A. S. Khaliullina, Dilyara Kh. Shakirova, Leysan A. Aliullina, Olga V. Morgatskaya
COVID-19 is an acute respiratory viral infection caused by the coronavirus SARS-CoV-2 (2019-nCoV). Currently, approaches to coronavirus infusion are mostly confined to pathogenetic and symptomatic therapy. New treatment strategies include research to find new molecul candidates for COVID-19 treatment, as well as the repositioning of existing medicinal products. Recently, medicinal plants have been actively studied as potential candidates for COVID-19 treatment, showing high levels of antiviral activity and anti-inflammatory activity. This review focuses on medicinal plants whose biologically active substances are used or can be used for the treatment and the supportive therapy for a new coronavirus infection.
{"title":"Application of herbal medicinal raw material in complex treatment COVID-19","authors":"A. S. Khaliullina, Dilyara Kh. Shakirova, Leysan A. Aliullina, Olga V. Morgatskaya","doi":"10.17816/maj108571","DOIUrl":"https://doi.org/10.17816/maj108571","url":null,"abstract":"COVID-19 is an acute respiratory viral infection caused by the coronavirus SARS-CoV-2 (2019-nCoV). Currently, approaches to coronavirus infusion are mostly confined to pathogenetic and symptomatic therapy. New treatment strategies include research to find new molecul candidates for COVID-19 treatment, as well as the repositioning of existing medicinal products. Recently, medicinal plants have been actively studied as potential candidates for COVID-19 treatment, showing high levels of antiviral activity and anti-inflammatory activity. This review focuses on medicinal plants whose biologically active substances are used or can be used for the treatment and the supportive therapy for a new coronavirus infection.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"130 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115674954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. N. Kisakov, L. A. Orlova, Сергей V. Sharabrin, A. Rudometov, M. Borgoyakova, E. Starostina, L. Karpenko, A. Ilyichev
BACKGROUND: Nucleic acid-based prevention tools provide a promising platform for developing vaccines, including those against COVID-19. Previously, we developed the pVAXrbd DNA vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2, which, when administered intramuscularly to animals, induced a relatively weak immune response. The next stage of the study is to increase the immune response, in particular, using electroporation as one of the methods for increasing the immunogenicity of DNA vaccines. AIM: The aim of this article is to evaluate the immune response using electroporation in mice after immunization with pVAXrbd. MATERIALS AND METHODS: BALB/c mice were immunized with pVAXrbd using direct and reverse polarity square wave direct current electroporation with three pulses of 12 V for 30 ms and an interval of 950 ml with a current limit of 45 mA. RESULTS: BALB/c mice were immunized twice with an interval of three weeks with a dose of 100 g of DNA. Using ELISA, the titers of RBD-specific antibodies in the group of animals immunized with pVAXrbd using electroporation were 1:109350, which is 16 times higher than in the group of animals that received the DNA vaccine only intramuscularly (titers 1:6750). IFN ELISpot analysis showed that the largest number of cells (2434 spots/splenocytes, million) producing IFN in response to stimulation with peptides from the RBD protein was registered in the group of animals immunized with pVAXrbd using electroporation. For comparison, in the control group, the number of cells is 6.5 times lower: 380 spots / splenocytes, mln. CONCLUSIONS: Administration of the pVAXrbd DNA vaccine to laboratory animals by electroporation significantly enhances both the humoral and cellular specific immune response compared to intramuscular administration of the naked DNA vaccine.
背景:基于核酸的预防工具为开发疫苗提供了一个有前景的平台，包括针对COVID-19的疫苗。之前，我们开发了编码SARS-CoV-2受体结合域(RBD)的pVAXrbd DNA疫苗，当给动物肌肉注射时，诱导了相对较弱的免疫反应。研究的下一阶段是增加免疫反应，特别是使用电穿孔作为增加DNA疫苗免疫原性的方法之一。目的:用电穿孔法评价pVAXrbd免疫小鼠后的免疫反应。材料与方法:采用正反极性方波直流电穿孔法对BALB/c小鼠进行pVAXrbd免疫，脉冲为12 V，间隔为950 ml，电流限为45 mA。结果:BALB/c小鼠用100 g DNA免疫2次，间隔3周。ELISA检测结果显示，pVAXrbd电穿孔免疫组的rbd特异性抗体滴度为1:109350，是仅肌内注射DNA疫苗组(滴度为1:6750)的16倍。IFN ELISpot分析显示，电穿孔pVAXrbd免疫动物组在RBD蛋白肽刺激下产生IFN的细胞数量最多(2434个斑点/脾细胞，百万)。相比之下，对照组的细胞数量减少了6.5倍:380个斑点/脾细胞，百万。结论:与裸DNA疫苗肌肉注射相比，通过电穿孔给药pVAXrbd DNA疫苗可显著增强实验动物的体液和细胞特异性免疫反应。
{"title":"Delivery of a DNA vaccine encoding SARS-CoV-2 receptor-binding domain (RBD) by electroporation","authors":"D. N. Kisakov, L. A. Orlova, Сергей V. Sharabrin, A. Rudometov, M. Borgoyakova, E. Starostina, L. Karpenko, A. Ilyichev","doi":"10.17816/maj108614","DOIUrl":"https://doi.org/10.17816/maj108614","url":null,"abstract":"BACKGROUND: Nucleic acid-based prevention tools provide a promising platform for developing vaccines, including those against COVID-19. Previously, we developed the pVAXrbd DNA vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2, which, when administered intramuscularly to animals, induced a relatively weak immune response. The next stage of the study is to increase the immune response, in particular, using electroporation as one of the methods for increasing the immunogenicity of DNA vaccines. \u0000AIM: The aim of this article is to evaluate the immune response using electroporation in mice after immunization with pVAXrbd. \u0000MATERIALS AND METHODS: BALB/c mice were immunized with pVAXrbd using direct and reverse polarity square wave direct current electroporation with three pulses of 12 V for 30 ms and an interval of 950 ml with a current limit of 45 mA. \u0000RESULTS: BALB/c mice were immunized twice with an interval of three weeks with a dose of 100 g of DNA. Using ELISA, the titers of RBD-specific antibodies in the group of animals immunized with pVAXrbd using electroporation were 1:109350, which is 16 times higher than in the group of animals that received the DNA vaccine only intramuscularly (titers 1:6750). IFN ELISpot analysis showed that the largest number of cells (2434 spots/splenocytes, million) producing IFN in response to stimulation with peptides from the RBD protein was registered in the group of animals immunized with pVAXrbd using electroporation. For comparison, in the control group, the number of cells is 6.5 times lower: 380 spots / splenocytes, mln. \u0000CONCLUSIONS: Administration of the pVAXrbd DNA vaccine to laboratory animals by electroporation significantly enhances both the humoral and cellular specific immune response compared to intramuscular administration of the naked DNA vaccine.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114430138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Shtro, A. V. Galochkina, Y. Nikolaeva, Anzhelika V. Garshinina, Daria N. Razgulyaeva, K. Ponomarev, Evgeny S. Mozhaytsev, E. V. Suslov, K. Volcho, N. Salakhutdinov
BACKGROUND: Respiratory syncytial infection annually affects large segments of the population around the world. Despite the ease of clinical manifestations in most adults, for children under two years of age, this disease is a serious danger, leading to the development of severe bronchiolitis, even death. AIM: The aim of this study was to search for drugs with antiviral activity among adamantane derivatives. MATERIALS AND METHODS: Preparations of the group of adamantane derivatives were synthesized in the Department of Medicinal Chemistry of Natural Compounds of the N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS. The cytotoxicity and antiviral activity of the compounds were studied in HEp-2 cell culture using the MTT test and enzyme immunoassay, respectively. RESULTS: There were no drugs with high antiviral properties against RSV in this group. CONCLUSIONS: Despite the absence of drugs with pronounced anti-RSV properties, the information obtained in the course of the work can be used for a targeted search for antitumor substances.
{"title":"Antiviral activity of adamantane derivatives against respiratory syncytial virus","authors":"A. Shtro, A. V. Galochkina, Y. Nikolaeva, Anzhelika V. Garshinina, Daria N. Razgulyaeva, K. Ponomarev, Evgeny S. Mozhaytsev, E. V. Suslov, K. Volcho, N. Salakhutdinov","doi":"10.17816/maj108808","DOIUrl":"https://doi.org/10.17816/maj108808","url":null,"abstract":"BACKGROUND: Respiratory syncytial infection annually affects large segments of the population around the world. Despite the ease of clinical manifestations in most adults, for children under two years of age, this disease is a serious danger, leading to the development of severe bronchiolitis, even death. \u0000AIM: The aim of this study was to search for drugs with antiviral activity among adamantane derivatives. \u0000MATERIALS AND METHODS: Preparations of the group of adamantane derivatives were synthesized in the Department of Medicinal Chemistry of Natural Compounds of the N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS. The cytotoxicity and antiviral activity of the compounds were studied in HEp-2 cell culture using the MTT test and enzyme immunoassay, respectively. \u0000RESULTS: There were no drugs with high antiviral properties against RSV in this group. \u0000CONCLUSIONS: Despite the absence of drugs with pronounced anti-RSV properties, the information obtained in the course of the work can be used for a targeted search for antitumor substances.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123464036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna K. Chistyakova, E. Stepanova, I. Isakova-Sivak, L. Rudenko
BACKGROUND: The rapid spread of SARS-CoV-2 virus, which caused the COVID-19 pandemic, and the emergence of new co-circulating antigenic variants require the development and update of subtyping kits and protocols. Pyrosequencing-based protocols are promising approach for detection of single nucleotide polymorphisms. AIM: In this study we designed the assays for genotyping Variants of Concern of the SARS-CoV-2 coronavirus using polymerase chain reaction, followed by determination of the virus variant in the sample by pyrosequencing. MATERIALS AND METHODS: Pyrosequencing assays were designed based on alignment of SARS-CoV-2 sequences. Testing was performed using RNA of SARS-CoV-2 viruses of different lineages (alpha, beta, gamma, delta, and omicron). Pyrosequencing was performed using the PyroMark Q24 system. RESULTS: The protocols of sample preparation and pyrosequencing were developed and tested for sequencing of regions encoding substitutions in amino acid positions: L18F, T19R, T20N; A67V, 69-70; G142D, 143-145; 156-157, R158G; 242-244; K417N/T; L452R; S477N, T478K, E484A/K/Q; H655Y; N679K, P681H/R. The specificity of the system was also evaluated in reactions with a negative control sample (RNA isolated from human nasal swab). CONCLUSIONS: In this study, we developed and initially tested protocol for detecting coronavirus variants (alpha, beta, gamma, delta, and omicron) from samples collected from cell culture, based on the PCR technique, followed by genotyping of the variants by pyrosequencing with PyroMark Q24. The developed protocols may be adjusted to the current epidemiological situation by increasing the number of detectable sites.
{"title":"Development of pyrosequencing-based assay for genotyping of different coronavirus variants","authors":"Anna K. Chistyakova, E. Stepanova, I. Isakova-Sivak, L. Rudenko","doi":"10.17816/maj108988","DOIUrl":"https://doi.org/10.17816/maj108988","url":null,"abstract":"BACKGROUND: The rapid spread of SARS-CoV-2 virus, which caused the COVID-19 pandemic, and the emergence of new co-circulating antigenic variants require the development and update of subtyping kits and protocols. Pyrosequencing-based protocols are promising approach for detection of single nucleotide polymorphisms. \u0000AIM: In this study we designed the assays for genotyping Variants of Concern of the SARS-CoV-2 coronavirus using polymerase chain reaction, followed by determination of the virus variant in the sample by pyrosequencing. \u0000MATERIALS AND METHODS: Pyrosequencing assays were designed based on alignment of SARS-CoV-2 sequences. Testing was performed using RNA of SARS-CoV-2 viruses of different lineages (alpha, beta, gamma, delta, and omicron). Pyrosequencing was performed using the PyroMark Q24 system. \u0000RESULTS: The protocols of sample preparation and pyrosequencing were developed and tested for sequencing of regions encoding substitutions in amino acid positions: L18F, T19R, T20N; A67V, 69-70; G142D, 143-145; 156-157, R158G; 242-244; K417N/T; L452R; S477N, T478K, E484A/K/Q; H655Y; N679K, P681H/R. The specificity of the system was also evaluated in reactions with a negative control sample (RNA isolated from human nasal swab). \u0000CONCLUSIONS: In this study, we developed and initially tested protocol for detecting coronavirus variants (alpha, beta, gamma, delta, and omicron) from samples collected from cell culture, based on the PCR technique, followed by genotyping of the variants by pyrosequencing with PyroMark Q24. The developed protocols may be adjusted to the current epidemiological situation by increasing the number of detectable sites.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124331523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Kirillov, L. Makartseva, M. A. Kozlova, Marina V. Muratova, I. Chernov, D. Areshidze
BACKGROUND: Violation of the lighting regime, as well as alcohol abuse, is significant factors in the disorganization of biorhythms in the modern world. Violation of rhythm leads to a mismatch of body functions, as a result to disadaptation, the occurrence of desynchronosis and the development of a number of socially significant diseases. AIM: Study of influence of constant lighting, chronic alcohol intoxication and joint action of these factors on diurnal dynamics of several electrolytes in blood of rats. MATERIALS AND METHODS: The study was conducted on 160 male of Wistar outbred stock at age of 6 months, with body weight of 300 20 g, which were divided into 4 groups. Control group animals, which were kept under conditions of fixed light regime (light:darkness = 10:14 hours), I group animals, which were kept under conditions of fixed light regime, but received a 15% water solution of ethanol as a drink, II group animals, which were kept under conditions of constant light regime, III group animals, which were kept under conditions of constant light regime and received a 15% water solution of ethanol as a drink. In blood samples, taken at 9:00, 15:00, 21:00 and 3:00 oclock, the concentration of total calcium, potassium, sodium, chlorine and phosphorus was measured. The reliability of circadian rhythmicity was determined through cosinor analysis. RESULTS: The increase in the concentration of phosphorus in the blood plasma of animals of II and III experimental groups was found with the decrease in the concentration of total calcium in animals of I and III experimental groups. Constant lighting and chronic alcohol intoxication affect the amplitude-phase characteristics of the circadian rhythms of all studied ions, and the combined action of these factors causes the destruction of the circadian rhythms of the studied electrolytes. CONCLUSIONS: It is established that the three-weeks-long influence of the studied chronodestructors leads to disruptions in metabolism of calcium and phosphorus, which are the most pronounced at joint action of darkness deprivation and chronic alcohol intoxication, and also to the significant disruptions in the structure of CRs of all of studied substances.
{"title":"Diurnal dynamics of rat blood electrolytes at constant lighting and chronic alcohol intoxication","authors":"Y. Kirillov, L. Makartseva, M. A. Kozlova, Marina V. Muratova, I. Chernov, D. Areshidze","doi":"10.17816/maj105272","DOIUrl":"https://doi.org/10.17816/maj105272","url":null,"abstract":"BACKGROUND: Violation of the lighting regime, as well as alcohol abuse, is significant factors in the disorganization of biorhythms in the modern world. Violation of rhythm leads to a mismatch of body functions, as a result to disadaptation, the occurrence of desynchronosis and the development of a number of socially significant diseases. \u0000AIM: Study of influence of constant lighting, chronic alcohol intoxication and joint action of these factors on diurnal dynamics of several electrolytes in blood of rats. \u0000MATERIALS AND METHODS: The study was conducted on 160 male of Wistar outbred stock at age of 6 months, with body weight of 300 20 g, which were divided into 4 groups. Control group animals, which were kept under conditions of fixed light regime (light:darkness = 10:14 hours), I group animals, which were kept under conditions of fixed light regime, but received a 15% water solution of ethanol as a drink, II group animals, which were kept under conditions of constant light regime, III group animals, which were kept under conditions of constant light regime and received a 15% water solution of ethanol as a drink. In blood samples, taken at 9:00, 15:00, 21:00 and 3:00 oclock, the concentration of total calcium, potassium, sodium, chlorine and phosphorus was measured. The reliability of circadian rhythmicity was determined through cosinor analysis. \u0000RESULTS: The increase in the concentration of phosphorus in the blood plasma of animals of II and III experimental groups was found with the decrease in the concentration of total calcium in animals of I and III experimental groups. Constant lighting and chronic alcohol intoxication affect the amplitude-phase characteristics of the circadian rhythms of all studied ions, and the combined action of these factors causes the destruction of the circadian rhythms of the studied electrolytes. \u0000CONCLUSIONS: It is established that the three-weeks-long influence of the studied chronodestructors leads to disruptions in metabolism of calcium and phosphorus, which are the most pronounced at joint action of darkness deprivation and chronic alcohol intoxication, and also to the significant disruptions in the structure of CRs of all of studied substances.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116201519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND: Neuroinflammation is a significant component of the pathogenesis of cerebral ischemia. The JNK and NF-B signaling pathways play a leading role in the progression of brain tissue inflammation, which may represent a promising target for therapeutic effects. AIM: To evaluate the effect of new derivatives of 3-formylchromone on the course of neuroinflammation reactions and the activity of JNK and NF-B translational pathways in brain tissue in rats with cerebral ischemia. MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible right-sided occlusion of the middle cerebral artery. The studied compounds and the reference (ethylmethylhydroxypyridine succinate) were administered per os at doses of 30 and 100 mg/kg, respectively. After 72 hours of ischemia, changes in the concentration of proinflammatory cytokines were evaluated in the cerebrospinal fluid: IL-6, IL-1, IL-8 and TNF-. The content of JNK and NF-B in brain tissue was determined by enzyme immunoassay. RESULTS: The use of the test compounds 3FC1, 3FC2, 3FC4 and 3FC5, as well as the reference medicine, contributed to a decrease in the content of proinflammatory markers in the liquor. At the same time, the most significant decrease was noted when the compound 3FC5 was administered to animals, namely, the concentration of IL-1, IL-6, IL-8 and TNF- was lower relative to similar indicators of the group of animals without treatment by 30.0% (p 0.05); 64.5% (p 0.05); 48.5% (p 0.05) and 56.6% (p 0.05), respectively. The use of the fluorine-containing compound 3FC3 did not significantly affect the course of brain tissue inflammation reactions in rats. Evaluation of changes in the activity of JNK and NF-B showed that the studied substances inhibit the NF-B translational pathway and do not affect JNK, which is probably due to the activation of these signaling pathways and the antioxidant potential of the studied molecules. CONCLUSIONS: The use of compounds that are derivatives of 3-formylchromone in conditions of experimental cerebral ischemia contributes to the reduction of neuroinflammation reactions by inhibiting the NF-B pathway, without affecting the activity of the JNK-dependent signaling system. The substance with the highest pharmacological effects is the compound 3FC5, which contains a spatially hindered phenolic hydroxyl in its structure.
{"title":"Effect of 3-formylchromone derivatives on neuroinflammation reactions and JNK and NF-κB regulatory pathways","authors":"D. Pozdnyakov","doi":"10.17816/maj97256","DOIUrl":"https://doi.org/10.17816/maj97256","url":null,"abstract":"BACKGROUND: Neuroinflammation is a significant component of the pathogenesis of cerebral ischemia. The JNK and NF-B signaling pathways play a leading role in the progression of brain tissue inflammation, which may represent a promising target for therapeutic effects. \u0000AIM: To evaluate the effect of new derivatives of 3-formylchromone on the course of neuroinflammation reactions and the activity of JNK and NF-B translational pathways in brain tissue in rats with cerebral ischemia. \u0000MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible right-sided occlusion of the middle cerebral artery. The studied compounds and the reference (ethylmethylhydroxypyridine succinate) were administered per os at doses of 30 and 100 mg/kg, respectively. After 72 hours of ischemia, changes in the concentration of proinflammatory cytokines were evaluated in the cerebrospinal fluid: IL-6, IL-1, IL-8 and TNF-. The content of JNK and NF-B in brain tissue was determined by enzyme immunoassay. \u0000RESULTS: The use of the test compounds 3FC1, 3FC2, 3FC4 and 3FC5, as well as the reference medicine, contributed to a decrease in the content of proinflammatory markers in the liquor. At the same time, the most significant decrease was noted when the compound 3FC5 was administered to animals, namely, the concentration of IL-1, IL-6, IL-8 and TNF- was lower relative to similar indicators of the group of animals without treatment by 30.0% (p 0.05); 64.5% (p 0.05); 48.5% (p 0.05) and 56.6% (p 0.05), respectively. The use of the fluorine-containing compound 3FC3 did not significantly affect the course of brain tissue inflammation reactions in rats. Evaluation of changes in the activity of JNK and NF-B showed that the studied substances inhibit the NF-B translational pathway and do not affect JNK, which is probably due to the activation of these signaling pathways and the antioxidant potential of the studied molecules. \u0000CONCLUSIONS: The use of compounds that are derivatives of 3-formylchromone in conditions of experimental cerebral ischemia contributes to the reduction of neuroinflammation reactions by inhibiting the NF-B pathway, without affecting the activity of the JNK-dependent signaling system. The substance with the highest pharmacological effects is the compound 3FC5, which contains a spatially hindered phenolic hydroxyl in its structure.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131055502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. S. Belousova, Z. I. Mikashinowich, E. Vinogradova
BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin. AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin. MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) intact animals; comparison group (35 animals) intact animals treated with simvastatin for two months; experimental group divided into: subgroup 1 (35 individuals) animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied. RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins. CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.
{"title":"Metabolic and structural changes in the myocardium of rats with hypercholesterolemia after prolonged administration of simvastatin","authors":"E. S. Belousova, Z. I. Mikashinowich, E. Vinogradova","doi":"10.17816/maj89930","DOIUrl":"https://doi.org/10.17816/maj89930","url":null,"abstract":"BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin. \u0000AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin. \u0000MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) intact animals; comparison group (35 animals) intact animals treated with simvastatin for two months; experimental group divided into: subgroup 1 (35 individuals) animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied. \u0000RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins. \u0000CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133699683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The main reason for the low efficiency of glioblastoma therapy is its resistance to therapeutic procedures. The development of multidrug resistance occurs as a result of the selection of tumor clones during therapy. The resistant cell clones to radiotherapy and chemotherapy can proliferate, leading to tumor growth, in which its own vascular network is formed (angiogenesis), which promotes cell migration, invasion and the appearance of metastases and recurrent glioblastoma. The review examines the relationship at the molecular level of multidrug resistance with proliferation, angiogenesis, migration, metastasis, and the formation of glioblastoma relapses, with an emphasis on identifying new targets among proteins, microRNAs, signal transduction kinases, transcription factors, tumor-supressor genes and oncogenes.
{"title":"Molecular mechanisms of drug resistance of glial tumor of brain. Part 2: Proliferation, angiogenesis, metastasis and recurrency","authors":"A. Chernov, E. Galimova, O. Shamova","doi":"10.17816/maj83594","DOIUrl":"https://doi.org/10.17816/maj83594","url":null,"abstract":"The main reason for the low efficiency of glioblastoma therapy is its resistance to therapeutic procedures. The development of multidrug resistance occurs as a result of the selection of tumor clones during therapy. The resistant cell clones to radiotherapy and chemotherapy can proliferate, leading to tumor growth, in which its own vascular network is formed (angiogenesis), which promotes cell migration, invasion and the appearance of metastases and recurrent glioblastoma. The review examines the relationship at the molecular level of multidrug resistance with proliferation, angiogenesis, migration, metastasis, and the formation of glioblastoma relapses, with an emphasis on identifying new targets among proteins, microRNAs, signal transduction kinases, transcription factors, tumor-supressor genes and oncogenes.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":" 25","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133053119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUND: Identification of possible biomarkers that assess the severity of post-traumatic stress symptoms is an urgent task for the early diagnosis of post-traumatic stress disorders. The manifestation of emotional states, both human and animal, is reflected in altered behavior and in the violation of the ratio of basic rhythms and cross-correlation connections in the brain electroencephalogram, which indicates the development of pathological processes. AIM: The aim of the study was to analyze the behavior and electrocorticogram indicators of rats in the delayed period (on day 7) after life-threatening stress, as a way to predict the formation of post-traumatic stress disorder. MATERIALS AND METHODS: The study was performed on mature female Wistar rats weighing 180200 g (n = 40). Mental trauma was modeled by the circumstances of experiencing the situation of the death of a partner from the action of a predator and the threat to their own life when placing rats in a terrarium with a tiger python. In rats, the behavior in the Open Field test and the bioelectric activity of the brain in the frontal and occipital regions on the left and right were analyzed before and on the 7th day after stress exposure. RESULTS: It is shown that in the delayed period after vital stress in female rats, there is a decrease in motor and research activity and altered emotional behavior in the Open Field test. Reduction of interhemispheric asymmetry in the index of theta and delta activity and changes in cross-correlation connections in the right hemisphere, as well as changes in the ratio of the main rhythms and cross-correlation connections of the electroencephalography. The revealed changes in the delayed period indicate a pronounced aversive nature of the psychotraumatic effect. CONCLUSIONS: Life-threatening stress is caused by changes in electrophysiological and behavioral parameters in experimental animals not only at the time of exposure, but also in the long-term period.
{"title":"The effect of vital stress on the bioelectric activity of the brain and the behavior of female rats","authors":"T. Avaliani, Nataliya K. Apraksina, S. Tsikunov","doi":"10.17816/maj90520","DOIUrl":"https://doi.org/10.17816/maj90520","url":null,"abstract":"BACKGROUND: Identification of possible biomarkers that assess the severity of post-traumatic stress symptoms is an urgent task for the early diagnosis of post-traumatic stress disorders. The manifestation of emotional states, both human and animal, is reflected in altered behavior and in the violation of the ratio of basic rhythms and cross-correlation connections in the brain electroencephalogram, which indicates the development of pathological processes. \u0000AIM: The aim of the study was to analyze the behavior and electrocorticogram indicators of rats in the delayed period (on day 7) after life-threatening stress, as a way to predict the formation of post-traumatic stress disorder. \u0000MATERIALS AND METHODS: The study was performed on mature female Wistar rats weighing 180200 g (n = 40). Mental trauma was modeled by the circumstances of experiencing the situation of the death of a partner from the action of a predator and the threat to their own life when placing rats in a terrarium with a tiger python. In rats, the behavior in the Open Field test and the bioelectric activity of the brain in the frontal and occipital regions on the left and right were analyzed before and on the 7th day after stress exposure. \u0000RESULTS: It is shown that in the delayed period after vital stress in female rats, there is a decrease in motor and research activity and altered emotional behavior in the Open Field test. Reduction of interhemispheric asymmetry in the index of theta and delta activity and changes in cross-correlation connections in the right hemisphere, as well as changes in the ratio of the main rhythms and cross-correlation connections of the electroencephalography. The revealed changes in the delayed period indicate a pronounced aversive nature of the psychotraumatic effect. \u0000CONCLUSIONS: Life-threatening stress is caused by changes in electrophysiological and behavioral parameters in experimental animals not only at the time of exposure, but also in the long-term period.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131008066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Pigarevsky, S. Maltseva, D. Tanyansky, E. Firova, A. Tatarinov, Natalja V. Chivikova
BACKGROUND: The study sends to quantify type 9 matrix metalloproteinase in serum in patients with coronary heart disease, since this enzyme is able to provoke an immunoinflammatory process leading to destabilization of atherosclerotic plaque, the development of unstable angina and acute coronary syndrome. AIM: Is to conduct a comparative analysis of the quantitative content of MMR-9 in serum in patients with coronary heart disease (CHD) with a different course of angina and atherosclerosis and in relatively healthy individuals. MATERIALS AND METHODS: Blood serum samples of 66 CHD patients were examined. All patients based on clinical examination were divided into 3 groups, depending on the severity of the disease. Quantitative MMR-9 analysis was performed using the Thermo Fisher ELISA kits (BMS2016-2). Determination of the amount of MMR-9 in serum was recorded in the ELX 800 ELISA reader plate. Data processing was carried out using Statistica 6.0 statistical analysis (StatSof, USA). The results were presented as means and mean errors. RESULTS: The obtained results indicate a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of the disease compared to the control group (relatively healthy people). This is probably due to the effect on the content and activity of its MMR-9 inhibitor TIMP-1. Further studies will investigate whether MMR-9 can be considered as a marker of destabilization of atherosclerotic plaque and act as an independent predictor of acute clinical complications in patients with cardiovascular pathology. CONCLUSIONS: The study made it possible to establish a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of atherosclerosis compared to the control group (relatively healthy people). In addition, in patients with an unstable course of atherosclerosis, a tendency to reduce the concentration of this enzyme compared to persons with stable atherosclerosis was revealed.
{"title":"Serum matrix metalloproteinase type 9 in patients with coronary heart disease","authors":"P. Pigarevsky, S. Maltseva, D. Tanyansky, E. Firova, A. Tatarinov, Natalja V. Chivikova","doi":"10.17816/maj104665","DOIUrl":"https://doi.org/10.17816/maj104665","url":null,"abstract":"BACKGROUND: The study sends to quantify type 9 matrix metalloproteinase in serum in patients with coronary heart disease, since this enzyme is able to provoke an immunoinflammatory process leading to destabilization of atherosclerotic plaque, the development of unstable angina and acute coronary syndrome. \u0000AIM: Is to conduct a comparative analysis of the quantitative content of MMR-9 in serum in patients with coronary heart disease (CHD) with a different course of angina and atherosclerosis and in relatively healthy individuals. \u0000MATERIALS AND METHODS: Blood serum samples of 66 CHD patients were examined. All patients based on clinical examination were divided into 3 groups, depending on the severity of the disease. Quantitative MMR-9 analysis was performed using the Thermo Fisher ELISA kits (BMS2016-2). Determination of the amount of MMR-9 in serum was recorded in the ELX 800 ELISA reader plate. Data processing was carried out using Statistica 6.0 statistical analysis (StatSof, USA). The results were presented as means and mean errors. \u0000RESULTS: The obtained results indicate a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of the disease compared to the control group (relatively healthy people). This is probably due to the effect on the content and activity of its MMR-9 inhibitor TIMP-1. Further studies will investigate whether MMR-9 can be considered as a marker of destabilization of atherosclerotic plaque and act as an independent predictor of acute clinical complications in patients with cardiovascular pathology. \u0000CONCLUSIONS: The study made it possible to establish a significant decrease in the concentration of MMR-9 in the serum of patients with an unstable course of atherosclerosis compared to the control group (relatively healthy people). In addition, in patients with an unstable course of atherosclerosis, a tendency to reduce the concentration of this enzyme compared to persons with stable atherosclerosis was revealed.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115497325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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