scholarly journals YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Wang ◽  
Yening Zhang ◽  
Xueming Xu ◽  
Jianfeng Wu ◽  
Yue Peng ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Hippo Pathway ◽  
Size Control ◽  
Vital Role ◽  
Potential Therapeutic Target ◽  
Host Immune Responses ◽  
Underlying Mechanisms ◽  
The Stability

AbstractThe transcription coactivator YAP plays a vital role in Hippo pathway for organ-size control and tissue homeostasis. Recent studies have demonstrated YAP is closely related to immune disorders and inflammatory diseases, but the underlying mechanisms remain less defined. Here, we find that YAP promotes the activation of NLRP3 inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile injuries. YAP deficiency in myeloid cells significantly attenuates LPS-induced systemic inflammation and monosodium urate (MSU) crystals-induced peritonitis. Mechanistically, YAP physically interacts with NLRP3 and maintains the stability of NLRP3 through blocking the association between NLRP3 and the E3 ligase β-TrCP1, the latter increases the proteasomal degradation of NLRP3 via K27-linked ubiquitination at lys380. Together, these findings establish a role of YAP in the activation of NLRP3 inflammasome, and provide potential therapeutic target to treat the NLRP3 inflammasome-related diseases.

scholarly journals The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chang ◽  
Hao Li ◽  
Hui Hu ◽  
Yongqing Li ◽  
Tianbing Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Histone Deacetylase 6 ◽  
Physiological Processes ◽  
Class Iib ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Insight Into

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

Chemokines: A Potential Therapeutic Target to Suppress Autoimmune Arthritis

2019 ◽  
Vol 25 (27) ◽  
pp. 2937-2946 ◽  
Author(s):  
Mahmood A. Khan ◽  
Nikhil Khurana ◽  
Rafat S. Ahmed ◽  
Sadiq Umar ◽  
Abu H. Md. G. Sarwar ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Cartilage Destruction ◽  
Vital Role ◽  
Future Perspective ◽  
Potential Therapeutic Target ◽  
Mortality And Morbidity ◽  
The Future

Background:: Chemokines are a family of low molecular weight proteins that induce chemotaxis of inflammatory cells, which mainly depends on the recognition of a chemo-attractant gradient and interaction with the substratum. In Rheumatoid Arthritis (RA), abundant chemokines are expressed in synovial tissue, cause inflammatory cells migration into the inflamed joint that necessitates the formation of new blood vessels i.e. angiogenesis. Over the decades, studies showed that continuous inflammation may lead to the loss of tissue architecture and function, causing severe disability and cartilage destruction. In spite of the advancement of modern drug therapy, thousands of arthritic patients suffer mortality and morbidity globally. Thus, there is an urgent need for the development of novel therapeutic agents for the treatment of RA. Methods:: This review is carried out throughout a non-systematic search of the accessible literature, will provide an overview of the current information of chemokine in RA and also exploring the future perspective of the vital role of targeting chemokine in RA treatment. Results:: Since, chemokines are associated with inflammatory cells/leucocyte migration at the site of inflammation in chronic inflammatory diseases and hence, blockade or interference with chemokines activity showing a potential approach for the development of new anti-inflammatory agents. Currently, results obtained from both preclinical and clinical studies showed significant improvement in arthritis. Conclusion:: This review summarizes the role of chemokines and their receptors in the pathogenesis of RA and also indicates possible interactions of chemokines/receptors with various synthetic and natural compounds that may be used as a potential therapeutic target in the future for the treatment of RA.

Understanding the role of Inflammasome in Angina Pectoris

2020 ◽  
Vol 21 ◽  
Author(s):  
Ishita Sharma ◽  
Tapan Behl ◽  
Simona Bungau ◽  
Monika Sachdeva ◽  
Arun Kumar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Angina Pectoris ◽  
Nlrp3 Inflammasome ◽  
Vital Role ◽  
Death Process ◽  
Cell Death Process ◽  
Artery Disease ◽  
Species Production ◽  
Pro Inflammatory Cytokines

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

scholarly journals Vulnerable Narcissism in Social Networking Sites: The Role of Upward and Downward Social Comparisons

2021 ◽  
Vol 12 ◽  
Author(s):  
Fanchang Kong ◽  
Meiru Wang ◽  
Xingjie Zhang ◽  
Xiaoyao Li ◽  
Xiaojun Sun
Keyword(s):  
Social Networking ◽  
Social Networking Sites ◽  
Social Comparisons ◽  
Vital Role ◽  
Media Effect ◽  
Vulnerable Narcissism ◽  
The Media ◽  
Underlying Mechanisms ◽  
Comparative Theory

Social networking sites (SNSs) have provided a new platform for people to present their narcissism. The objective of the current study was to investigate the underlying mechanisms between active and passive SNS use and vulnerable narcissism among college students. In achieving this, the study based its method on the media effect and social comparative theory and recruited 529 participants to complete the Surveillance Use Scale, Iowa–Netherlands Comparison Orientation Measure, and Hypersensitivity Narcissistic Scale. The results showed that active and passive SNS use were positively related to upward and downward social comparisons. Active and passive SNS use also indirectly predicted vulnerable narcissism through the parallel mediation of upward and downward social comparisons. This study also revealed the vital role of social comparison in the association between SNS use and vulnerable narcissism.

scholarly journals Metformin Corrects Glucose Metabolism Reprogramming and NLRP3 Inflammasome-Induced Pyroptosis via Inhibiting the TLR4/NF-κB/PFKFB3 Signaling in Trophoblasts: Implication for a Potential Therapy of Preeclampsia

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Yang Zhang ◽  
Weifang Liu ◽  
Yanqi Zhong ◽  
Qi Li ◽  
Mengying Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nlrp3 Inflammasome ◽  
Low Dose ◽  
Therapeutic Potential ◽  
Metabolic Phenotypes ◽  
Pyrin Domain ◽  
Underlying Mechanisms ◽  
And Oxidative Stress ◽  
Receptor Family

NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome-mediated pyroptosis is a crucial event in the preeclamptic pathogenesis, tightly linked with the uteroplacental TLR4/NF-κB signaling. Trophoblastic glycometabolism reprogramming has now been noticed in the preeclampsia pathogenesis, plausibly modulated by the TLR4/NF-κB signaling as well. Intriguingly, cellular pyroptosis and metabolic phenotypes may be inextricably linked and interacted. Metformin (MET), a widely accepted NF-κB signaling inhibitor, may have therapeutic potential in preeclampsia while the underlying mechanisms remain unclear. Herein, we investigated the role of MET on trophoblastic pyroptosis and its relevant metabolism reprogramming. The safety of pharmacologic MET concentration to trophoblasts was verified at first, which had no adverse effects on trophoblastic viability. Pharmacological MET concentration suppressed NLRP3 inflammasome-induced pyroptosis partly through inhibiting the TLR4/NF-κB signaling in preeclamptic trophoblast models induced via low-dose lipopolysaccharide. Besides, MET corrected the glycometabolic reprogramming and oxidative stress partly via suppressing the TLR4/NF-κB signaling and blocking transcription factor NF-κB1 binding on the promoter PFKFB3, a potent glycolytic accelerator. Furthermore, PFKFB3 can also enhance the NF-κB signaling, reduce NLRP3 ubiquitination, and aggravate pyroptosis. However, MET suppressed pyroptosis partly via inhibiting PFKFB3 as well. These results provided that the TLR4/NF-κB/PFKFB3 pathway may be a novel link between metabolism reprogramming and NLRP3 inflammasome-induced pyroptosis in trophoblasts. Further, MET alleviates the NLRP3 inflammasome-induced pyroptosis, which partly relies on the regulation of TLR4/NF-κB/PFKFB3-dependent glycometabolism reprogramming and redox disorders. Hence, our results provide novel insights into the pathogenesis of preeclampsia and propose MET as a potential therapy.

scholarly journals The Role of lncRNAs in Regulating the Intestinal Mucosal Mechanical Barrier

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shanshan Chen ◽  
Chi Zhang ◽  
Beihui He ◽  
Ruonan He ◽  
Li Xu ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Pathogenic Bacteria ◽  
Inflammatory Diseases ◽  
Cell Activity ◽  
Chromatin Regulation ◽  
Intestinal Diseases ◽  
Intestinal Environment ◽  
The Stability ◽  
Mechanical Barrier

lncRNA is a transcript that is more than 200 bp in length. Currently, evidence has shown that lncRNA is of great significance in cell activity, involved in epigenetics, gene transcription, chromatin regulation, etc. The existence of an intestinal mucosal mechanical barrier hinders the invasion of pathogenic bacteria and toxins, maintaining the stability of the intestinal environment. Serious destruction or dysfunction of the mechanical barrier often leads to intestinal diseases. This review first summarizes the ability of lncRNAs to regulate the intestinal mucosal mechanical barrier. We then discussed how lncRNAs participate in various intestinal diseases by regulating the intestinal mucosal mechanical barrier. Finally, we envision its potential as a new marker for diagnosing and treating intestinal inflammatory diseases.

On Investigating Energy Stability for Cellular Automata Based PageRank Validation Model in Green Cloud

2019 ◽  
Vol 9 (4) ◽  
pp. 66-85 ◽  
Author(s):  
Arnab Mitra
Keyword(s):  
Cellular Automata ◽  
Environmental Sustainability ◽  
Vital Role ◽  
Energy Stability ◽  
Web Resources ◽  
Computing Model ◽  
Alternative Approach ◽  
Low Energy Consumption ◽  
The Stability

PageRank plays a vital role towards the preparation of the index for web resources. The index is processed by crawling down the relevant websites. Hence, the validation of computed PageRank is crucially significant towards the reliability enhancement of processed indexed list. On the other hand, energy efficiency and the stability of a system are crucially towards the environmental sustainability. In this regard, an energy stability-based PageRank validation model in Cellular Automata is presented in this research which facilitates a very low energy consumption by its physical components. Detailed investigations in view of energy stability explore the role of energy stability towards the validation of PageRank. Hence, an alternative approach towards the validation of PageRank using energy stability is presented in this research. Analytical results obtained with proposed approach for several Clouds further explore its potential capability as a green computing model in the Cloud.

scholarly journals The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yuanyuan Chen ◽  
Ye Zhao ◽  
Qiao Cheng ◽  
Depei Wu ◽  
Haiyan Liu
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Graft Versus Host Disease ◽  
Inflammatory Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Host Immune Responses ◽  
Acute Graft

The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

scholarly journals The factors affecting the bank’s credit impairment losses by adopting IAS on PSAK 55 in Indonesia

2020 ◽  
Vol 22 (3) ◽  
Author(s):  
Sparta Sparta ◽  
Nadya Trinova
Keyword(s):  
Stock Exchange ◽  
Positive Influence ◽  
Vital Role ◽  
Income Smoothing ◽  
Loan Loss ◽  
Factors Affecting ◽  
Loan Loss Provisions ◽  
Ias 39 ◽  
The Stability

Loan loss provisions in banks plays a vital role in maintaining the stability and health of banks, as well as fulfilling the function of banks in channeling public funds. This study aims to determine the effect of income smoothing and the behavior of procyclicality against reserves of credit losses losses, as well as the role of adoption of IAS 39 in PSAK 55 in moderating the influence of these two variables. The object of this study are conventional commercial banks that are listed on the Indonesia Stock Exchange within the research period of 2008-2017. By using purposive sampling method, I obtained 20 bank samples and 196 observations. The hypotheses in this research are tested using multiple regression analysis. This study shows that income smoothing has a positive influence on loan loss provisions, whereas procyclicality and IAS 39 adoption in PSAK 55 do not affect loan loss provisions significantly. Meanwhile, IAS 39 adoption in PSAK 55 weakens the positive influence of income smoothing, however it cannot moderate the influence of procyclicality on loan loss provisions.  

scholarly journals Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6238
Author(s):  
Paromita Sarbadhikary ◽  
Blassan P. George ◽  
Heidi Abrahamse
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
In Vivo Studies ◽  
Inflammasome Activation ◽  
Inflammatory Disorders ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

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