5 research outputs found
Role Of Retroelements In The Development Of COVID-19 Neurological Consequences
Retroelements play a key role in brain functioning in humans and other animals, since they represent dynamic regulatory elements controlling the expression of specific neuron types. The activity of retroelements in the brain is impaired under the influence of SARS-CoV-2, penetrating the blood-brain barrier. We propose a new concept, according to which the neurological complications of COVID-19 and their long-term effects are caused by modified expression of retroelements in neurons due to viral effect. This effect is implemented in several ways: a direct effect of the virus on the promoter regions of retroelement-encoding genes, virus interaction with miRNAs causing silencing of transposons, and an effect of the viral RNA on the products of retroelement transcription. Aging-related physiological activation of retroelements in the elderly is responsible for more severe course of COVID-19. The associations of multiple sclerosis, Parkinsonβs disease, Guillain-BarrΓ© syndrome, acute disseminated encephalomyelitis with coronavirus lesions also indicate the role of retroelements in such complications, because retroelements are involved in the mechanisms of the development of these diseases. According to meta-analyses, COVID-19-caused neurological complications ranged 36.4-73%. The neuropsychiatric consequences of COVID-19 are observed in patients over a long period after recovery, and their prevalence may exceed those during the acute phase of the disease. Even 12 months after recovery, unmotivated fatigue, headache, mental disorders, and neurocognitive impairment were observed in 82%, 60%, 26.2-45%, and 16.2-46.8% of patients, correspondingly. These manifestations are explained by the role of retroelements in the integration of SARS-CoV-2 into the human genome using their reverse transcriptase and endonuclease, which results in a long-term viral persistence. The research on the role of specific retroelements in these changes can become the basis for developing targeted therapy for neurological consequences of COVID-19 using miRNAs, since epigenetic changes in the functioning of the genome in neurons, affected by transposons, are reversible
ΠΠΠΠΠΠΠΠ’ΠΠΠ ΠΠΠΠ¦ΠΠ ΠΠΠΠΠΠΠ
Currently, the key mechanisms of carcinogenesis are epigenetic events. Epigenetic factors include DNA methylation, histone modifications, microRNA expression and higher chromatin organization. Non-coding RNAs include microRNAs, small interfering RNAs or siRNAs, piRNAs, long noncoding RNAs or lncRNAs. According to recent data, most of these RNAs are directly formed from mobile genetic elements or have a transposon origin. Non-coding RNAs specifically affect the methylation of the genome and the modification of histones in ontogenesis. This is facilitated by evolutionarily programmed features of activation of transposons, since non-coding RNAs are formed from transposons. Thus, the material basis of epigenetic heredity are the transposons. Stress and aging increase the likelihood of developing cancer. This can be explained by an increase in the number of abnormal activation of mobile genetic elements that are sensitive to stress and hormones. Abnormal activation of transposons in cells leads to genomic instability-most such cells undergo apoptosis. However, in some cases, progressive genomic instability leads to damage to oncospressor genes and oncogenes activation - as a result of apoptosis does not occur, and cells acquire the ability of uncontrolled proliferation with the accumulation of a variety of mutations due to the progressive genomic instability caused by the mobilization of transposons. In each type of malignant tumors, specific cascade mechanisms of activation of mobile genetic elements with the participation of non-coding RNA are triggered. The study of epigenetic mechanisms of development of each type of cancer will enable to develop effective methods for early molecular genetic diagnosis of cancer, as well as targeted therapy at different stages of carcinogenesis.Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΊΠ»ΡΡΠ΅Π²ΡΠΌΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ ΠΊΠ°Π½ΡΠ΅ΡΠΎΠ³Π΅Π½Π΅Π·Π° ΠΏΡΠΈΠ·Π½Π°Π½Ρ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΎΠ±ΡΡΠΈΡ, ΠΊ ΠΊΠΎΡΠΎΡΡΠΌ ΠΎΡΠ½ΠΎΡΡΡΡΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΠΠ, ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ Π³ΠΈΡΡΠΎΠ½ΠΎΠ², ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ Π²ΡΡΡΠ°Ρ Ρ
ΡΠΎΠΌΠ°ΡΠΈΠ½ΠΎΠ²Π°Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΡ. Π‘ΠΎΠ³Π»Π°ΡΠ½ΠΎ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠΌ Π΄Π°Π½Π½ΡΠΌ, Π½Π΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΠ΅ Π ΠΠ (ΠΌΠΈΠΊΡΠΎΠ ΠΠ, ΠΌΠ°Π»ΡΠ΅ ΠΈΠ½ΡΠ΅ΡΡΠ΅ΡΠΈΡΡΡΡΠΈΠ΅ Π ΠΠ ΠΈΠ»ΠΈ siΠ ΠΠ, piΠ ΠΠ, Π΄Π»ΠΈΠ½Π½ΡΠ΅ Π½Π΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΠ΅ Π ΠΠ ΠΈΠ»ΠΈ lncΠ ΠΠ) Π² Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΡΠ²ΠΎΠ΅ΠΌ Π»ΠΈΠ±ΠΎ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎ ΠΎΠ±ΡΠ°Π·ΡΡΡΡΡ ΠΈΠ· ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², Π»ΠΈΠ±ΠΎ ΠΈΠΌΠ΅ΡΡ ΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Π½ΠΎΠ΅ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅. ΠΠ΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΠ΅ Π ΠΠ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ Π²Π»ΠΈΡΡΡ Π½Π° ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠΌΠ° ΠΈ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ Π³ΠΈΡΡΠΎΠ½ΠΎΠ² Π² ΠΎΠ½ΡΠΎΠ³Π΅Π½Π΅Π·Π΅, ΡΠ΅ΠΌΡ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΡΡ ΡΠ²ΠΎΠ»ΡΡΠΈΠΎΠ½Π½ΠΎ Π·Π°ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ², ΠΈΠ· ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΊΠΎΡΠΎΡΡΡ
ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΡΡ Π΄Π°Π½Π½ΡΠ΅ Π ΠΠ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΎΡΠ½ΠΎΠ²ΠΎΠΉ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ»ΡΠΆΠ°Ρ ΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½Ρ. ΠΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΡΡΡΠ΅ΡΡΠ° ΠΈ ΠΏΡΠΈ ΡΡΠ°ΡΠ΅Π½ΠΈΠΈ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅ΡΡΡ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ, ΡΡΠΎ ΠΎΠ±ΡΡΡΠ½ΡΠ΅ΡΡΡ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡΡ Π°Π½ΠΎΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΊ ΡΡΡΠ΅ΡΡΠΎΠ²ΡΠΌ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡΠΌ ΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΡΠΎΠ²Π½Ρ Π³ΠΎΡΠΌΠΎΠ½ΠΎΠ². ΠΠ½ΠΎΠΌΠ°Π»ΡΠ½Π°Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ² Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π²Π΅Π΄Π΅Ρ ΠΊ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠΉ Π½Π΅ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ β Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°ΡΡΡΡ Π°ΠΏΠΎΠΏΡΠΎΠ·Ρ. ΠΠ΄Π½Π°ΠΊΠΎ Π² Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΡΠ»ΡΡΠ°ΡΡ
ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ°Ρ Π³Π΅Π½ΠΎΠΌΠ½Π°Ρ Π½Π΅ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΡ Π²Π΅Π΄Π΅Ρ ΠΊ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠΎΠ² ΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΎΠ½ΠΊΠΎΠ³Π΅Π½ΠΎΠ² - Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ Π°ΠΏΠΎΠΏΡΠΎΠ·Π° Π½Π΅ ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΠΈΡ, Π° ΠΊΠ»Π΅ΡΠΊΠΈ ΠΎΠ±ΡΠ΅ΡΠ°ΡΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ Π½Π΅ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΡΡΠ΅ΠΉ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ Ρ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ΠΌ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° ΠΌΡΡΠ°ΡΠΈΠΉ Π²ΡΠ»Π΅Π΄ΡΡΠ²ΠΈΠ΅ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΡΡΡΠ΅ΠΉ Π³Π΅Π½ΠΎΠΌΠ½ΠΎΠΉ Π½Π΅ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ, Π²ΡΠ·Π²Π°Π½Π½ΠΎΠΉ ΠΌΠΎΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ ΡΡΠ°Π½ΡΠΏΠΎΠ·ΠΎΠ½ΠΎΠ². Π ΠΊΠ°ΠΆΠ΄ΠΎΠΌ ΡΠΈΠΏΠ΅ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Π·Π°ΠΏΡΡΠΊΠ°ΡΡΡΡ ΡΠ²ΠΎΠΈ ΠΊΠ°ΡΠΊΠ°Π΄Π½ΡΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΌΠΎΠ±ΠΈΠ»ΡΠ½ΡΡ
Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ Π½Π΅ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΡ
Π ΠΠ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ ΡΠΈΠΏΠ° ΡΠ°ΠΊΠ° Π΄Π°ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΡΠ°Π½Π½Π΅ΠΉ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΎΠ½ΠΊΠΎΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠ°ΡΠ³Π΅ΡΠ½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π½Π° ΡΠ°Π·Π½ΡΡ
ΡΡΠ°Π΄ΠΈΡΡ
ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ°
EPIGENETICS OF CARCINOGENESIS
Currently, the key mechanisms of carcinogenesis are epigenetic events. Epigenetic factors include DNA methylation, histone modifications, microRNA expression and higher chromatin organization. Non-coding RNAs include microRNAs, small interfering RNAs or siRNAs, piRNAs, long noncoding RNAs or lncRNAs. According to recent data, most of these RNAs are directly formed from mobile genetic elements or have a transposon origin. Non-coding RNAs specifically affect the methylation of the genome and the modification of histones in ontogenesis. This is facilitated by evolutionarily programmed features of activation of transposons, since non-coding RNAs are formed from transposons. Thus, the material basis of epigenetic heredity are the transposons. Stress and aging increase the likelihood of developing cancer. This can be explained by an increase in the number of abnormal activation of mobile genetic elements that are sensitive to stress and hormones. Abnormal activation of transposons in cells leads to genomic instability-most such cells undergo apoptosis. However, in some cases, progressive genomic instability leads to damage to oncospressor genes and oncogenes activation - as a result of apoptosis does not occur, and cells acquire the ability of uncontrolled proliferation with the accumulation of a variety of mutations due to the progressive genomic instability caused by the mobilization of transposons. In each type of malignant tumors, specific cascade mechanisms of activation of mobile genetic elements with the participation of non-coding RNA are triggered. The study of epigenetic mechanisms of development of each type of cancer will enable to develop effective methods for early molecular genetic diagnosis of cancer, as well as targeted therapy at different stages of carcinogenesis
Genetic Polymorphisms of Cytochromes P450 in Finno-Permic Populations of Russia
Cytochrome P450 is an enzyme involved in the metabolism of phase 1 xenobiotics, toxins, endogenous hormones, and drugs, including those used in COVID-19 treatment. Cytochrome p450 genes are linked to the pathogenesis of some multifactorial traits and diseases, such as cancer, particularly prostate cancer, colorectal cancer, breast cancer, and cervical cancer. Genotyping was performed on 540 supposedly healthy individuals of 5 Finno-Permic populations from the territories of the European part of the Russian Federation. There was a statistically significant difference between Veps and most of the studied populations in the rs4986774 locus of the CYP2D6 gene; data on the rs3892097 locus of the CYP2D6 gene shows that Izhemsky Komis are different from the Mordovian and Udmurt populations
Host Genetic Variants Linked to COVID-19 Neurological Complications and Susceptibility in Young AdultsβA Preliminary Analysis
To date, multiple efforts have been made to use genome-wide association studies (GWAS) to untangle the genetic basis for SARS-CoV-2 infection susceptibility and severe COVID-19. However, data on the genetic-related effects of SARS-CoV-2 infection on the presence of accompanying and long-term post-COVID-19 neurological symptoms in younger individuals remain absent. We aimed to examine the possible association between SNPs found in a GWAS of COVID-19 outcomes and three phenotypes: SARS-CoV-2 infection, neurological complications during disease progression, and long-term neurological complications in young adults with a mild-to-moderate disease course. University students (N = 336, age 18β25 years, European ancestry) with or without COVID-19 and neurological symptoms in anamnesis comprised the study sample. Logistic regression was performed with COVID-19-related phenotypes as outcomes, and the top 25 SNPs from GWAS meta-analyses and an MR study linking COVID-19 and cognitive deficits were found. We replicated previously reported associations of the FURIN and SLC6A20 gene variants (OR = 2.36, 95% CI 1.31β4.24) and OR = 1.94, 95% CI 1.08β3.49, respectively) and remaining neurological complications (OR = 2.12, 95% CI 1.10β4.35 for SLC6A20), while NR1H2 (OR = 2.99, 95% CI 1.39β6.69) and TMPRSS2 (OR = 2.03, 95% CI 1.19β3.50) SNPs were associated with neurological symptoms accompanying COVID-19. Our findings indicate that genetic variants related to a severe COVID-19 course in adults may contribute to the occurrence of neurological repercussions in individuals at a young age