scholarly journals Environmental Regulation of the Heart: The Role of Non-Coding RNA and Epigenetics in Influencing Mitochondrial and Cellular Health

2019 ◽  
Author(s):  
◽  
Quincy Hathaway ◽  
Keyword(s):  
Regulatory Networks ◽  
Acute Stress ◽  
Inhalation Exposure ◽  
The Body ◽  
Machine Learning Algorithms ◽  
Human Patient ◽  
Non Coding Rna ◽  
Cardiac Mitochondrion ◽  
Predictive Assessments

The mitochondrion, a small but ubiquitously distributed organelle in the cell, continues to be the focus of many disease pathogeneses, tissue and organ dysfunctions, and other morbidities that occur throughout the body. The purpose of this work was to understand how cardiac mitochondrion are altered in disease and pathological states, specifically in their adaptation to environmentally stimulated regulatory networks, such as epigenetic modifications and promotion/inhibition of non-coding RNAs. Acute stress to mitochondrial regulation (inhalation toxicology) as well as chronic (type 2 diabetes mellitus) was examined. Using a FVB transgenic microRNA-378a mouse knockout model, the cardiovascular impact derived from altering the innate microRNA-378a response following acute nano-TiO2 inhalation exposure was evaluated. In atrial tissue from 50 patients (30 non-diabetic and 20 type 2 diabetic) physiological, biochemical, genomic, and epigenomic factors were assessed using machine learning algorithms in an attempt to better predict the pathogenesis of the disease in the heart. Next-generation sequencing was performed on human patient and FVB mouse mitochondrial and cytoplasmic non-coding RNA populations, along with polynucleotide phosphorylase (PNPase) crosslinking immunoprecipitation (CLIP). Ultimately, the work summarized in the preceding experiments highlights how multiple pathological insults, whether chronic or acute, can influence the underlying molecular, regulatory networks in the heart. While overt cardiovascular and mitochondrial dysfunction follow insult, an emphasis on epigenetic control and non-coding RNA regulation may prove to be primary axes for therapeutic intervention. As we continue to pursue more informed and predictive assessments of cardiovascular dysfunction, the mitochondrion remains at the heart of the issue.

scholarly journals Regulatory networks of non-coding RNAs in brown/beige adipogenesis

2015 ◽  
Vol 35 (5) ◽  
Author(s):  
Shaohai Xu ◽  
Peng Chen ◽  
Lei Sun
Keyword(s):  
Regulatory Networks ◽  
The Body ◽  
Bat Activity ◽  
Non Coding Rna ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Beige Fat ◽  
And Function ◽  
Long Non Coding Rna

BAT (brown adipose tissue) is specialized to burn fatty acids for heat generation and energy expenditure to defend against cold and obesity. Accumulating studies have demonstrated that manipulation of BAT activity through various strategies can regulate metabolic homoeostasis and lead to a healthy phenotype. Two classes of ncRNA (non-coding RNA), miRNA and lncRNA (long non-coding RNA), play crucial roles in gene regulation during tissue development and remodelling. In the present review, we summarize recent findings on regulatory role of distinct ncRNAs in brown/beige adipocytes, and discuss how these ncRNA regulatory networks contribute to brown/beige fat development, differentiation and function. We suggest that targeting ncRNAs could be an attractive approach to enhance BAT activity for protecting the body against obesity and its pathological consequences.

Mitochondrial Import of Malat1 Regulates Cardiac Mitochondrial Function in Type 2 Diabetes Mellitus through Interaction with MicroRNA-23b

2020 ◽  
Author(s):  
Quincy A. Hathaway ◽  
Andrew D. Taylor ◽  
Amina Kunovac ◽  
Mark V. Pinti ◽  
Mackenzie S. Newman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Machine Learning ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Function ◽  
Secondary Structures ◽  
Machine Learning Algorithms ◽  
12S Rrna ◽  
Human Patient

Abstract Background: The pathogenesis of type 2 diabetes mellitus is known to alter cardiac mitochondrial bioenergetics, but the role of non-coding RNAs (ncRNAs) in regulating this process remains poorly understood, specifically within the mitochondrion. Here we characterized the mitochondrial localization of nuclear-encoded lncRNAs in the heart in an effort to understand how import of lncRNAs can modify mitochondrial function during diabetes mellitus.Methods: Human patient and FVB/NJ mouse cardiac tissues were collected from type 2 diabetics and non-diabetics. Immunoblotting was used to validate purity of mitochondrial fractionation. NcRNA from subcellular compartments (cytoplasmic and mitochondrial) were sequenced through the Illumina 2500 HiSeq. LncRNA mitochondrial targeting sequences were acquired through crosslinking immunoprecipitation (CLIP) with Polynucleotide Phosphorylase (PNPase) and secondary structures were analyzed using supervised and unsupervised machine learning algorithms. Fluorescence in situ hybridization (FISH) allowed for visualization of Malat1 localization. Mitochondrial function was assessed through oxygen consumption rate.Results: 2448 LncRNAs were discovered in human cardiac mitochondria. Malat1 and microRNA-23b abundance were significantly reduced in human and mouse diabetic mitochondria. Modification of the import protein PNPase in HL-1 cells decreased binding affinity (~80%) of transcript variant 4 of Malat1 (Malat1-204), with machine learning (AUC 0.75) identifying stem-loops as shared secondary structures of lncRNAs bound to PNPase. Knockdown of Malat1-204 and microRNA-23b in mitochondria decreased protein expression of mt-Nd4 (~55%), though showed little/no binding homology to the mt-Nd4 mRNA transcript. Malat1-204 and microRNA-23b were identified bound to mt-Rnr1 rRNA, which could influence translation of mt-Nd4 through the mitochondrial 12S rRNA pathway.Conclusions: Malat1-204 and microRNA-23b, decreased in cardiac diabetic mitochondria, likely stabilize the mitochondrial ribosomal complexes through binding of mt-Rnr1. The significant decrease in total abundance of lncRNAs in diabetic mitochondria could suggest maladaptation for regulating bioenergetics and managing future insults.

Type 2 Machine Learning: An Effective Hybrid Prediction Model for Early Type 2 Diabetes Detection

2020 ◽  
Vol 10 (5) ◽  
pp. 1069-1075
Author(s):  
Saleh Albahli
Keyword(s):  
Machine Learning ◽  
Type 2 Diabetes ◽  
Prediction Model ◽  
Missing Values ◽  
The Body ◽  
Machine Learning Algorithms ◽  
Classification Algorithms ◽  
Hybrid Prediction ◽  
Clustering And Classification

Importance: Diabetes is a chronic disease that can cause long term damage to various parts of the body. To prevent diabetic complications, different attempts integrating machine learning with medicine have been made for building models to predict whether a patient has diabetes or not, but predicting this disease still has room for improvement. Hybrid prediction model presents a novel method and mostly achieve a much better optimal outcome than single classical machine learning algorithms. Objective: To develop a high accuracy model for different onsets of type 2 diabetes prediction. In this way, the integration between clustering and classification techniques can be improved to help detecting diabetes at an earlier stage without deleting observations with missing values and also decrease insignificant features to get the most related features during data collection. Methods: We implement a noise reduction based technique using Kmeans clustering followed by running the Random forest and XGBoost classifiers to extract the unknown hidden features of the dataset and for more accurate results. Results: Prediction accuracy can be observed by benchmarking our model against up-to-date predictive models and common classification algorithms. With an accuracy of 97.53% by 10 fold cross validation, our T2ML model reaches a better accuracy compared with other experiments reported by other researchers in the literature and over various conventional classification algorithms.

Serum Ferritin Status of Patients with Type 2 DM Attending OPD of BIRDEM General Hospital

2020 ◽  
Vol 11 (1) ◽  
pp. 7-10
Author(s):  
Khadiza Begum ◽  
Fahmida Islam ◽  
Farjana Aktar ◽  
Murshida Aziz ◽  
Tohfa E Ayub Tahiya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Serum Ferritin ◽  
Study Groups ◽  
Acute Phase Reactant ◽  
The Body ◽  
Iron Stores ◽  
Normal Healthy Individual ◽  
Diabetes Patients

Background: In recent times much is talked about of serum ferritin, an acute phase reactant a marker of iron stores in the body and its association with diabetes mellitus. Studies implicate that increased body iron stores and subclinical hemochromatosis has been associated with the development of glucose intolerance, type 2 diabetes and its micro as well as macrovascular complications. Material & Methods: This study was carried out to examine and to observe for any relationship between serum ferritin with Type 2 diabetes mellitus. Our study populations were included 163. Among them 81 type 2 diabetes patients as a case (M=49,F=32, mean 44.68 age in years)and 82 normal healthy individual as a control ( M=35, F=47 , mean 34.71 in years). Results: Majority were healthy outpatients who had come for regular checkup and were matched with controls. Serum ferritin and FBS were estimated and other investigations. Results showed that although Serum ferritin was in the normal range value it was increased in type 2 diabetes patients than in controls and was statistically significant, we did get a positive correlation with duration of diabetes. It can be concluded that there were positive associations between serum ferritin and FBG, age, sex among study groups. Conclusion: In conclusion our study shows that there is significant correlation between increased serum ferritin in diabetes compared to individuals with normal blood sugars in this part and hyper ferritinemia may be one of the causes for development of insulin resistance before overt diabetes. Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 7-10

Predicting the citation and impact factor of terms for scientific publications using machine learning algorithms

2020 ◽  
Author(s):  
Aleksey Klokov ◽  
Evgenii Slobodyuk ◽  
Michael Charnine
Keyword(s):  
Machine Learning ◽  
Semantic Processing ◽  
The Body ◽  
Machine Learning Algorithms ◽  
Scientific Publications ◽  
Text Data ◽  
Semantic Relationships ◽  
Subject Areas ◽  
The Subject ◽  
Scientific Environment

The object of the research when writing the work was the body of text data collected together with the scientific advisor and the algorithms for processing the natural language of analysis. The stream of hypotheses has been tested against computer science scientific publications through a series of simulation experiments described in this dissertation. The subject of the research is algorithms and the results of the algorithms, aimed at predicting promising topics and terms that appear in the course of time in the scientific environment. The result of this work is a set of machine learning models, with the help of which experiments were carried out to identify promising terms and semantic relationships in the text corpus. The resulting models can be used for semantic processing and analysis of other subject areas.

FUNCTIONAL STATUS AND ADAPTIVE POTENTIAL IN FOREIGN STUDENTS WITH DIFFERENT TYPES OF VEGETATIVE REGULATION DURING TUITION

2020 ◽  
pp. 118-126
Author(s):  
A.M. Satarkulova
Keyword(s):  
Heart Rate ◽  
Foreign Students ◽  
Autonomic Regulation ◽  
The Body ◽  
Functional Changes ◽  
Different Types ◽  
Type 3 ◽  
Adaptive Abilities

The assessment and dynamic control over students’ status is a very important task. It allows timely detection of prenosological status prior to pathology and health maintenance in students. The objective of the paper is to assess the adaptive abilities of the body, to analyze changes in heart rate variability indicators in students with various types of autonomic regulation, to identify prenosological status and precursory pathological symptoms. Materials and Methods. The study enrolled 302 students from India, aged 21.54±1.43. Programming complex «Psychophysiologist» was used to register the main HRV parameters within 5 minutes. Health status was evaluated according to the index of functional changes and the scale of functional states. Results. N.I. Shlyk (2009) distinguished two groups of students with different types of autonomic regulation: type 1 (53 %) with moderate and type 2 (5 %) with marked characteristics of central regulation profile, type 3 (35 %) with moderate and type 4 (7 %) with marked characteristics of autonomous regulation profile. Main parameters of HRV and adaptation potential were defined for each student.All the parameters characterized functional and health status. Conclusions. It was shown that 82 % of trial subjects (type 1), 53 % (type 2), 94 % (type 3) and 95 % (type 4) demonstrated satisfactory adaptation and their physiological processes were at an optimal level. 18 % of students (type 1) demonstrated reduced adaptive abilities of the body. Moreover, they were under moderate stress. 47 % of subjects (type 2) were also under a significant stress, which was proven by excessively high SI, low SDNN and TP, and an increased index of functional changes. 5 % of students (type 4) revealed dysfunctional characteristics in the heart rhythm, peculiar to pathology. Keywords: foreign students, heart rate variability, types of autonomic regulation, adaptation potential, functional status. Оценка состояния студентов и динамический контроль за ним является важной задачей, поскольку позволяет своевременно выявлять у студентов донозологические состояния, предшествующие патологии, и способствовать сохранению здоровья. Цель. Оценка адаптивных возможностей организма, анализ изменений показателей вариабельности сердечного ритма у студентов с различными типами вегетативной регуляции, выявление донозологических состояний и ранних признаков патологии. Материалы и методы. В исследовании участвовало 302 студента в возрасте 21,54+1,43 года из Индии. Регистрировались основные параметры ВСР в течение 5 мин с использованием программно-аппаратного комплекса «Психофизиолог». Состояние и уровень здоровья оценивались по индексу функциональных изменений и шкале функциональных состояний. Результаты. По способу, предложенному Н.И. Шлык, выделены группы студентов с различными типами вегетативной регуляции: I (53 %) и II типы (5 %) – с умеренным и выраженным преобладанием центрального контура регуляции соответственно, III (35 %) и IV типы (7 %) – с умеренным и выраженным преобладанием автономного контура регуляции соответственно. У каждого из студентов определены основные параметры ВСР и адаптационного потенциала, характеризующие функциональное состояние и уровень здоровья. Выводы. Показано, что для 82 % обследуемых с I типом, 53 % со II типом, 94 % c III типом и 95 % с IV типом регуляции характерно состояние удовлетворительной адаптации, физиологические процессы сохраняются на оптимальном уровне. В группе студентов I типа у 18 % студентов адаптивные возможности организма снижены, выявлено состояние умеренного напряжения. У 47 % обследуемых II типа также зафиксировано состояние резко выраженного напряжения, индикатором которого является чрезмерно высокое значение SI, низкие величины SDNN и ТP, повышенное значение индекса функциональных изменений. В группе студентов с IV типом у 5 % учащихсяв регуляции ритма сердца выявлены дисфункциональные признаки, характерные для патологии. Ключевые слова: иностранные студенты, вариабельность сердечного ритма, типы вегетативной регуляции, адаптационный потенциал, функциональное состояние.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

scholarly journals Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Repeated Measures ◽  
Medical Information ◽  
Controlled Trial ◽  
Extracellular Volume ◽  
Cardiovascular Outcomes ◽  
Fluid Volume ◽  
The Body

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

scholarly journals Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Saara Marttila ◽  
Leena E. Viiri ◽  
Pashupati P. Mishra ◽  
Brigitte Kühnel ◽  
Pamela R. Matias-Garcia ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Methylation Status ◽  
Induced Pluripotent Stem Cell ◽  
Methylation Pattern ◽  
Rna Expression ◽  
Non Coding Rna ◽  
Mother’S Age ◽  
Induced Pluripotent ◽  
Metastable Epiallele

Abstract Background Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. Results We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. Conclusions These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.

scholarly journals Rap1a Overlaps the AGE/RAGE Signaling Cascade to Alter Expression of α-SMA, p-NF-κB, and p-PKC-ζ in Cardiac Fibroblasts Isolated from Type 2 Diabetic Mice

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 557
Author(s):  
Stephanie D. Burr ◽  
James A. Stewart
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Hydrogen Peroxide ◽  
Cardiac Fibroblasts ◽  
The Body ◽  
Signaling Cascade ◽  
Diabetic Mice ◽  
Pkc Ζ ◽  
Type 2 Diabetic

Cardiovascular disease, specifically heart failure, is a common complication for individuals with type 2 diabetes mellitus. Heart failure can arise with stiffening of the left ventricle, which can be caused by “active” cardiac fibroblasts (i.e., myofibroblasts) remodeling the extracellular matrix (ECM). Differentiation of fibroblasts to myofibroblasts has been demonstrated to be an outcome of AGE/RAGE signaling. Hyperglycemia causes advanced glycated end products (AGEs) to accumulate within the body, and this process is greatly accelerated under chronic diabetic conditions. AGEs can bind and activate their receptor (RAGE) to trigger multiple downstream outcomes, such as altering ECM remodeling, inflammation, and oxidative stress. Previously, our lab has identified a small GTPase, Rap1a, that possibly overlaps the AGE/RAGE signaling cascade to affect the downstream outcomes. Rap1a acts as a molecular switch connecting extracellular signals to intracellular responses. Therefore, we hypothesized that Rap1a crosses the AGE/RAGE cascade to alter the expression of AGE/RAGE associated signaling proteins in cardiac fibroblasts in type 2 diabetic mice. To delineate this cascade, we used genetically different cardiac fibroblasts from non-diabetic, diabetic, non-diabetic RAGE knockout, diabetic RAGE knockout, and Rap1a knockout mice and treated them with pharmacological modifiers (exogenous AGEs, EPAC, Rap1a siRNA, and pseudosubstrate PKC-ζ). We examined changes in expression of proteins implicated as markers for myofibroblasts (α-SMA) and inflammation/oxidative stress (NF-κB and SOD-1). In addition, oxidative stress was also assessed by measuring hydrogen peroxide concentration. Our results indicated that Rap1a connects to the AGE/RAGE cascade to promote and maintain α-SMA expression in cardiac fibroblasts. Moreover, Rap1a, in conjunction with activation of the AGE/RAGE cascade, increased NF-κB expression as well as hydrogen peroxide concentration, indicating a possible oxidative stress response. Additionally, knocking down Rap1a expression resulted in an increase in SOD-1 expression suggesting that Rap1a can affect oxidative stress markers independently of the AGE/RAGE signaling cascade. These results demonstrated that Rap1a contributes to the myofibroblast population within the heart via AGE/RAGE signaling as well as promotes possible oxidative stress. This study offers a new potential therapeutic target that could possibly reduce the risk for developing diabetic cardiovascular complications attributed to AGE/RAGE signaling.

Sign in / Sign up

Export Citation Format

Share Document