In-Silico Study of Immune System Associated Genes in Case of Type-2 Diabetes With Insulin Action and Resistance, and/or Obesity

Type-2 diabetes and obesity are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex and heterogeneous in nature. Based on epidemiological evidence, it is known that the patients suffering from obesity are considered to be at a significantly higher risk of type-2 diabetes. There are several pieces of evidence that support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of type-2 diabetes. Multi-level unwanted alterations such as (epi-) genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources that promote several complex diseases, and such a heterogeneous level of complexity is considered as a major barrier in the development of therapeutics. With so many known challenges, it is critical to understand the relationships and the shared causes between type-2 diabetes and obesity, and these are difficult to unravel and understand. For this purpose, we have selected publicly available datasets of gene expression for obesity and type-2 diabetes, have unraveled the genes and the pathways associated with the immune system, and have also focused on the T-cell signaling pathway and its components. We have applied a simplified computational approach to understanding differential gene expression and patterns and the enriched pathways for obesity and type-2 diabetes. Furthermore, we have also analyzed genes by using network-level understanding. In the analysis, we observe that there are fewer genes that are commonly differentially expressed while a comparatively higher number of pathways are shared between them. There are only 4 pathways that are associated with the immune system in case of obesity and 10 immune-associated pathways in case of type-2 diabetes, and, among them, only 2 pathways are commonly altered. Furthermore, we have presented SPNS1, PTPN6, CD247, FOS, and PIK3R5 as the overexpressed genes, which are the direct components of TCR signaling.

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Type 2 Diabetes, Obesity, and Cancer Share Some Common and Critical Pathways

Frontiers in Oncology ◽

10.3389/fonc.2020.600824 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ishrat Rahman ◽

Md Tanwir Athar ◽

Mozaffarul Islam

Keyword(s):

Type 2 Diabetes ◽

Complex Diseases ◽

Genetic Alterations ◽

Cancer Prognosis ◽

Transcriptional Level ◽

Major Barrier ◽

Critical Pathways ◽

Cancer Types ◽

Obesity And Cancer

Diabetes and cancer are among the most frequent and complex diseases. Epidemiological evidence showed that the patients suffering from diabetes are significantly at higher risk for a number of cancer types. There are a number of evidence that support the hypothesis that these diseases are interlinked, and obesity may aggravate the risk(s) of type 2 diabetes and cancer. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic agents. With so many known challenges, it is critical to understand the relationships and the commonly shared causes between type 2 diabetes and cancer, which is difficult to unravel and understand. Furthermore, the real complexity arises from contended corroborations that specific drug(s) (individually or in combination) during the treatment of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidence from the studies where the origin, biological background, the correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. We have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases, diabetes and cancer.

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In-Silico Study of the Immune Systems Associated Genes in Case of Type-2 Diabetes with Insulin Action and Resistance and in Obesity

10.20944/preprints202010.0316.v1 ◽

2020 ◽

Author(s):

Basmah Medhat Eldakhakhny ◽

Hadeel Al Sadoun ◽

Hani Choudhry ◽

Mohammad Mobashir

Keyword(s):

Type 2 Diabetes ◽

Complex Diseases ◽

Genetic Alterations ◽

Cancer Prognosis ◽

Transcriptional Level ◽

Therapeutic Approaches ◽

Major Barrier ◽

In Silico Study ◽

Cancer Types

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

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COVID-19 candidate genes and pathways potentially share the association with lung cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210712092649 ◽

2021 ◽

Vol 24 ◽

Author(s):

Afnan M. Alnajeebi ◽

Hend F.H. Alharbi ◽

Walla Alelwani ◽

Nouf A. Babteen ◽

Wafa Alansari ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Research Work ◽

Genetic Alterations ◽

Transcriptional Level ◽

Major Barrier ◽

Growth Inhibitory ◽

New Finding ◽

Apoptotic Pathways ◽

Functional Components

: COVID-19 is considered the most challenging in the current situation. At the same time, lung cancer is also the leading cause of death in the global population and is among the top human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex, and heterogeneous. Based on the latest update, it is known that the patients who have lung cancer are considered to be significantly at higher risk after COVID-19 infection in terms of survival, and there are a number of pieces of evidence that support the hypothesis that these diseases may share the functions and the functional components. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases, and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the commonly shared aberrations between them, which is difficult to unravel and understand. A simple approach has been applied for this study where differential gene expression analysis, pathway enrichment, and network-level understanding. Since gene expression changes and genomic alterations are related to COVID-19 and lung cancer, their pattern varies significantly. Based on the recent studies, the patients who have lung cancer and if it gets infected with COVID-19, there is less survival chance. So, we have designed our goal to understand the genes commonly overexpressed and the commonly enriched pathways in the case of COVID-19 and lung cancer, for which we have presented the summarized review of the previous work where the pathogenesis of lung cancer and COVID-19 infection have been focused and further we have also presented the new finding of our analysis. So, this work shows not only the review work but also the research work. This review and research study leads to the conclusion that growth-promoting pathways (EGFR, Ras, and PI3K), growth inhibitory pathways (p53 and STK11), apoptotic pathways (Bcl-2/Bax/Fas), and DDR pathways and genes are commonly and dominantly altered in both the cases COVID-19 and lung cancer.

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Role of potential COVID-19 immune system associated genes and the potential pathways linkage with type-2 diabetes

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210804124416 ◽

2021 ◽

Vol 24 ◽

Author(s):

Nawal Helmi ◽

Dalia Alammari ◽

Mohammad Mobashir

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Immune System ◽

Expression Patterns ◽

Osteoclast Differentiation ◽

Gene Expression Pattern ◽

Common Source ◽

Altered Gene Expression ◽

Altered Gene

Background: Coronavirus is an enveloped positive-sense RNA virus and is characterized by club-like spikes projecting from its surface which is commonly associated with acute respiratory infections in humans but its ability to infect multiple host species and multiple diseases brings it to a complex pathogen group. The frequent interactions of wild animals with humans it is more prevalent a common source of such infections and SARS—CoV and MERS—CoV are the zoonotic pathogens among the leading cause of severe respiratory diseases in humans. Aim: The major purpose of this study was to study the gene expression profiling for those human samples which are infected with coronavirus or uninfected and compare the differential expression patterns and its functional impact. Methods: For this purpose, the previously studied samples have been collected from public database and the study had been performed and it includes gene expression analysis, pathway analysis, and the network-level understanding. The analysis presents the data for the differentially expressed genes, enriched pathways and the networks for the potential genes and gene sets. In terms of gene expression and the linkage of COVID-19 with type-2 diabetes. Results: We observe that there are a large number of genes which show altered gene expression pattern than the normal for coronavirus infection while in terms of pathways it appears that there are few sets of functions which are affected due to altered gene expression and they infer to infection, inflammation, and the immune system. Conclusions: Based on our study, we conclude that the potential genes which are affected due to infection are NFKBIA, MYC, FOXO3, BIRC3, ICAM1, IL8, CXCL1/2/5, GADD45A, RELB, SGK1, AREG, BBC3, DDIT3/4, EGR1, MTHFD2, and SESN2 and the functional changes are mainly associated with these pathways TNF, cytokine, NF—kB, TLR, TCR, BCR, Foxo, and TGF signaling pathways are among them and there are additional pathways such as hippo signaling, apoptosis, estrogen signaling, regulating pluropotency of stem cells, ErbB, Wnt, p53, cAMP, MAPK, PI3K—AKT, oxidative phosphorylation, protein processing in endoplasmic reticulum, prolactin signaling, adipocytokine, neurotrophine signaling, and longevity regulating pathways. SMARCD3, PARL, GLIPR1, STAT2, PMAIP1, GP1BA, and TOX genes and PI3K-Akt, focal adhesion, Foxo, phagosome, adrenergic, osteoclast differentiation, platelet activation, insulin, cytokine-cytokine interaction, apoptosis, ECM, JAK-STAT, and oxytocine signaling appear as the linkage between COVID-19 and Type-2 diabetes.

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Alterations of Gut Microbiota by Overnutrition Impact Gluconeogenic Gene Expression and Insulin Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms22042121 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2121 ◽

Cited By ~ 1

Author(s):

Ling He

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Insulin Signaling ◽

Intestinal Barrier ◽

Glucose Production ◽

Predisposing Factor ◽

Acetyltransferase Activity ◽

Microbial Profile ◽

Diabetes And Obesity

A high-fat, Western-style diet is an important predisposing factor for the onset of type 2 diabetes and obesity. It causes changes in gut microbial profile, reduction of microbial diversity, and the impairment of the intestinal barrier, leading to increased serum lipopolysaccharide (endotoxin) levels. Elevated lipopolysaccharide (LPS) induces acetyltransferase P300 both in the nucleus and cytoplasm of liver hepatocytes through the activation of the IRE1-XBP1 pathway in the endoplasmic reticulum stress. In the nucleus, induced P300 acetylates CRTC2 to increase CRTC2 abundance and drives Foxo1 gene expression, resulting in increased expression of the rate-limiting gluconeogenic gene G6pc and Pck1 and abnormal liver glucose production. Furthermore, abnormal cytoplasm-appearing P300 acetylates IRS1 and IRS2 to disrupt insulin signaling, leading to the prevention of nuclear exclusion and degradation of FOXO1 proteins to further exacerbate the expression of G6pc and Pck1 genes and liver glucose production. Inhibition of P300 acetyltransferase activity by chemical inhibitors improved insulin signaling and alleviated hyperglycemia in obese mice. Thus, P300 acetyltransferase activity appears to be a therapeutic target for the treatment of type 2 diabetes and obesity.

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