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4. DNA Methylation Profiles of PSMA6 , PSMB5 , KEAP1 , and HIF1A Genes in Patients with Type 1 Diabetes and Diabetic Retinopathy.

Author

Svikle, Zane, Paramonova, Natalia, Siliņš, Emīls, Pahirko, Leonora, Zariņa, Līga, Baumane, Kristīne, Petrovski, Goran, and Sokolovska, Jelizaveta

Subjects
TYPE 1 diabetes, DNA methylation, DIABETIC retinopathy, GENES, PROMOTERS (Genetics)
Abstract

We explored differences in the DNA methylation statuses of PSMA6, PSMB5, HIF1A, and KEAP1 gene promoter regions in patients with type 1 diabetes and different diabetic retinopathy (DR) stages. Study subjects included individuals with no DR (NDR, n = 41), those with non-proliferative DR (NPDR, n = 27), and individuals with proliferative DR or those who underwent laser photocoagulation (PDR/LPC, n = 46). DNA methylation was determined by Zymo OneStep qMethyl technique. The methylation of PSMA6 (NDR 5.9 (3.9–8.7) %, NPDR 4.5 (3.8–5.7) %, PDR/LPC 6.6 (4.7–10.7) %, p = 0.003) and PSMB5 (NDR 2.2 (1.9–3.7) %, NPDR 2.2 (1.9–3.0) %, PDR/LPC 3.2 (2.5–7.1) %, p < 0.01) differed across the groups. Consistent correlations were observed between the methylation levels of HIF1A and PSMA6 in all study groups. DNA methylation levels of PSMA6, PSMB5, and HIF1A genes were positively correlated with the duration of diabetes, HbA1c, and albuminuria in certain study groups. Univariate regression models revealed a significant association between the methylation level z-scores of PSMA6, PSMB5, and HIF1A and severe DR (PSMA6: OR = 1.96 (1.15; 3.33), p = 0.013; PSMB5: OR = 1.90 (1.14; 3.16), p = 0.013; HIF1A: OR = 3.19 (1.26; 8.06), p = 0.014). PSMB5 remained significantly associated with DR in multivariate analysis. Our findings suggest significant associations between the severity of DR and the DNA methylation levels of the genes PSMA6, PSMB5, and HIF1A, but not KEAP1 gene. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Pharmacokinetics of Glutapyrone and its Impact on Expression of the Genes Involved in DNA Repair and Free Radical Production in Intact and Diabetic Rats

Author

Dišlere, Kristine, Rostoka, Evita, Parinovs, Viktors, Paramonova, Natalia, Bisenieks, Egils, Poikans, Janis, Sokolovska, Jelizaveta, and Sjakste, Nikolajs

Abstract

Modification of expression of several genes encoding enzymes involved in radical production and DNA repair by a 1,4-DHP derivative glutapyrone was studied in intact rats and animals with streptozotocin diabetes mellitus. Glutapyrone stimulated iNosmRNA production in both kidneys and blood. The effect was stronger in kidneys of diabetic animals, however in blood the expression was down-regulated. The compound increased the Parp 1gene expression in kidneys of both intact and diabetic animals; in blood the effect was adverse. Expression of XDhgene was significantly increased by glutapyrone in kidneys of intact and diabetic animals. Administration of the compound to intact animals triggered significant increase of DNA damage in white blood cells assayed by comet assay; in diabetic animals no effect was produced. To explain discrepancies with the formerly described effects of glutapyrone on cultured cells, metabolism of the compound was studied. Glutapyrone is either oxidised or the residue of glutamic acid is removed, glutapyrone turns into AV-153, and the latter is metabolised to smaller compounds. Formation of AV-153, a DNA binder and genotoxic compound in high concentrations, can explain DNA damage in white blood cells and stimulation of DNA repair.

Published
2023
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14. Genome wide analysis of circulating miRNAs in growth hormone secreting pituitary neuroendocrine tumor patients’ plasma

Author

Niedra, Helvijs, primary, Peculis, Raitis, additional, Litvina, Helena Daiga, additional, Megnis, Kaspars, additional, Mandrika, Ilona, additional, Balcere, Inga, additional, Romanovs, Mihails, additional, Steina, Liva, additional, Stukens, Janis, additional, Breiksa, Austra, additional, Nazarovs, Jurijs, additional, Sokolovska, Jelizaveta, additional, Liutkeviciene, Rasa, additional, Vilkevicute, Alvita, additional, Konrade, Ilze, additional, and Rovite, Vita, additional

Published
2022
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18. Telomere Lengths and Serum Proteasome Concentrations in Patients with Type 1 Diabetes and Different Severities of Diabetic Retinopathy in Latvia and Lithuania

Author

Svikle, Zane, primary, Pahirko, Leonora, additional, Zariņa, Līga, additional, Baumane, Kristīne, additional, Kardonaite, Deimante, additional, Radzeviciene, Lina, additional, Daugintyte-Petrusiene, Laura, additional, Balciuniene, Vilma Jurate, additional, Verkauskiene, Rasa, additional, Tiščuka, Angeļina, additional, Rovite, Vita, additional, Sjakste, Nikolajs, additional, and Sokolovska, Jelizaveta, additional

Published
2022
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23. Additional file 1 of Quantitative and qualitative analysis of the quality of life of Type 1 diabetes patients using insulin pumps and of those receiving multiple daily insulin injections

Author

Tzivian, Lilian, Sokolovska, Jelizaveta, Grike, Anna E., Kalcenaua, Agate, Seidmann, Abraham, Benis, Arriel, Mednis, Martins, Danovska, Ieva, Berzins, Ugis, Bogdanovs, Arnolds, and Syundyukov, Emil

Abstract

Additional file 1. Surveys by blocks, qualitative responses of participants, supplemental tables and figures.

Published
2022
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25. Quantitative And Qualitative Analysis Of The Quality Of Life Of Type 1 Diabetes Patients Using Insulin Pumps And Of Those Receiving Multiple Daily Insulin Injections

Author

Tzivian, Lilian, primary, Sokolovska, Jelizaveta, additional, Grike, Anna E, additional, Kalcenaua, Agate, additional, Seidmann, Abraham, additional, Benis, Arriel, additional, Mednis, Martins, additional, Danovska, Ieva, additional, Berzins, Ugis, additional, Bogdanovs, Arnolds, additional, and Syundyukov, Emil, additional

Published
2022
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29. Association between diabetic retinopathy, telomere length and serum proteasome concentration in type 1 diabetes: cross-sectional study in Latvia and Lithuania

Author

Svikle, Zane, primary, Tiscuka, Angelina, additional, Voitovica, Liga, additional, Pahirko, Leonora, additional, Baumane, Kristine, additional, Kardonaite, Deimante, additional, Kazokaite, Mintaute, additional, Lina, Radzeviciene@yahoo.com, additional, Laura, Daugintyte-Petrusiene, additional, Balciuniene, Jurate, additional, and Sokolovska, Jelizaveta, additional

Published
2021
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32. Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue

Author

Saksis, Rihards, primary, Silamikelis, Ivars, additional, Laksa, Pola, additional, Megnis, Kaspars, additional, Peculis, Raitis, additional, Mandrika, Ilona, additional, Rogoza, Olesja, additional, Petrovska, Ramona, additional, Balcere, Inga, additional, Konrade, Ilze, additional, Steina, Liva, additional, Stukens, Janis, additional, Breiksa, Austra, additional, Nazarovs, Jurijs, additional, Sokolovska, Jelizaveta, additional, Pirags, Valdis, additional, Klovins, Janis, additional, and Rovite, Vita, additional

Published
2021
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35. Baseline gut microbiome composition predicts metformin therapy short-term efficacy in newly diagnosed type 2 diabetes patients

Author

Elbere, Ilze, primary, Silamikelis, Ivars, additional, Dindune, Ilze Izabella, additional, Kalnina, Ineta, additional, Ustinova, Monta, additional, Zaharenko, Linda, additional, Silamikele, Laila, additional, Rovite, Vita, additional, Gudra, Dita, additional, Konrade, Ilze, additional, Sokolovska, Jelizaveta, additional, Pirags, Valdis, additional, and Klovins, Janis, additional

Published
2020
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37. Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response

Author

Ustinova, Monta, primary, Ansone, Laura, additional, Silamikelis, Ivars, additional, Rovite, Vita, additional, Elbere, Ilze, additional, Silamikele, Laila, additional, Kalnina, Ineta, additional, Fridmanis, Davids, additional, Sokolovska, Jelizaveta, additional, Konrade, Ilze, additional, Pirags, Valdis, additional, and Klovins, Janis, additional

Published
2020
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38. Impact of interval walking training managed through smart mobile devices on albuminuria and leptin/adiponectin ratio in patients with type 2 diabetes

Author

Sokolovska, Jelizaveta, primary, Ostrovska, Karina, additional, Pahirko, Leonora, additional, Varblane, Gunita, additional, Krilatiha, Ksenija, additional, Cirulnieks, Austris, additional, Folkmane, Inese, additional, Pirags, Valdis, additional, Valeinis, Janis, additional, Klavina, Aija, additional, and Selavo, Leo, additional

Published
2020
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49. Overproduction of nitric oxide in animals with streptozotocin diabetes mellitus is down-regulated by dihydropiridines

Author

Nikolajs Sjakste, Duburs Gunars, Bisenieks Egils, Baumane Larisa, and Sokolovska Jelizaveta

Subjects
Cancer Research, medicine.medical_specialty, Physiology, business.industry, Clinical Biochemistry, Adipose tissue, DHPS, Disease, medicine.disease, Streptozotocin, Biochemistry, Nitric oxide, chemistry.chemical_compound, Endocrinology, chemistry, Diabetes mellitus, Internal medicine, Medicine, Channel blocker, business, Overproduction, medicine.drug
Abstract

Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic action of nitric oxide (NO) is responsible to a large extent for development of complications of the disease. Thus search for compounds modifying NO production in DM patients appears to be important for development of pharmacological remedies for treatment of DM complications. Dihydropiridines (DHP) appear to be prospective compounds from this point of view. The goal of the present work was to study alterations of NO production in streptozotocin model of DM in rats and ability of several DHPs and to normalize NO synthesis. Production of nitric oxide was monitored by means of ESP spectroscopy of Fe–DETC–NO complex. Development of streptozotocin diabetes was followed by increase of NO production in the liver, kidneys, blood and muscles. In adipose tissue changes in NO production were adverse. Cerebrocrast treatment (0.5 mg/kg per os for 3 days) was followed by normalization of NO production in the liver, kidneys and blood. Another DHP etaftoron administered in similar dose was effective in kidneys, blood and muscles. Fenaftoron decreased NO production in the liver of diabetic animals and also kidneys, blood and muscles. Elucidation of the DHP action site in the mechanism of the NO production will be the goal of our future studies. As the studied DHP are Ca 2+ channel blockers constitutive NO synthases seem to be most the likely candidates for targets of these drugs. The work was supported by the Program 2010.10.-4/VPP4 and ERAF Project No. 2010/0202/2DP/2.1.1.2.0/10/APIA/VIAA/013.

Published
2012

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