scholarly journals LKB1 Regulates Vascular Macrophage Functions in Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuewen Wang ◽  
Ziwei Liang ◽  
Hong Xiang ◽  
Yanqiu Li ◽  
Shuhua Chen ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Vascular Inflammation ◽  
Foam Cells ◽  
Vital Role ◽  
Potential Mechanism ◽  
Functional Plasticity ◽  
Macrophage Function ◽  
Multiple Processes ◽  
New Ideas ◽  
Liver Kinase B1

Liver kinase B1 (LKB1) is known to shape the regulation of macrophage function by participating in multiple processes including cell metabolism, growth, and polarization. However, whether LKB1 also affects the functional plasticity of macrophages in atherosclerosis has not attracted much attention. Abnormal macrophage function is a pathophysiological hallmark of atherosclerosis, characterized by the formation of foam cells and the maintenance of vascular inflammation. Mounting evidence supports that LKB1 plays a vital role in the regulation of macrophage function in atherosclerosis, including affecting lipid metabolism reprogramming, inflammation, endoplasmic reticulum stress, and autophagy in macrophages. Thus, decreased expression of LKB1 in atherosclerosis aggravates vascular injury by inducing excessive lipid deposition in macrophages and the formation of foam cells. To systematically understand the role and potential mechanism of LKB1 in regulating macrophage functions in atherosclerosis, this review summarizes the relevant data in this regard, hoping to provide new ideas for the prevention and treatment of atherosclerosis.

Recent Development of Small Molecule Glutaminase Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 432-443 ◽  
Author(s):  
Minsoo Song ◽  
Soong-Hyun Kim ◽  
Chun Young Im ◽  
Hee-Jong Hwang
Keyword(s):  
Small Molecule ◽  
Cell Metabolism ◽  
Phase 1 ◽  
Vital Role ◽  
Glutamine Metabolism ◽  
Inhibition Mechanism ◽  
Tumor Cell Growth ◽  
X Ray ◽  
New Class ◽  
Preclinical And Clinical Studies

Glutaminase (GLS), which is responsible for the conversion of glutamine to glutamate, plays a vital role in up-regulating cell metabolism for tumor cell growth and is considered to be a valuable therapeutic target for cancer treatment. Based on this important function of glutaminase in cancer, several GLS inhibitors have been developed in both academia and industry. Most importantly, Calithera Biosciences Inc. is actively developing the glutaminase inhibitor CB-839 for the treatment of various cancers, and it is currently being evaluated in phase 1 and 2 clinical trials. In this review, recent efforts to develop small molecule glutaminase inhibitors that target glutamine metabolism in both preclinical and clinical studies are discussed. In particular, more emphasis is placed on CB-839 because it is the only small molecule GLS inhibitor being studied in a clinical setting. The inhibition mechanism is also discussed based on X-ray structure studies of thiadiazole derivatives present in glutaminase inhibitor BPTES. Finally, recent medicinal chemistry efforts to develop a new class of GLS inhibitors are described in the hopes of providing useful information for the next generation of GLS inhibitors.

scholarly journals The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

2021 ◽  
Vol 22 (15) ◽  
pp. 7931
Author(s):  
Ning Liu ◽  
Shiqiang Sun ◽  
Pengjie Wang ◽  
Yanan Sun ◽  
Qingjuan Hu ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Circulatory System ◽  
Vital Role ◽  
The Body ◽  
Neuroendocrine Cells ◽  
Intestinal Lumen ◽  
Paracrine Signaling ◽  
Inflammatory Conditions ◽  
Epithelial Development ◽  
Ec Cells

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and is reported to modulate the development and neurogenesis of the enteric nervous system, gut motility, secretion, inflammation, sensation, and epithelial development. Approximately 95% of 5-HT in the body is synthesized and secreted by enterochromaffin (EC) cells, the most common type of neuroendocrine cells in the gastrointestinal (GI) tract, through sensing signals from the intestinal lumen and the circulatory system. Gut microbiota, nutrients, and hormones are the main factors that play a vital role in regulating 5-HT secretion by EC cells. Apart from being an important neurotransmitter and a paracrine signaling molecule in the gut, gut-derived 5-HT was also shown to exert other biological functions (in autism and depression) far beyond the gut. Moreover, studies conducted on the regulation of 5-HT in the immune system demonstrated that 5-HT exerts anti-inflammatory and proinflammatory effects on the gut by binding to different receptors under intestinal inflammatory conditions. Understanding the regulatory mechanisms through which 5-HT participates in cell metabolism and physiology can provide potential therapeutic strategies for treating intestinal diseases. Herein, we review recent evidence to recapitulate the mechanisms of synthesis, secretion, regulation, and biofunction of 5-HT to improve the nutrition and health of humans.

scholarly journals Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Metabolism ◽  
Vital Role ◽  
Methionine Metabolism ◽  
Promoter Regions ◽  
Normal Tissues ◽  
Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

scholarly journals The role of exosomal lncRNAs in cancer biology and clinical management

2021 ◽  
Author(s):  
Wuwen Zhang ◽  
Qinshi Wang ◽  
Yi Yang ◽  
Siyuan Zhou ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Clinical Management ◽  
Cancer Biology ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Vital Role ◽  
Cancer Development ◽  
Cancer Cell Proliferation ◽  
Diagnosis And Prognosis ◽  
Multiple Processes

AbstractExosomes play a vital role in cell–cell communication within the cancer microenvironment. Exosomal long noncoding RNAs (lncRNAs) are important regulators in cancer development and are involved in multiple processes, including cancer cell proliferation, angiogenesis, metastasis, drug resistance, and immunomodulation. Changes in the levels of exosomal lncRNAs often appear with the occurrence and development of cancer. Therefore, exosomal lncRNAs can be used as biomarkers for cancer diagnosis and prognosis. Exosomal lncRNAs can also indicate the treatment response of patients receiving chemotherapy. Moreover, exosomal lncRNAs are potential therapeutic targets for cancer treatment. In this review, we summarize the role of exosomal lncRNAs in cancer biology as well as in clinical management. A more comprehensive and in-depth understanding of the role of exosomal lncRNAs in cancer may help us better understand the mechanism of cancer development and clinically manage cancer patients.

Internal Branding as Innovation Tenet

2019 ◽  
pp. 156-182
Author(s):  
Maria Matiatou
Keyword(s):  
Diffusion Of Innovation ◽  
Business Strategy ◽  
New Technology ◽  
Vital Role ◽  
Employee Perceptions ◽  
Internal Branding ◽  
New Ideas ◽  
Communication Practices ◽  
Culture Positive

Innovation as a core value for most organizations is not simply the application of new technology to achieve a business goal: it must be directly expressed through brand experience. Brand driven innovation is human centric. New ideas require a welcoming organizational culture, positive mindsets and internal advocacy to grow. Businesses can really innovate when employees become their brand evangelists. In this chapter, we initially explore internal branding values and tactics. We assess its role as critical bridge over vision, culture and image gaps in case studies to bring awareness on success and risk factors. Employee perceptions of communication practices are captured and matched to aspiration, missions and organizational values. From this premise, we establish internal branding as practice that affects the company's ability to innovate effortlessly and organically. The strong liaison between diffusion of innovation and brand endorsement is confirmed, consolidating the vital role of internal branding in the implementation of an organization's business strategy.

scholarly journals Sirtuins and Autophagy in Age-Associated Neurodegenerative Diseases: Lessons from the C. elegans Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12263
Author(s):  
Anam Naseer ◽  
Snober Shabnam Mir ◽  
Krisztina Takacs-Vellai ◽  
Aamir Nazir
Keyword(s):  
Neurodegenerative Diseases ◽  
Histone Deacetylases ◽  
Vital Role ◽  
Model System ◽  
Dependent Manner ◽  
Class Iii ◽  
C Elegans ◽  
Cell Death Pathways ◽  
Protein Clearance ◽  
Multiple Processes

Age-associated neurodegenerative diseases are known to have “impaired protein clearance” as one of the key features causing their onset and progression. Hence, homeostasis is the key to maintaining balance throughout the cellular system as an organism ages. Any imbalance in the protein clearance machinery is responsible for accumulation of unwanted proteins, leading to pathological consequences—manifesting in neurodegeneration and associated debilitating outcomes. Multiple processes are involved in regulating this phenomenon; however, failure to regulate the autophagic machinery is a critical process that hampers the protein clearing pathway, leading to neurodegeneration. Another important and widely known component that plays a role in modulating neurodegeneration is a class of proteins called sirtuins. These are class III histone deacetylases (HDACs) that are known to regulate various vital processes such as longevity, genomic stability, transcription and DNA repair. These enzymes are also known to modulate neurodegeneration in an autophagy-dependent manner. Considering its genetic relevance and ease of studying disease-related endpoints in neurodegeneration, the model system Caenorhabditis elegans has been successfully employed in deciphering various functional outcomes related to critical protein molecules, cell death pathways and their association with ageing. This review summarizes the vital role of sirtuins and autophagy in ageing and neurodegeneration, in particular highlighting the knowledge obtained using the C. elegans model system.

scholarly journals Inaugural Address

2011 ◽  
Vol 50 (4I) ◽  
pp. 277-278
Author(s):  
Abdul Hafeez Sheikh
Keyword(s):  
Development Economics ◽  
General Meeting ◽  
Vital Role ◽  
Inaugural Address ◽  
Great Pleasure ◽  
Annual General Meeting ◽  
Economic Issues ◽  
Economic Decisions ◽  
Vice Chancellor ◽  
New Ideas

Dr Rashid Amjad, President Pakistan Society of Development Economists and Vice-Chancellor PIDE, distinguished guests, ladies and gentlemen, it gives me great pleasure to address the 27th Annual General Meeting and Conference of the Pakistan Society of Development Economists (PSDE). I am pleased to note that the Society has been instrumental in promoting scholarly research and debate on critical socio-economic issues facing Pakistan, and that the Pakistan Institute of Development Economics (PIDE) has played a vital role in promoting and nurturing the Society since its inception in 1982. The Society has not only upheld and galvanized the profession of development economics in Pakistan but has also helped inspire new ideas for the greater development and prosperity of Pakistan. Ladies and gentlemen, I am happy to see that when I address you today Pakistan's economy is again showing distinct signs of recovery and we hope to achieve a growth rate of 4 to 5 percent this year which should help lift us to a much higher growth trajectory in the future. Despite the heavy headwinds that we have had to face, our government took important fundamental economic decisions of which we can be justly proud.

scholarly journals The antiatherogenic function of kallistatin and its potential mechanism

2020 ◽  
Vol 52 (6) ◽  
pp. 583-589 ◽  
Author(s):  
Gang Wang ◽  
Jin Zou ◽  
Xiaohua Yu ◽  
Shanhui Yin ◽  
Chaoke Tang
Keyword(s):  
Vascular Inflammation ◽  
Serine Proteinase ◽  
Inverse Correlation ◽  
Potential Mechanism ◽  
In Vivo Experiments ◽  
Promising Therapeutic Target ◽  
Artery Disease ◽  
Lipoprotein Receptor Related Protein

Abstract Atherosclerosis is the pathological basis of most cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Kallistatin, originally discovered in human serum, is a tissue-kallikrein-binding protein and a unique serine proteinase inhibitor. Upon binding to its receptor integrin β3, lipoprotein receptor-related protein 6, nucleolin, or Krüppel-like factor 4, kallistatin can modulate various signaling pathways and affect multiple biological processes, including angiogenesis, inflammatory response, oxidative stress, and tumor growth. Circulating kallistatin levels are significantly decreased in patients with coronary artery disease and show an inverse correlation with its severity. Importantly, both in vitro and in vivo experiments have demonstrated that kallistatin reduces atherosclerosis by inhibiting vascular inflammation, antagonizing endothelial dysfunction, and improving lipid metabolism. Thus, kallistatin may be a novel biomarker and a promising therapeutic target for atherosclerosis-related diseases. In this review, we focus on the antiatherogenic function of kallistatin and its potential mechanism.

scholarly journals Association of Serum Chemerin Levels with Coronary Artery Disease: Pathogenesis and Clinical Research

2020 ◽  
Vol 4 (4) ◽  
pp. 251-256
Author(s):  
Lutfu Askin ◽  
Hakan Duman ◽  
Ali Ozyıldız ◽  
Okan Tanriverdi
Keyword(s):  
Cardiovascular Diseases ◽  
Coronary Atherosclerosis ◽  
Essential Role ◽  
Ventricular Dysfunction ◽  
Biological Function ◽  
Vascular Inflammation ◽  
Vital Role ◽  
Left Ventricular ◽  
Peripheral Tissues ◽  
Artery Disease

Recent studies have revealed that chemerin plays an essential role in the development of cardiovascular diseases. Autopsy studies found a strong correlation between the secretion of chemerin in peripheral tissues and aortic and coronary atherosclerosis. Plasma chemerin is a marker of systemic inflammation and is associated with metabolic syndrome. Chemerin plays a vital role in vascular inflammation and atherogenesis. Plasma chemerin levels are increased in patients with dilated cardiomyopathy, and chemerin is associated with left ventricular dysfunction. In this review, we focus on chemerin expression, chemerin processing, its biological function, and its role in the diagnosis of cardiovascular diseases.

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