scholarly journals Systems Approach to Pathogenic Mechanism of Type 2 Diabetes and Drug Discovery Design Based on Deep Learning and Drug Design Specifications

2020 ◽  
Vol 22 (1) ◽  
pp. 166
Author(s):  
Shen Chang ◽  
Jian-You Chen ◽  
Yung-Jen Chuang ◽  
Bor-Sen Chen
Keyword(s):  
Type 2 Diabetes ◽  
Drug Discovery ◽  
Signaling Pathways ◽  
Drug Targets ◽  
Regulatory Networks ◽  
Systems Approach ◽  
Pathogenic Mechanism ◽  
Detection Methods ◽  
Design Specifications

In this study, we proposed a systems biology approach to investigate the pathogenic mechanism for identifying significant biomarkers as drug targets and a systematic drug discovery strategy to design a potential multiple-molecule targeting drug for type 2 diabetes (T2D) treatment. We first integrated databases to construct the genome-wide genetic and epigenetic networks (GWGENs), which consist of protein–protein interaction networks (PPINs) and gene regulatory networks (GRNs) for T2D and non-T2D (health), respectively. Second, the relevant “real GWGENs” are identified by system identification and system order detection methods performed on the T2D and non-T2D RNA-seq data. To simplify network analysis, principal network projection (PNP) was thereby exploited to extract core GWGENs from real GWGENs. Then, with the help of KEGG pathway annotation, core signaling pathways were constructed to identify significant biomarkers. Furthermore, in order to discover potential drugs for the selected pathogenic biomarkers (i.e., drug targets) from the core signaling pathways, not only did we train a deep neural network (DNN)-based drug–target interaction (DTI) model to predict candidate drug’s binding with the identified biomarkers but also considered a set of design specifications, including drug regulation ability, toxicity, sensitivity, and side effects to sieve out promising drugs suitable for T2D.

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 MicroRNAs and Oxidative Stress: An Intriguing Crosstalk to Be Exploited in the Management of Type 2 Diabetes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 802
Author(s):  
Teresa Vezza ◽  
Aranzazu M. de Marañón ◽  
Francisco Canet ◽  
Pedro Díaz-Pozo ◽  
Miguel Marti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Dysfunction ◽  
Non Coding Rnas ◽  
And Oxidative Stress ◽  
Molecular Crosstalk

Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target.

Liver X receptors: new drug targets to treat Type 2 diabetes?

2006 ◽  
Vol 1 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Knut R Steffensen ◽  
Jan-Åke Gustafsson
Keyword(s):  
Type 2 Diabetes ◽  
Drug Targets ◽  
Liver X Receptors ◽  
New Drug ◽  
X Receptors

scholarly journals Type 2 Diabetes Treatment and Drug Development Study

2018 ◽  
Vol 8 (1) ◽  
pp. 22-33 ◽  
Author(s):  
Da-Yong Lu ◽  
Jin-Yu Che ◽  
Nagendra Sastry Yarla ◽  
Hong-Ying Wu ◽  
Ting-Ren Lu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Drug Targets ◽  
Medical Knowledge ◽  
Modern Medicine ◽  
Diabetes Treatment ◽  
Candidate Drug ◽  
The Future ◽  
Type 2 Diabetes Treatment ◽  
And Personalized Medicine

The causality and etio-pathologic risks for patients with Type 2 Diabetes (T2DM) are important areas in modern medicine. Disease complications are largely unpredictable in patients with T2DM. In the future, we welcome therapeutics of both cutting-edge and traditional for anti-diabetic treatments and management with higher efficiency and less cost. Expanding medical knowledge, behavior/life-style notification in healthcare, modern genetic/bioinformatics diagnostic promotion, clinical developments (Traditional Chinese Medicine and personalized medicine) and new drug developments - including candidate drug targets should be implemented in the future. These efforts might be useful avenues for updating anti-diabetic therapeutics globally. This article aims at introducing this information for T2DM treatment boosts.

scholarly journals Genetic effect of Type 2 diabetes to the progression of neurological diseases

2018 ◽  
Author(s):  
Md Habibur Rahman ◽  
Silong Peng ◽  
Chen Chen ◽  
Pietro Lio’ ◽  
Mohammad Ali Moni
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Drug Targets ◽  
Neurological Diseases ◽  
Genetic Effect ◽  
Neurological Dysfunction ◽  
Transcriptional Analysis ◽  
Increased Risk ◽  
Benchmark Datasets

Neurological diseases (NDs) are progressive disorder often advances with age and comorbidities of Type 2 diabetes (T2D). Epidemiological, clinical and neuropathological evidence advocate that patients with T2D are at an increased risk of getting NDs. However, it is very little known how T2D affects the risk and severity of NDs. To tackle these problems, we employed a transcriptional analysis of affected tissues using agnostic approaches to identify overlapping cellular functions. In this study, we examined gene expression microarray human datasets along with control and disease-affected individuals. Differentially expressed genes (DEG) were identified for both T2D and NDs that includes Alzheimer Disease (AD), Parkinson Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Epilepsy Disease (ED), Huntington Disease (HD), Cerebral Palsy (CP) and Multiple Sclerosis Disease (MSD). We have developed genetic association and diseasome network of T2D and NDs based on the neighborhood-based benchmarking and multilayer network topology approaches. Overlapping DEG sets go through protein-protein interaction and gene enrichment using pathway analysis and gene ontology methods, identifying numerous candidate common genes and pathways. Gene expression analysis platforms have been extensively used to investigate altered pathways and to identify potential biomarkers and drug targets. Finally, we validated our identified biomarkers using the gold benchmark datasets which identified corresponding relations of T2D and NDs. Therapeutic targets aimed at attenuating identified altered pathway could ameliorate neurological dysfunction in a T2D patient.

scholarly journals Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes

2019 ◽  
Vol 10 ◽  
Author(s):  
Natalia de M. Lyra e Silva ◽  
Minh P. Lam ◽  
Claudio N. Soares ◽  
Douglas P. Munoz ◽  
Roumen Milev ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Pathogenic Mechanism

scholarly journals Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Rou Shi ◽  
Yingjian Chen ◽  
Yuanjun Liao ◽  
Rang Li ◽  
Chunwen Lin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Noncoding Rnas ◽  
Vascular Complications ◽  
Differentially Expressed ◽  
Circular Rnas

Aims. Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. Methods. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA–miRNA and circRNA–miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE–RAGE signaling pathways of diabetic complications. Results. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE–RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE–RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Conclusion. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.

scholarly journals Correction: A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

2019 ◽  
Vol 10 (9) ◽  
pp. 6203-6203 ◽  
Author(s):  
Sónia Rocha ◽  
Adelaide Sousa ◽  
Daniela Ribeiro ◽  
Catarina M. Correia ◽  
Vera L. M. Silva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Drug Discovery ◽  
Chalcone Derivatives ◽  
Hydrolyzing Enzymes

Correction for ‘A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives’ by Sónia Rocha, et al., Food Funct., 2019, DOI: 10.1039/c9fo01298b.

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