scholarly journals Different obesity phenotypes correlated with the PI3K-AKT signaling pathway in tree shrews

2018 ◽  
Author(s):  
Yuanyuan Han ◽  
Huatang Zhang ◽  
Jiejie Dai ◽  
Yang Chen
Keyword(s):  
Tree Shrew ◽  
Treatment Strategies ◽  
Vital Role ◽  
Strongly Correlated ◽  
Hub Genes ◽  
Tree Shrews ◽  
Obesity Phenotype ◽  
Highly Correlated ◽  
First Time

AbstractObjectiveTo identify the meaningful co-expressed gene network in mRNA extracted from adipose tissue representing different obesity phenotypes in a new tree shrew model. Furthermore, to locate the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity.MethodsTen tree shrews were selected from F1 populations and divided into 3 groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) by weighted gene co-expression network analysis (WGCNA).ResultsThree modules were strongly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P < 0.01). The ribosome, lysosome and ubiquitin-mediated proteolysis pathways were the most enriched pathways of the blue (including 481 genes), brown (389 genes) and turquoise (1781 genes) modules, respectively. The hub genes were determined, including UBA52 in the blue module, AKT1 in the brown module and LRRK2 in the turquoise module.ConclusionsWe characterized different obesity phenotypes in tree shrews for the first time. The most represented gene AKT1 indicated the vital role of the PI3K-AKT pathway through interactions with downstream pathways and differentially expressed genes (DEGs). The work will help provide new insight into the prevention and treatment strategies of obesity.

scholarly journals PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Dawei Chen ◽  
Zhenguo Zhao ◽  
Lu Chen ◽  
Qinghua Li ◽  
Jixue Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Alternative Splicing ◽  
Protein Function ◽  
Vital Role ◽  
Normal Tissues ◽  
Mechanistic Analysis ◽  
Highly Correlated ◽  
Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

Identification of critical genes and pathways involved in intervertebral disc degeneration (IDD) An integrated bioinformatics analysis

2020 ◽  
Author(s):  
Jingyang Zhou ◽  
Feng Xin ◽  
Chuyu Xiao ◽  
Wuyuan Zhou
Keyword(s):  
Daily Life ◽  
Vital Role ◽  
Ppi Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Diagnosis And Prognosis ◽  
Study Results ◽  
Validation Experiment ◽  
The One

Abstract Background: In western countries and China, back and neck pain has become a common problem that bothers daily life and severely influences the quality of our daily life. Among all factors that lead to chronic neck and back pain, IDD is the one that couldn’t be easily neglected. Methods: This study aims to figure out the critical genes and pathways involved in the development of IDD and provide a new aspect of following investigations on the etiology of IDD. We firstly systemically searched the GEO database and identified the differentially expressed genes (DEGs) from the expression profile dataset we selected. We secondly constructed the protein-protein interaction (PPI) network for DEGs, identified the top ten hub genes from the whole PPI network and found two statically and medically significant modules from the network, we then performed the GO and KEGG analysis on the DEGs, top ten hub genes, the PPI network and the two statically and medically modules. In the end, we provided the primers of the mRNAs of all DEGs, which will be useful for the validation experiment of this study. Results: FN1, MMP2, POSTN, COL3A1, TIMP3, FBN1, GJA1, TGFBI, EFEMP1 and ID1 were top ten hub genes identified from this study, and they may play a vital role in the development of IDD. Angiogenesis and integrin binging are crucial biological process and molecular function defined in this study, which are worthy of being intensely investigated.Conclusion: More studies on the top ten hub genes, the role of angiogenesis and integrin binding in IDD are urgently needed, which will benefit the prevention, screening, diagnosis and prognosis of IDD.

scholarly journals Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice

2021 ◽  
Vol 22 (2) ◽  
pp. 524
Author(s):  
Laurent Suissa ◽  
Pavel Kotchetkov ◽  
Jean-Marie Guigonis ◽  
Emilie Doche ◽  
Ophélie Osman ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Neurological Diseases ◽  
Feedback Mechanism ◽  
Strongly Correlated ◽  
Acetyl Coa ◽  
First Time ◽  
The Brain ◽  
Ketone Ester

The role of ketone bodies in the cerebral energy homeostasis of neurological diseases has begun to attract recent attention particularly in acute neurological diseases. In ketogenic therapies, ketosis is achieved by either a ketogenic diet or by the administration of exogenous ketone bodies. The oral ingestion of the ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is a new method to generate rapid and significant ketosis (i.e., above 6 mmol/L) in humans. KE is hydrolyzed into β-hydroxybutyrate (βHB) and its precursor 1,3-butanediol. Here, we investigate the effect of oral KE administration (3 mg KE/g of body weight) on brain metabolism of non-fasted mice using liquid chromatography in tandem with mass spectrometry. Ketosis (Cmax = 6.83 ± 0.19 mmol/L) was obtained at Tmax = 30 min after oral KE-gavage. We found that βHB uptake into the brain strongly correlated with the plasma βHB concentration and was preferentially distributed in the neocortex. We showed for the first time that oral KE led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice. Furthermore, we found that the increased level of acetyl-CoA inhibited glycolysis by a feedback mechanism and thus competed with glucose under physiological conditions. The brain pharmacodynamics of this oral KE strongly suggest that this agent should be considered for acute neurological diseases.

scholarly journals The Next Step is Digital Leadership

2021 ◽  
Vol 1 (2) ◽  
pp. 59-63
Author(s):  
Rana Jisr
Keyword(s):  
Communication Skills ◽  
Online Communication ◽  
Vital Role ◽  
Digital Transformation ◽  
Working Environment ◽  
Digital World ◽  
New Challenges ◽  
First Time ◽  
Shed Light

The aim of this article is to shed light on the vital role of digital leaders in today’s businesses. Many firms have already grounded their partnership with digital transformation before the pandemic. Others sped up all efforts to implement digital capabilities due to COVID-19 for the first time for survival. So, we tried to show that a digital leader needs additional requirements to face the new challenges of working remotely. Furthermore, we think that good online communication skills with digital leaders draw a compelling composite picture of an effective working environment in a digital world.

scholarly journals Identification of Differentially Expressed Genes Reveals BGN Predicting Overall Survival and Tumor Immune Infiltration of Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Weizhi Chen ◽  
Zhongheng Yang
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Differentially Expressed Genes ◽  
Treatment Strategies ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Positive Correlations ◽  
First Time

Gastric cancer (GC) is one of the most widely occurring malignancies worldwide. Although the diagnosis and treatment strategies of GC have been greatly improved in the past few decades, the morbidity and lethality rates of GC are still rising due to lacking early diagnosis strategies and powerful treatments. In this study, a total of 37 differentially expressed genes were identified in GC by analyzing TCGA, GSE118897, GSE19826, and GSE54129. Using the PPI database, we identified 17 hub genes in GC. By analyzing the expression of hub genes and OS, MFAP2, BGN, and TREM1 were related to the prognosis of GC. In addition, our results showed that higher levels of BGN exhibited a significant correlation with shorter OS time in GC. Nomogram analysis showed that the dysregulation of BGN could predict the prognosis of GC. Moreover, we revealed that BGN had a markedly negative correlation with B cells but had positive correlations with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC samples. The pan-cancer analysis demonstrated that BGN was differentially expressed and related to tumor-infiltrating immune cells across human cancers. This study for the first time comprehensively revealed that BGN was a potential biomarker for the prediction of GC prognosis and tumor immune infiltration.

scholarly journals Elevated IL-6R on CD4+ T cells promotes IL-6 driven Th17 cell responses in patients with T1R leprosy reactions

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chaman Saini ◽  
Rupesh K. Srivastava ◽  
Mohd. Tarique ◽  
Santosh Kurra ◽  
Neena Khanna ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treatment Strategies ◽  
Vital Role ◽  
Dependent Manner ◽  
Leprosy Reactions ◽  
Th17 Cell Differentiation ◽  
Leprosy Patients ◽  
First Time

Abstract Th17 cells play vital role during pathogenesis of leprosy reactions. Previously, we have reported that IL-23 is involved in Th17 cells differentiation. Subsequently, our group also showed that IL-6 induces Th17 cell differentiation along with TGF-β in leprosy reactions. Here, we next asked the question that whether IL-6 or IL-23 induced Th17 cells are different in nature? In this study, Type 1 Reactions (T1R) showed significantly (p < 0.001) higher percentage of IL-17A producing CD4+IL6R+ T cells as compared to non-reaction (NR) patients. Furthermore, recombinant IL-6, IL-23 and TGF-β promoted IL-17A secretion by CD4+IL6R+ T cells. Subsequently, IL-6R and IL-23R blocking experiments showed significantly (p < 0.002) down regulated IL-17A in T1R reaction as compared to NR leprosy patients. The present study for the first time establishes that pathogenic Th17 cells produce IL-17 in an IL-6 dependent manner in leprosy T1R reactions. Thus, present approaches that specifically target Th17 cells and/or the cytokines that promote their development, such as IL-6, TGF-β and IL-23A may provide more focused treatment strategies for the management of Mycobacterium leprae and its reactions.

scholarly journals A Study on the Impact of COVID-19 on the Consumer Buying Behavior in E-Commerce in India

2021 ◽  
pp. 67-78
Author(s):  
Beena Thomas
Keyword(s):  
Online Shopping ◽  
Vital Role ◽  
Buying Behavior ◽  
The World ◽  
Brick And Mortar ◽  
Physical Interactions ◽  
Retail Shopping ◽  
The Impact ◽  
First Time

People all over the world have limited their physical interactions as a result of the COVID-19 pandemic. Self-imposed social distance to prevent contagion, combined with strict confinement policies introduced in many nations, has effectively placed a significant portion of conventional brick-and-mortar retail on hold, at least for the time being. This study investigates the impact of covid-19 on consumers buying behavior and pattern in the e-commerce industry which determines the vital role of e-commerce during this pandemic. This study also focuses on consumers’ satisfaction towards online shopping and e-commerce. The result indicated that many of the respondents tried online shopping for the first time due to the COVID pandemic. The majority of the respondents increased their frequency of shopping through e-commerce companies since the outbreak and the major factor in the increase was convenience and offers and discounts available. The majority of respondents agree that e-commerce is important during the pandemic and prefer online shopping to brick-and-mortar retail shopping. They also indicated that that they will continue to shop online even after the pandemic is over.

Identification of Potential Immune-related Biomarkers in Gastrointestinal Cancers

2021 ◽  
Vol 15 ◽  
Author(s):  
Tianyu Zhu ◽  
Qi Dai ◽  
Ping-an He
Keyword(s):  
Immune System ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Immune Genes ◽  
Diagnosis And Prognosis ◽  
Gi Cancers ◽  
Highly Correlated ◽  
Underlying Mechanisms ◽  
Potential Biomarkers

Objectives: Gastrointestinal (GI) cancers, which is the most common and lethal malignant tumor, while limited research and biomarkers are available to stratify patients who are likely to benefit from immunotherapy in GI cancers. During early diagnosis and prognosis of GI cancers, searching for shared potential biomarkers and differences among stages is an urgent and challenging task. The staging RNA expression data corresponding to immune genes were analyzed to infer of the immune system in each stage of GI cancers. Methods: The differential expression gene analysis was performed to analyze the expression of 758 immune genes between normal and each stage samples of GI cancers. Enrichment analysis including GO and KEGG pathway analysis were carried out to investigate the role of these differential genes and underlying mechanisms in GI cancers. Furthermore, PPI network analysis recognized the hub genes among these DEGs. Overall survival analysis was processed to clarify the diagnostic and prognostic role of these potential biomarkers in early and advanced stage. Results: Our present work revealed the immunological commonness and differences across stages of GI cancers, and disclosed several potential immune-related biomarkers, including CCL20, C7, CD36, CXCL11, and CLEC5A. The potential biological function which immune system participates across the GI cancers was highly correlated with virus and membrane. Conclusions: Our result facilitates to understand the involvement of immune system in GI cancers and better design treatment strategies based on current cancer immunotherapy.

Role of the lactate transporter (MCT1) in skeletal muscles

1996 ◽  
Vol 271 (1) ◽  
pp. E143-E150 ◽  
Author(s):  
K. J. McCullagh ◽  
R. C. Poole ◽  
A. P. Halestrap ◽  
M. O'Brien ◽  
A. Bonen
Keyword(s):  
Oxidative Metabolism ◽  
Skeletal Muscles ◽  
Citrate Synthase ◽  
Oxidative Capacity ◽  
Monocarboxylate Transporter ◽  
Strongly Correlated ◽  
Monocarboxylate Transporter 1 ◽  
Highly Correlated ◽  
Fast Twitch

We used an antibody, constructed against the monocarboxylate transporter 1 (MCT1) protein (L. Carpenter, R. C. Poole, and A. P. Halestrap. Biochim. Biophys. Acta 1279: 157-165, 1996), to study the expression and role of MCT1 in rat skeletal muscles. MCT1 was higher in red than in white muscles (P < 0.05) and was highly correlated with the oxidative fiber content (%slow-twitch oxidative + %fast-twitch oxidative glycolytic) of skeletal muscles (r = 0.91). MCT1 was highly related to lactate uptake in skeletal muscles (r = 0.90). Total lactate dehydrogenase (LDH) activity, an index of glycolysis, was negatively correlated with MCT1 in rat muscles (r = -0.80). MCT1 was also strongly correlated with the heart-type forms of LDH (LDH-1 vs. MCT1, r = 0.83; LDH-2 vs. MCT1, r = 0.89). There was no relationship between MCT1 and the muscle form of LDH (LDH-5; P > 0.05). MCT1 was highly correlated with citrate synthase activity, a marker of the oxidative capacity of muscle (r = 0.82). Therefore, MCT1 may have kinetics that favor the uptake of L-lactate into the muscle cell for oxidative metabolism, and MCT1 may be coordinately expressed with the heart forms of LDH and enzymes of oxidative metabolism.

scholarly journals Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 565 ◽  
Author(s):  
Katherine M. Audsley ◽  
Alison M. McDonnell ◽  
Jason Waithman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Vital Role ◽  
Cell Responses ◽  
Cell Immunity ◽  
Patient Responses

The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses.

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