pancreas.

Genes & Cells. 2022;17(2):14-19
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Effectiveness of cell and gene therapy in treatment of obliterating diseases of the arteries in the lower extremities: a review

Ha H.N., Chervyakov Y.V., Gavrilenko A.V.


The lack of significant progress in improving the results of treatment for patients with chronic lower limb ischemia (CLLI) determines a necessity to search new approaches to solve this problem. One of the promising methods for treatment of patients with CLLI is therapeutic angiogenesis. Gene and cell therapy clinical trials for this pathology have been carried out in the world for more than 20 years and showed conflicting results. It is extremely difficult to produce a drug based on cellular material, therefore the development of gene-based therapies is more promising. In most of the analyzed studies, patients with critical limb ischemia, i.e with initially with a high risk for major amputation, were included. Since the process of neoangiogenesis takes several months, it seems more logical to use that option for treatment in the earlier stages of the disease.

VEGF-165 is the most studied angiogenic agent. Only VEGF-165 is registered as a drug for treatment of patients with CLLI. There are publications on the effectiveness of treatment with a plasmid VEGF-165-gene therapy in patients with stages II and III of CLLI according to the Fontaine–A.V. Pokrovsky classification in a five-year follow-up study.

Genes & Cells. 2022;17(2):20-24
pages 20-24 views

Original Study Articles

IL-10 cytokine family secretion is associated with the activity of mitophagy components in visceral adipose tissue in obese with and without type 2 diabetes mellitus

Shunkina D.A., Dakhnevich A.Y., Komar A.A., Vulf M.A., Shunkin E.O., Gazatova N.D., Kirienkova E.V., Todosenko N.M., Malakhova Z.L., Litvinova L.S.


Autophagy is required to maintain cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids, and organelles. Impaired homeostasis of autophagic processes is associated with metabolic disorders such as obesity and type 2 diabetes mellitus. In obesity, a violation of autophagy in adipose tissue and its inflammation contributes to the formation of type 2 diabetes mellitus.

The aim of the study was to analyze the expression of autophagy genes in the adipose tissue of the greater omentum and to search for their relationship with the levels of cytokines of the IL-10 family in blood plasma in obese patients, depending on the presence or absence of type 2 diabetes mellitus.

Blood plasma and visceral adipose tissue samples were studied from 347 obese patients with and without type 2 diabetes. A biochemical analysis of the patients' blood was carried out. The level of cytokines was detected by flow fluorometry. Gene expression was determined by real-time PCR, and tissue-specific protein production was determined by immunoblotting. Statistical processing of the results was carried out using GraphPad Prism 9.0.0 software.

Plasma levels of IL-10, IL-20, IL-22, IL-28A, and IL-29 are increased in obese patients without type 2 diabetes compared with patients with type 2 diabetes. In patients with type 2 diabetes mellitus, the expression of the SQSTM1_p62 and MAP1LC3B genes in the greater omentum increased compared to patients without it.

High plasma levels of IL-22 and IL-26 are associated with the presence of type 2 diabetes mellitus. In patients without type 2 diabetes mellitus, an increase in the level of IL-28A in blood plasma is associated with a decrease in the expression of autophagy genes SQSTM1_p62 and MAP1LC3B in the adipose tissue of the greater omentum.

Genes & Cells. 2022;17(2):25-31
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Angiogenic properties of glial progenitor cells derived from human induced pluripotent stem cells

Salikhova D.I., Khaerdinova L.R., Makhnach O.V., Goldshtein D.V.


Diseases associated with impaired blood supply to the brain ranks second term of mortality in the world, losing the place only to coronary heart disease. The incidence of this disease in the world remains high and increasing significantly with the age. The recent year’s special attention has been paid to the search for new methods of therapy for ischemic diseases, such as study of angiogenic properties of stem cells and their conditioned medium. The aim of this work is studying the angiogenic properties of glial progenitor cells derived from human induced pluripotent stem cells. The study was carried out by testing the proliferative activity, mobility, migration of endothelial cells line EA.hy926 under the influence of glial progenitor cells and their conditioned medium. Also the research was conducted by ability to formation of the tubular and capillary-like structure by cells line EA.hy926 by modeling angiogenesis in the basement membrane matrix in vitro.

The conditioned medium obtained by glial progenitor cells at concentrations of total protein 1 and 5 µg/ml has a positive influence on the proliferative activity and mobility of the endothelial cells line EA.hy926. At the same time it does not accelerate the formation of the primary tubular and capillary-like structure by the modeling angiogenesis in the basement membrane matrix in vitro. But glial progenitor cells contribute to the formation of tubular and capillary-like structure due to contact-dependent signaling between the two cell types. The primary formed tubular structure had a long processes and large branch points under co — cultivation with glial progenitor cells. Sprouting centers also had long and more convoluted processes and large cell clusters during the formation of a capillary-like structure. The glial progenitor cells and their conditioned medium had a positive effect on endothelial cell migration. This effect probably indicated by the production of substances by glial progenitor cells which was chemoattractants for endothelial cells line EA.hy926.

Genes & Cells. 2022;17(2):32-39
pages 32-39 views

Proliferative activity of cancer stem cells in the prognosis of hematogenous metastasis of colon adenocarcinoma

Erokhina A.A., Chirsky V.S., Maistrenko N.A., Sazonov A.A., Grigorev S.G.


The search for prognostic markers to determine the risk of dissemination and metastasis of colon adenocarcinoma is one of the most difficult and actual problems of modern oncomorphology.The aim of this work was to determine the possibility of using indicators of the proliferative activity of cancer stem cells in the prediction of hematogenous metastasis of colon adenocarcinoma.

In this work the surgical material from 32 radically operated patients of different ages suffering from a localized colon adenocarcinoma was explored, and relapse-free survival was assessed. A comparative analysis of various components of the tumor differon, including proliferating stem cells and their relationship with the formation of relapse was carried out.An index of stem cell proliferation was proposed to assess the influence of stem cell activity on the biological behavior of tumor.

The best rates of relapse-free survival were found in the group of patients with low value of the index of stem cell proliferation compared with patients which index took on high values, which is more typical for elderly and old patients. With a similar comparison of other indicators of tumor differon, including the percentage of ALDH1 and Ki-67-positive cells, as well as cells with the ALDH1+Ki-67+immenophenotype relative to the total tumor differon, no significant relationship with relapse-free survival was found.

These results may indicate a high role of ALDH1+ cell proliferation in tumor dissemination, especially in elderly and senile patients, and a lesser influence of both the proliferative activity of Ki-67 and the general population of stem cells on the formation of distant metastases.

Genes & Cells. 2022;17(2):40-46
pages 40-46 views

TB skin test recombinant proteins as vaccine candidates

Krasilnikov I.V., Vinogradova T.I., Djonovic M., Zabolotnykh N.V., Arakelov S.A., Dogonadze M.Z., Lunin V.G.


Incomplete protection of BCG vaccines, high variability of tuberculosis strains, together with the growing antibiotic resistance of mycobacterium tuberculosis, actualize the need to develop new anti-tuberculosis vaccines. Several novel experimental candidate vaccines based on recombinant proteins, such as those based on the M. tuberculosis ESAT-6 and CFP-10 antigens, are currently being studied in clinical trials. The genome region coding for ESAT-6 and CFP-10 antigens is deleted in BCG strains, so the BCG-immunized individuals cannot develop an immune response against the recombinant ESAT-6/CFP-10 antigen. Therefore, a positive immune reaction to these antigens in TB tests indicates the tested individual has earlier been exposed to M. tuberculosis. The ESAT-6/CFP-10 fusion recombinant antigen was, thus, selected as an immunogen to be evaluated on its potential to induce protective immunity against tuberculosis in a mice model when combined with a birch bark betulin-based vaccine adjuvant. The effect of use was assessed based on the results of histological evaluation of the infected lung tissue in mice and the Mtb lung content. The results herein reported eventually demonstrated that the use of corpuscular adjuvant-based (betulin) ESAT-6/CFP-10 vaccine preparation can induce the immune response commensurate to that of when immunized with the BCG vaccine.

Genes & Cells. 2022;17(2):47-55
pages 47-55 views

The role of polymorphic variants of the ERCC2 excision repair gene in the pathogenesis of ovarian cancer in women of different ethnic origins

Valova Y.V., Mingazheva E.T., Prokofieva D.S., Andreeva E.A., Nurgalieva A.K., Ekomasova N.V., Khusnutdinova E.K.


Malignant neoplasms of the ovaries are one of the most frequently diagnosed tumors of the female reproductive system and one of the leading causes of cancer death in women worldwide. Despite significant advances in the field of early diagnosis and treatment of the disease, the survival rate of patients with this form of oncopathology is still low, which dictates the need for further study of this problem. The aim of the work was to evaluate the role of polymorphic variants rs13181 and rs238406 of the ERCC2 gene in the development of hereditary and sporadic forms of ovarian cancer in women of different ethnicity from the Republic of Bashkortostan. The material for the study was DNA samples of women with sporadic forms of ovarian cancer (n=182), hereditary forms of ovarian cancer (n=65) and women without cancer at the time of blood sampling (n=292) of various ethnic origins. Genotyping was performed by polymerase chain reaction (PCR) followed by analysis of restriction fragment length polymorphism. As a result of the study, an association of the rs13181*C allele of the ERCC2 gene with the risk of developing hereditary and sporadic forms of ovarian cancer in women of Russian ethnicity was established. An association of the rs238406*GT genotype of the ERCC2 gene with the risk of developing sporadic forms of ovarian cancer was revealed. The data obtained indicate the involvement of the studied polymorphic variants in the pathogenesis of ovarian cancer in our region.

Genes & Cells. 2022;17(2):56-59
pages 56-59 views

Influence of some metabolites from plants of the genus Petasítes sp. on cancer cells motility in vitro

Filippova S.Y., Shamova T.V., Timofeeva S.V., Sitkovskaya A.O., Mezhevova I.V., Gnennaya N.V., Novikova I.A., Enin Y.S., Burov O.N., Zlatnik E.Y., Mezentsev S.S., Chernikova E.N., Pandova O.V., Pozdnyakova V.V., Ezhova M.O., Bakulina S.M., Khokhlova O.V.


Secondary plant metabolites are a promising source of anticancer drugs. Of particular interest are substances that can reduce the migration activity of cancer cells as potential anti-metastatic drugs. In present work we study the influence of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one, 5-(hydroxymethyl)furan-2-carbaldehyde and corinan obtained from plants of the genus Petasítes sp. on scratch healing rate of permanent cancer lines PC3, A431, CaCo2, HeLa, and T98G. Cells were grown in DMEM medium supplemented with 10% FBS. To perform a scratch test, cells were planted in an amount of 1,5×105 per well of a 24-well plate. After cell adhesion, a vertical scratch was applied to the cell monolayer with a plastic tip, after which the medium containing the test substances at a concentration of 40 µM was added. Then, within 48 hours, photographing and determining the scratch area were carried out. The degree of scratch overgrowth was determined as the ratio of the difference between the scratch areas after 48 hours of cultivation and the scratch area at the initial moment, expressed as a percentage. As a result of the experiment, it was shown that 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one downregulates scratch healing rate in cultures A431, HeLa, T98G. The high sensitivity of A431 to corinan was also shown.

Genes & Cells. 2022;17(2):60-63
pages 60-63 views

Dynamics of inflammatory infiltrate in mice liver under conditions of experimental fecal peritonitis

Safronova G.M., Indeikin F.A., Andreev Y.A., Emelin A.M., Presnyakov E.V., Deev R.V.


The relationship between the liver and the peritoneum is an important element in a body homeostasis maintaining. Morphofunctional changes occurring in the liver in response to fecal peritonitis allow a better understanding of this relationship. Despite the existing researches, some aspects of the pathological changes occurring in the liver in fecal peritonitis require a special study.

Purpose: to describe the composition and dynamics of the lymphocytic-leukocytic infiltrate in the liver in conditions of experimental fecal peritonitis.

The study was conducted on Balb/c (n=5) mice with artificially induced fecal peritonitis. One animal was euthanized on 1, 3, 5, 7 and 14 day of the experiment. Immunophenotyping of inflammatory infiltrate cells was performed on liver tissue samples using antibodies to CD3, CD45, CD163. Morphometric analysis was carried out with the calculation of the number of cells per unit area.

It was shown that the highest intensity of infiltration by CD45+-cells is observed on the 3rd day of the experiment with a subsequent decrease; infiltration by CD3+-cells increases by the 5th day of the experiment without further dynamics; infiltration of CD163+-cells — by day 7 without further changes.

Conclusions: the severity of the liver parenchyma infiltration by immune cells in dynamics reflects the organ reaction to experimental fecal peritonitis.

Genes & Cells. 2022;17(2):64-66
pages 64-66 views

Discussion and general theoretical works

Morphogenesis of the gall bladder — a mystery of the XXI century

Oripov F.S., Dekhkanov T.D.


This discussion article presents the theoretical background and results of our own histological study of the ampulla of the papilla of Vater in various animals to explain the absence of the gallbladder in some animals. In particular, the authors studied the structure of the duodenal mucosa in rats and rabbits. They suggest that the evolutionary loss of the gallbladder in some animals is associated with the need for rapid movement in space and high maneuverability. The realization of these properties may be hindered by a fluid-filled organ.

Genes & Cells. 2022;17(2):67-69
pages 67-69 views

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