Specific gene expression in type 1 diabetic patients with and without cardiac autonomic neuropathy

Abstract

transduction 11. The induction of gp130 family of cytokines parallel axonal injury, in the experimentally induced diabetic mice, significantly decreased axonal regeneration 12. This study's goal is to follow, by microarray, the possible alteration of blood cell molecular pathways which may be altered to initiate the process of nervous tissue destruction in the course of T1D. Material and Methods Patients were selected from those attending the diabetic clinic at JUMC Department of Metabolic Disorders. The study group consisted of 60 patients with T1D, confirmed with a positive anti-GAD test result. These patients were treated with a standard therapeutic regimen: multiple daily injections (MDI) or continuous subcutaneous insulin infusions (CSII). The patients were randomized into two subgroups depending on the presence or absence of symptoms of autonomic neuropathy. The control group (n = 20) consisted of healthy non-obese volunteers recruited in accordance to age, gender and body weight. The exclusion criteria for all participants were: age under 20 and above 65 years; metabolic syndrome, cardiovascular diseases, cancer, chronic inflammation; severe liver or kidney failure, iron deficiency anaemia; pregnancy, breast feeding, hormone replacement therapy; anticoagulant treatment; usage of anti-inflammatory drugs and lack of the patient's written consent to participate in the study. The study protocol was approved by the Jagiellonian University Bioethical Committee and was in accordance with the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study. Evaluation of autonomic neuropathy (CAN). The presence of CAN was based on the outcome of the reference method using the ProSciCard apparatus (Ewing test) 13. The severity of the cardiovascular neuropathy in the investigated group was determined by the number of abnormal results (from 3 up to 5) of Ewing test and pathological blood pressure variability [the guidelines for 2018 year of Polish Society of Diabetes] 13. Fasting venous blood was sampled from each participant for further tests. Part of the sample was sent for a routine laboratory diagnostic test, and another part was immediately centrifuged for serum isolation, and then transferred into sterile eppendorfs and stored at −20 °C. Whole blood samples were collected for mRNA isolation using PAXgene Blood RNA Tubes (Becton Dickinson) for material stabilization and transport. Each study participant underwent laboratory tests assessing the level of metabolic control, including: HbA1c level, lipidogram, renal markers, liver function tests and TSH levels. Biochemical tests were performed at the main Laboratory Diagnostics Department in the University Hospital, in accordance with standard procedures. RNA isolation. Purification of total RNA from human whole blood was performed using the PAXgene Blood RNA Kit, following producer protocol. The RNA quality was analysed using the Tapestation 2200 instrument (Agilent, USA) and quantified by spectrophotometry on the NanoDrop

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes

“…A longitudinal study showed that patients with these haplotypes who progressed to clinical diagnosis exhibited differential expression in their plasma of seven other gene products (ADCY9, PTCH1, MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5) that allowed the correct prediction of seroconversion in 85% of the cases [ 26 ]. A recent study in T1D patients also found differential expression of several additional genes involved in inflammation ( IL-1b , IL-1R1 , NFkB1 ), autophagia ( GABARAPL2 , FRAP1 , CTSL , CTSW ), apoptosis ( BCL2L13 ), DNA repair ( APEX1 , ERCC3 , ERCC5 ), and antioxidant activity ( PRDX1 , SOD1 ) [ 27 ]. Another study in peripheral blood mononuclear cells found 450 overexpressed and 245 downregulated genes in T1D patients [ 28 ].…”

Astragaloside IV Ameliorates Inflammatory Damage in Mice with Acute Liver Failure

“…The results also revealed that AS-IV exerted extensive regulatory effects on the expression of autophagy-related genes in liver tissues. A total of 90 genes showed significant changes, including up-regulated genes such as Atg5, Becn1, Atg12, Pten, Htt, indicates reduced tissue inflammation [42], and the decreased expression of Cdkn2a, an aging marker, suggests decreased apoptosis. In conclusion, the mechanism of action of AS-IV in the treatment of acute liver failure involves the regulation of autophagy levels, which may modulate inflammation by enhancing autophagy and inhibiting apoptosis.…”

Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients

“…Oxidative stress can also increase DNA damage, which may activate DNA repair and, depending on the scenario, may also lead to apoptosis [28,29]. Other studies have described upregulation of DNA repair, inflammation, ER-stress response, and apoptosis pathways in T1D patients [30,31]. There is also evidence that oxidative stress and inflammation occur even several months before the onset of T1D in children, favoring the autoimmunity and induced cellular damage in β-cells [32].…”