Type Of Acetylation Research Articles

Прогнозування післяопераційної спайкової кишкової непрохідності та її рецидиву в дітей

It is known that the expressiveness of the adhesion process (AP) depends on the individual characteristics of the connective tissue metabolism. In recent years, the role of acetylation processes in predicting pathological adhesion formation has been actively studied. A genetically determined fast type of acetylation is an unfavorable background for the development of peritoneal adhesion disease (PAD). Aim - to study the effectiveness of predicting postoperative adhesive intestinal obstruction (AIO) and its recurrence in children based on determining the acetylation phenotype (APh). Materials and methods. In order to reveal the prognostic value of the acetylation phenotype in the formation of postoperative (AIO), we studied the activity of acetylation in 30 children aged 4-16 years, operated on for appendicular peritonitis (the main group). The control group consisted of 30 somatically healthy children. In addition, a study of APh was conducted in 42 children aged 3-17 years, who underwent surgery for postoperative AIO, to study the informativeness of this test as a prognostic factor for AIO recurrence. APh was established in children by determining the biochemical activity of the enzyme N-acetyltransferase (NAT). Results. It was established that in children operated on for appendicular peritonitis, in which postoperative AIO occurred, rapid acetylation phenotype (RAP) prevailed (57.14% of children), and in children without signs of AIO, RAP was detected in only one case (6.25%). Among the children operated on for postoperative AIO, the proportion of patients with RAP was even higher (63.64%). Opposite results were noted regarding slow acetylation phenotype (SAP). Among children with recurrent AIO, RAP was detected in 57.14% of cases, and among patients without relapse RAP was diagnosed in 25.0% of children. The opposite pattern was observed in patients with SAP. A direct correlative relationship between NAT activity and the value of the peritoneal adhesion index (PAI) was noted - the higher level of NAT activity, the higher PAI. Conclusions. Determination of APh in children based on the biochemical activity of the NAT enzyme allows to establish the degree of risk of AIO. AIO and its recurrence are significantly more common in patients with RAP. Detection of RAP in a patient can serve as a prognostic criterion for the severity of AP. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of all institutions mentioned in the work. Informed consent of the women was obtained for the research. The authors declare no conflict of interest.

Associations of polymorphisms of glutathione-S-transferase and N-acetyltransferase 2 genes in children with acute lymphoblastic leukemia

The development of personalized medicine is inextricably linked with the study of the patient’s genetic profile, which determines not only the features of the course of the disease, but also the risks of its occurrence. Purpose. The aim of the work was to study possible associations between the genetic polymorphisms GSTT1, GSTM1, NAT2 and predisposition to the development of acute lymphoblastic leukemia in children of the East Siberian region. Material and methods. A total of 82 children with acute lymphoblastic leukemia and 227 healthy volunteers with no history of hematological pathology were examined. Deletion polymorphisms in the glutathione S-transferase GSTT1 and GSTM1 genes were detected by polymerase chain reaction (PCR) with electrophoretic detection of amplification products in agarose gel; the type of acetylation was determined by genotyping SNP rs1495741 of the NAT2 gene by conducting a polymerase chain reaction in real time. The material for the study was DNA samples isolated from buccal epithelium samples. Results. Statistical processing allowed us to draw the following conclusions: the rate of acetylation of xenobiotics does not affect the risk of acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region. Conclusion. There is no associative relationship between deletions in the GSTM1 and GSTT1 genes and the risk of developing acute lymphoblastic leukemia in children of the Caucasian ethnic group of the East Siberian region. It was found that the risk of developing acute lymphoblastic leukemia in children was significantly higher with the variant of combinations of alleles of the rapid type of NAT2 acetylation and normal activity of GSST1 and GSTM1 (G/G, active, active).

Assessment Of The Process Of Acetylation And Lipid Composition Of Blood In Patients With Chronic Periodontitis Against The Background Of Viral Hepatitis C

The purpose of this study was to study the relationship between alel variants of acetylation and the lipid composition of blood in patients with chronic periodontitis against the background of viral hepatitis C. Biochemical studies were carried out in 42 people aged 18-45 years (24 men and 18 women) diagnosed with chronic periodontitis against the background of chronic hepatitis C. The phenotype of acetylation in saliva and the lipid spectrum of blood were studied. The prevalence of the disease among patients with slow type of acetylation in saliva was noted at an average of 17% in the examined patients of the study group. In patients with slow type of acetylation, a high level of triglycerides was noted, which was accompanied by a low concentration of cholesterol, high and low density lipoproteins in the blood

Прогнозування ризику розвитку післяопераційної злукової кишкової непрохідності в дітей

Прогнозування ризику розвитку післяопераційної злукової кишкової непрохідності в дітей

The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease

Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (K_hib) is a novel type of acetylation. In this study, we aimed to reveal the key features of K_hib in peripheral blood monocytes (PBMCs) of patients with ESRD. Method: We combined TMT labeling with LC-MS/MS analysis to compare K_hib modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of K_hib, and the bioinformatics analysis was conducted to analyze the pathology of these K_hib-modified proteins. Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 K_hib sites on 324 upregulated proteins and 287 K_hib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the K_hib protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients. Conclusion: In this study, we found that K_hib-modified proteins correlated with the occurrence and progression of ESRD.

Study of the Effect of Polymorphic Markers of the NAT2 Gene on the Risk of Adverse Drug Reactions in Patients with Pulmonary Tuberculosis Who Received Isoniazid and Rifampicin

Tuberculosis remains one of the most dangerous and widespread infectious diseases. More than 20 medicinal products are currently available for the treatment of tuberculosis. One of the most serious adverse drug reactions (ADRs) associated with anti-tuberculosis medicines is hepatotoxicity.The aim of the study was to assess the effect of polymorphic markers of the NAT2 gene on the ADR risk in patients with pulmonary tuberculosis who received isoniazid and rifampicin.Materials and methods. The study included 67 patients with different forms of pulmonary tuberculosis who received combination therapy with isoniazid and rifampicin. Single nucleotide polymorphisms (SNPs) of the NAT2 gene were determined by real-time PCR. Statistical processing was performed using SPSS Statistics 20.0.Results: Six SNPs were identified in the NAT2 gene. Based on these SNPs the following phenotypes were determined by the rate of NAT2 acetylation: fast acetylators—6 subjects, intermediate acetylators—24 subjects, and slow acetylators—37 subjects. The study assessed the relationship between the acetylator phenotype and the development of ADRs during combination therapy with isoniazid and rifampicin. Slow acetylators had a significantly greater increase in total bilirubin level (p=0.011) compared to intermediate acetylators. Loss of appetite was more often observed in fast acetylators than in intermediate acetylators (p=0.021).Conclusions. The obtained data suggest interrelation between the slow type of NAT2 acetylation and the risk of ADRs in patients undergoing pulmonary tuberculosis chemotherapy with isoniazid and rifampicin. Out of all the ADRs registered in the study, the fast acetylators were more likely to have loss of appetite, however, the expansion of the study population is needed to verify this observation. The studied polymorphisms have an impact on the development of ADRs in patients undergoing pulmonary tuberculosis chemotherapy with isoniazid and rifampicin and may be used to predict the safety profile of pharmacotherapy in this group of patients.

Systems Biology and Multi‐Omics

Systems Biology and Multi‐Omics

Peculiarities of water-electrolytic metabolism of rats with “slow” type of acetylation after a combined effect of cadmium chloride and sodium nitrate

Peculiarities of water-electrolytic metabolism of rats with “slow” type of acetylation after a combined effect of cadmium chloride and sodium nitrate

Functional renal state of mature rats with a quick type of acetylation under conditions of cadmium chloride and sodium nitrate

Functional renal state of mature rats with a quick type of acetylation under conditions of cadmium chloride and sodium nitrate

Optimization of personalized approaches to the basic treatment of persistent bronchial asthma in children regarding the phenotypic and genotypic characteristics of patients

Objective. To evaluate the effectiveness of inhaled glucocorticosteroids in children with atopic and non-atopic asthma phenotypes depending on the acetylation status.Material and methods. A complex clinico-immunological examination involved 119 children with bronchial asthma. The genetic marker, namely the type of acetylation, has been identified by the method of V. M. Prebsting — V. I. Gavrilova in the modification of Timofeeva. They were divided into four clinical groups: group I — 36 children with atopic bronchial asthma (ABA) and slow acetylation type (patients’ average age — 13,4±0,6 years, the proportion of boys — 69,2±2,2%), group II — 30 patients with fast acetylating status and ABA (average age of patients — 12,±0,5 years, the quota of boys — 70,0±2,0%). The third (III) clinical group included 26 patients with nonatopic variant of the disease and slow acetylation phenotype (patients’ average age — 12,6±0,6 years, the proportion of boys — 59,1±1,6%), and in the forth (ІV) group there were 26 patients with nonatopic bronchial asthma (NBA) with a fast typeof acetylation (average age of patients — 12,5±0,6 years; (P> 0,05); the share of boys - 65,2±2,0% (P> 0,05). The main clinical characteristics of the comparison groups were comparable.Results. The use of IGS in patients with a fast acetylation status and atopic bronchial asthma were found to be more effective than that in patients with slow acetylation type, and such treatment improved clinical and paraclinical parameters of asthma control significantly as evidenced by an increase in the relative risk of a relatively satisfactory level of control by 68.1%, an increase in the absolute risk of bronchial asthma control by 58.0%, with a minimum number of patients who need to be treated by such method in order to achieve at least one positive result is 2.2. At the same time, in patients with a non-atopic bronchial asthma phenotype in the presence of a slow acetylation status, the use of IGS resulted in an increase by 59.7% of relative risk by 47.0% of absolute risk of control of the disease. Conclusions. Basic anti-inflammatory therapy of bronchial asthma using ICS is more effective for treatment of children with atopic asthma as well as for patients with nonatopic asthma phenotype associated with a slow type of acetylation.

МЕТОДЫ ДИАГНОСТИКИ ПОСЛЕОПЕРАЦИОННОГО СПАЕЧНОГО ПРОЦЕССА В МАЛОМ ТАЗУ У ЖЕНЩИН С ХРОНИЧЕСКОЙ ТАЗОВОЙ БОЛЬЮ НА ФОНЕ НЕДИФФЕРЕНЦИРОВАННОЙ ДИСПЛАЗИИ СОЕДИНИТЕЛЬНОЙ ТКАНИ

Objective: To optimize the diagnostic accuracy of the postoperative adhesion process on the background of undifferentiated connective tissue dysplasia (UCTD) in patients with chronic pelvic pain Methods: The study conducted based on the Regional Clinical Hospital "Regional Clinical Perinatal Center", during which 60 patients diagnosed with tubal and peritoneal infertility. Patients divided into 2 groups based on a modified scoring scale of T. I. Kadurina. A study of genotype-phenotypic predictors carried out by analyzing the expression of UCTD by the method of profiling phenotypic markers, according to a modified scale of T.I. Kadurina. The study of polymorphism of VEGF 634 [rs2010963], IL6-174 [rs1800795] genes, and the evaluation of the adhesion process according to the classification system of the American Fertility Society, the genetic predisposition to the development of the adhesion process by the method of genotyping acetylation and pain intensity on a visual analogue scale. Results: Patients with the grade of UCTD scores equal to 10 or more according to the modified scale of T.I. Kadurina assigned to the high-risk group for pelvic peritoneal adhesions (PPA). Diagnosis of predisposition to adhesions by methods of determining the type of acetylation and ultrasound suggests the presence of adhesions in the small pelvis before surgery in 76.66% and 65% of those examined respectively. The molecular-genetic predictors of UCTD are C/C IL6-174 allele C and C/G VEGFA 634 allele G. The intensity of chronic pelvic pain in the adhesive process depends on the stage of the latter. To predict the risk of development of PPA, the developed mathematical model based on P = 1/(1+еЂ(–z)) and independent predictors should be used: myopia, mitral valve prolapse, IL6-174 [rs1800795], VEGFA 634 [rs2010963] and phenotype of acetylation. Conclusion: Using the method of binary logistic regression on the basis of clinical, anamnestic, experimental and molecular-genetic data makes it possible to determine the probability of development of PPA on the background of UCTD using the formula: P = 1/(1+еЂ(–z)). Keywords: Pelvic peritoneal adhesions, chronic pelvic pain, acetylation, binary logistic regression

The effect of acetylation phenotype on the dynamic changes of indices of calcium metabolism and iron levels in liver detoxification on the background of experimental hypothyroidism

Background: Some studies of the characteristics of the calcium-phosphorus metabolism changes in experimental hypothyroidism given the phenotype of acetylation will allow to more effectively diagnose, predict the course and to carry out prevention and treatment of hypothyroidism and the accompanying pathological changes.The aim is to trace the dynamics of phosphorus-calcium metabolism and the level of serum iron in experimental hypothyroidism and to determine the severity of it changes depending on the type of acetylation.Methods: In experiments were used rats weighing 180-220g, who were divided into 2 main groups depending on the type of acetylation on α - slow and β - fast metabolizer (acetylators). Each group was modelled experimental hypothyroidism by the introduction of mercazolil at a dose of 5 mg, for 14 days. Each group was divided into 5 subgroups depending on the time of the study. Group of α-slow metabolizers (acetylators) were divided into the following subgroups: Iα - intact IIα - at the 4th hour of the study, IIIα - on the 1st week of the study, IVα - 2-week studies, Vα - on the 3rd week of the study.Results: In the study of the calcium concentration at the 4th hour of the study in subgroups with α - and β - acetylation phenotypes were observed the decrease by 12.0% and 10.5% respectively, and its level in the IIβ - subgroup was 5.3% lower than the IIα- subgroup. The concentration of calcium ions in Vα subgroup was lower than in the Iα sub-group was 12.0%, and the level of calcium in the blood serum of animals Vβ was lower compared to Iβ IIβ IIIβ Ivβ-90.9%, 72.7%, 80.0%, 80.9% respectively. Also relatively, Vα Vβ subgroups in the subgroup calcium concentration were lower at 81.8 percent.Conclusions: Belonging to a particular phenotype of acetylation affects the degree of severity of the changes of indices of calcium-phosphorus metabolism and serum iron in experimental hypothyroidism, the most significant differences between the values of their indicators were detected early and deadlines of the study.

Effectiveness of desobstructive therapy of atopic asthma in schoolchildren

To increase the efficiency of medical measures in acute period of atopic asthma in schoolchildren based on the evaluation of the peculiarities of desobstructive therapy two groups were formed for clinical observation. The first clinical group included 48 schoolchildren suffering from atopic asthma, the comparison group comprised 26 peers with nonatopic asthma. The study shows that the proportion of children who received systemic corticosteroids was slightly higher in atopic phenotype than in the comparison group. Absolute risk reduction (ARR) of systemic corticosteroids use in patients with the fast type of acetylation relatively to "slow" acetylators was 12.0 %; relative risk reduction (RRR) was 16.0 %, the number of patients to be treated to gain the positive result (NPBT) was 8.3. ARR of corticosteroids use in patients with genotype T1+ M1+ relatively to children with polymorphism of these genes was 6.8 %, RRR was 8.3% and NPBT was 14.7 %.

Transcriptional signatures mediated by acetylation overlap with early-stage Alzheimer’s disease

The mechanisms by which environmental influences lead to the development of complex neurodegenerative diseases are largely unknown. It is known, however, that epigenetic mechanisms can mediate alterations in transcription due to environmental influences. In order to identify genes susceptible to regulation in the adult cortex by one type of epigenetic mechanism, histone, and protein acetylation, we treated mice with the histone deacetylase inhibitor Trichostatin A (TSA). After 1week of treatment with TSA, RNA was extracted from the brain cortices of mice and gene expression differences were analyzed by microarray profiling. The altered genes were then compared with genes differentially expressed in microarray studies of disease by database and literature searches. Genes regulated by TSA were found to significantly overlap with differentially expressed genes in the Alzheimer's disease (AD) brain. Several TSA-regulated genes involved in chromatin remodeling and epigenetic reprogramming including histone cluster 1, H4h (Hist1H4h), methionine adenosyltransferase II, alpha (Mat2a), and 5-methyltetrahydrofolate homocysteine reductase (Mtrr) overlapped with genes altered in early-stage AD in gray matter. We also show that the expression of hemoglobin, which has been shown to be altered in neurons in the AD brain, is regulated by TSA treatment. This analysis suggests involvement of epigenetic mechanisms in neurons in early stages of AD.

Type of acetylation as susceptibility biomarker of imidacloprid, dimethoat and sodium nitrate exposure

Type of acetylation as susceptibility biomarker of imidacloprid, dimethoat and sodium nitrate exposure

Facets of Histone Acetylation Required for Light-Responsive Gene Expression

Histone acetylation is an important componentofchromatin structurethataffectsgene transcription. Hyperacetylation of histones relaxes chromatin structure and is associated with transcriptional activation, whereas hypoacetylation of histones induces chromatin compaction and gene repression. Benhamed et al. (pages 2893–2903) present new information on the effects ofhistone acetylation of chromatin on light-regulated gene expression. This work firmly establishes the pivotal role of Arabidopsis GCN5 and HD1 in controlling histone acetylation levels over several light-responsive genes and makes an important contribution to our understanding oftheroleplayedbychromatin in regulating gene expression. It was previously found that the histone acetyltransferase TAF1 is required for light regulation of gene expression. In this work, the authors show that histone acetyltransferase GCN5andhistonedeacetylaseHD1arealso involved and play opposing roles that may help tofine-tuneand balancelight regulation of gene expression. Mutations of GCN5 resulted in a long hypocotyl phenotype and reduced light-induced gene expression, whereas mutations in HD1 had the opposite effect. The authors further characterize the extent and type of histone acetylation on target promoters and find that TAF1, GCN5, andHD1havedistinctandspecificeffectson histone acetylation required for light regulation of gene expression.

Spectrophotometric and chromatographic determination of sulfanilamides in biological fluids and pharmaceuticals

The conditions for the determination of norsulfazol (I), sulfadimezine (II), ethazole (III), sulfamethoxypyridazine (IV), sulfadimethoxine (V), sodium sulfacyl (VI), sulfalene (VII), sulgin (VIII), and bucarban (IX) as their derivatives of 4,6-dinitrobenzofuroxan using spectrophotometry and thin-layer chromatography were selected. The best results were obtained at 490–500 nm using polar solvents and their aqueous mixtures of pH 6.68 as analytical media. The analytical range for sulfanilamides was 0.5–6.0 Μg/mL. The limits of detection (Μg/mL) were 0.24 for 1,0.28 for II, 0.43 for III, 0.18 for IV, 0.25 for V, 0.54 for VI, 0.54 for VII, 0.17 for VII, and 0.31 for IX. Sulfanilamides were determined in Pharmaceuticals (tablets, ointments, and drops) and biological fluids (protein hydrolyzates, urine, blood serum, and whole blood). A simple rapid method for the determination of the phenotype of biotransformation by the type of acetylation was developed based on the studies of the kinetics of the excretion of II from the human body with urine.