Global trends and prospects about inflammasomes in stroke: a bibliometric analysis

Abstract Background Sterile inflammation is a key pathological process in stroke. Inflammasome activation has been implicated in various inflammatory diseases, including ischemic stroke and hemorrhagic stroke. Hence, targeting inflammasomes is a promising approach for the treatment of stroke. Methods We applied bibliometric methods and techniques. The Web of Science Core Collection was searched for studies indexed from database inception to November 26, 2020. We generated various visual maps to display publications, authors, sources, countries, and keywords. Results Our literature search yielded 427 publications related to inflammasomes involved in stroke, most of which consisted of original research articles and reviews. In particular, we found that there was a substantial increase in the number of relevant publications in 2018. Furthermore, most of the publications with the highest citation rates were published in 2014. Relatively, the field about inflammasomes in stroke developed rapidly in 2014 and 2018. Many institutions contributed to these publications, including those from China, the United States, and worldwide. We found that NLR family pyrin domain containing 3 (NLRP3) was the most studied, followed by NLRP1, NLRP2, and NLRC4 among the inflammasomes associated with stroke. Analysis of keywords suggested that the most studied mechanisms involved dysregulation of extracellular pH, efflux of Ca2+ ions, dysfunction of K+/Na+ ATPases, mitochondrial dysfunction, and damage to mitochondrial DNA. Conclusions Given the potential diagnostic and therapeutic implications, the specific mechanisms of inflammasomes contributing to stroke warrant further investigation. We used bibliometric methods to objectively present the global trend of inflammasomes in stroke, and to provide important information for relevant researchers.

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LRR protein RNH1 inhibits inflammasome activation through proteasome-mediated degradation of Caspase-1 and is associated with adverse clinical outcomes in COVID-19 patients.

10.1101/2021.04.12.438219 ◽

2021 ◽

Author(s):

Giuseppe Bombaci ◽

Mayuresh A Sarangdhar ◽

Nicola Andina ◽

Aubry Tardivel ◽

Eric Chi-Wang Yu ◽

...

Keyword(s):

Inflammatory Diseases ◽

Neutrophil Infiltration ◽

Inflammasome Activation ◽

Ribonuclease Inhibitor ◽

Protein Levels ◽

Caspase 1 ◽

Pyrin Domain ◽

Underlying Mechanisms ◽

Lrr Protein ◽

Receptor Family

Inflammasomes are cytosolic innate immune sensors that, upon activation, induce caspase-1 mediated inflammation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and is also detrimental in COVID-19 infection. However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine rich repeat (LRR) protein Ribonuclease inhibitor (RNH1), which shares homology with LRRs of NOD-like receptor family pyrin domain (PYD)-containing (NLRP) proteins, attenuates inflammasome activation. Mechanistically, RNH1 decreased pro-IL1b expression and induced proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and LPS-induced endotoxemia, which are dependent on caspase-1, respectively showed increased neutrophil infiltration and lethality in Rnh1-/- mice compared to WT mice. Further, RNH1 protein levels were negatively correlated with inflammation and disease severity in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.

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Sinapic Acid Controls Inflammation by Suppressing NLRP3 Inflammasome Activation

Cells ◽

10.3390/cells10092327 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2327

Author(s):

Eun Hye Lee ◽

Jin Hak Shin ◽

Seon Sook Kim ◽

Su Ryeon Seo

Keyword(s):

Cinnamic Acid ◽

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

Endotoxic Shock ◽

Sinapic Acid ◽

Inflammasome Activation ◽

Cinnamic Acid Derivative ◽

Pyrin Domain ◽

Nlrp3 Inflammasome Activation ◽

Anti Inflammatory

A natural phenolic acid compound, sinapic acid (SA), is a cinnamic acid derivative that contains 3,5-dimethoxyl and 4-hydroxyl substitutions in the phenyl ring of cinnamic acid. SA is present in various orally edible natural herbs and cereals and is reported to have antioxidant, antitumor, anti-inflammatory, antibacterial, and neuroprotective activities. Although the anti-inflammatory function of SA has been reported, the effect of SA on the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has not been explored. In the present study, to elucidate the anti-inflammatory mechanism of SA, we examined whether SA modulates the NLRP3 inflammasome. We found that SA blocked caspase-1 activation and IL-1β secretion by inhibiting NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs). Apoptosis-associated speck-like protein containing CARD (ASC) pyroptosome formation was consistently blocked by SA treatment. SA specifically inhibited NLRP3 activation but not the NLRC4 or AIM2 inflammasomes. In addition, SA had no significant effect on the priming phase of the NLRP3 inflammasome, such as pro-IL-1β and NLRP3 inflammasome expression levels. Moreover, we found that SA attenuated IL-1β secretion in LPS-induced systemic inflammation in mice and reduced lethality from endotoxic shock. Our findings suggest that the natural compound SA has potential therapeutic value for the suppression of NLRP3 inflammasome-associated inflammatory diseases.

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NLRP3 inflammasome is involved in uterine activation for labor at term and preterm

Reproduction ◽

10.1530/rep-21-0047 ◽

2021 ◽

Vol 162 (6) ◽

pp. 449-460

Author(s):

Zixi Chen ◽

Yali Shan ◽

Xingji You ◽

Hang Gu ◽

Chen Xu ◽

...

Keyword(s):

Mouse Model ◽

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

Critical Role ◽

Inflammasome Activation ◽

Pyrin Domain ◽

Nlrp3 Inflammasome Activation ◽

Pregnant Mice ◽

Labor Onset

The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.

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Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases

Science Immunology ◽

10.1126/sciimmunol.abe2933 ◽

2021 ◽

Vol 6 (58) ◽

pp. eabe2933

Author(s):

Guang-Ming Ren ◽

Jian Li ◽

Xiao-Chun Zhang ◽

Yu Wang ◽

Yang Xiao ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

Therapeutic Benefit ◽

Inflammasome Activation ◽

Therapeutic Effects ◽

Autoimmune Encephalomyelitis ◽

Deficient Diet ◽

Nonalcoholic Fatty Liver ◽

Pyrin Domain ◽

Nlrp3 Inflammasome Activation

Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate–induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline–deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)–mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.

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NLRP3 Inflammasome-Mediated Inflammation in Acute Pancreatitis

International Journal of Molecular Sciences ◽

10.3390/ijms21155386 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5386 ◽

Cited By ~ 1

Author(s):

Ana Ferrero-Andrés ◽

Arnau Panisello-Roselló ◽

Joan Roselló-Catafau ◽

Emma Folch-Puy

Keyword(s):

Acute Pancreatitis ◽

Nlrp3 Inflammasome ◽

Inflammatory Diseases ◽

Interleukin 1 ◽

Pancreatic Injury ◽

Inflammasome Activation ◽

Inflammatory Disorder ◽

Pyrin Domain ◽

Current State ◽

Nlrp3 Inflammasome Activation

The discovery of inflammasomes has enriched our knowledge in the pathogenesis of multiple inflammatory diseases. The NLR pyrin domain-containing protein 3 (NLRP3) has emerged as the most versatile and well-characterized inflammasome, consisting of an intracellular multi-protein complex that acts as a central driver of inflammation. Its activation depends on a tightly regulated two-step process, which includes a wide variety of unrelated stimuli. It is therefore not surprising that the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Inflammasome-mediated inflammation has become increasingly important in acute pancreatitis, an inflammatory disorder of the pancreas that is one of the fatal diseases of the gastrointestinal tract. This review presents an update on the progress of research into the contribution of the NLRP3 inflammasome to acute pancreatic injury, examining the mechanisms of NLRP3 activation by multiple signaling events, the downstream interleukin 1 family of cytokines involved and the current state of the literature on NLRP3 inflammasome-specific inhibitors.

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Utopias of One

10.23943/princeton/9780691196541.001.0001 ◽

2019 ◽

Author(s):

Joshua Kotin

Keyword(s):

United States ◽

Soviet Union ◽

World War I ◽

Large Scale ◽

Jim Crow ◽

Personal Autonomy ◽

The United States ◽

Soviet Period ◽

Original Research ◽

The Soviet Union

This book is a new account of utopian writing. It examines how eight writers—Henry David Thoreau, W. E. B. Du Bois, Osip and Nadezhda Mandel'shtam, Anna Akhmatova, Wallace Stevens, Ezra Pound, and J. H. Prynne—construct utopias of one within and against modernity's two large-scale attempts to harmonize individual and collective interests: liberalism and communism. The book begins in the United States between the buildup to the Civil War and the end of Jim Crow; continues in the Soviet Union between Stalinism and the late Soviet period; and concludes in England and the United States between World War I and the end of the Cold War. In this way it captures how writers from disparate geopolitical contexts resist state and normative power to construct perfect worlds—for themselves alone. The book contributes to debates about literature and politics, presenting innovative arguments about aesthetic difficulty, personal autonomy, and complicity and dissent. It models a new approach to transnational and comparative scholarship, combining original research in English and Russian to illuminate more than a century and a half of literary and political history.

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Global Trends in the Political Economy of Smart Grids

10.1093/oso/9780198802242.003.0017 ◽

2017 ◽

Cited By ~ 2

Author(s):

Cherrelle Eid ◽

Rudi Hakvoort ◽

Martin de Jong

Keyword(s):

Smart Grid ◽

Smart Grids ◽

The United States ◽

Industry Structure ◽

Electricity Sector ◽

Distributed Energy ◽

Global Trends ◽

Political Economic ◽

Regulatory Models ◽

Global Transition

The global transition towards sustainable, secure, and affordable electricity supply is driving changes in the consumption, production, and transportation of electricity. This chapter provides an overview of three main causes of political–economic tensions with smart grids in the United States, Europe, and China, namely industry structure, regulatory models, and the impact of energy policy. In all cases, the developments are motivated by the possible improvements in reliability and affordability yielded by smart grids, while sustainability of the electricity sector is not a central motivation. A holistic smart grid vision would open up possibilities for better integration of distributed energy resources. The authors recommend that smart grid investments should remain outside of the regulatory framework for utilities and distribution service operators in order to allow for such developments.

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8.I. Workshop: Populist radical right and health: National policies and global trends

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.406 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

◽

Keyword(s):

Public Health ◽

United States ◽

Welfare State ◽

The United States ◽

Radical Right ◽

Health Policies ◽

National Policies ◽

Global Trends ◽

Populist Radical Right ◽

The Welfare State

Abstract Populist radical right (PRR) parties have been steadily expanding, not only in the number of supporters they gain and the seats they win in governments, but more importantly they have been increasingly elected into governmental coalitions as well as presidential offices. With the prominence of these authoritarian, nationalistic and populist parties, it is often difficult to discern what kind of policies they actually stand for. Particularly with regards to the welfare state and public health, it is not always clear what these parties stand for. At times they call for a reduction of health-related welfare provision, despite the fact that this goes against the will of the “ordinary people”, their core supporters; they often promote radical reductions of welfare benefits among socially excluded groups - usually immigrants, whom are most in need of such services; and finally they often mobilize against evidence-based policies. The purpose of this workshop is to present the PRRs actual involvement in health care and health policies across various countries. As PRR parties increase and develop within but also outside of the European continent it is necessary to keep track of their impact, particularly with regards to health and social policies. Although research surrounding PRR parties has significantly expanded over the last years, their impact on the welfare state and more specifically health policies still remains sparse. This workshop will present findings from the first comprehensive book connecting populist radical right parties with actual health and social policy effects in Europe (Eastern and Western) as well as in the United States. This workshop presents five country cases (Austria, Poland, the Netherlands, the United States) from the book Populist Radical Right and Health: National Policies and Global Trends. All five presentations will address PRR parties or leaders and their influence on health, asking the questions “How influential are PRR parties or leaders when it comes to health policy?” “Do the PRR actually have an impact on policy outcomes?” and “What is the actual impact of the health policies implemented by PRR parties or leaders?” After these five presentations, the participants of the workshop will be engaged in an interactive discussion. Key messages As the number of PRR parties increase worldwide and their involvement in national governments become inevitable, new light must be shed on the impact these political parties have on public health. Politics needs to become better integrated into public health research. The rise of PRR parties in Europe might have serious consequences for public health and needs to be further explored.

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Aggregated Tau-PHF6 (VQIVYK) Potentiates NLRP3 Inflammasome Expression and Autophagy in Human Microglial Cells

Cells ◽

10.3390/cells10071652 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1652

Author(s):

Chinmaya Panda ◽

Clara Voelz ◽

Pardes Habib ◽

Christian Mevissen ◽

Thomas Pufe ◽

...

Keyword(s):

Tau Protein ◽

Nlrp3 Inflammasome ◽

Time Dependent ◽

Microglial Cells ◽

Inflammasome Activation ◽

Dependent Manner ◽

Progressive Dementia ◽

Microglial Polarization ◽

Protein Levels ◽

Pyrin Domain

Intra-neuronal misfolding of monomeric tau protein to toxic β-sheet rich neurofibrillary tangles is a hallmark of Alzheimer’s disease (AD). Tau pathology correlates not only with progressive dementia but also with microglia-mediated inflammation in AD. Amyloid-beta (Aβ), another pathogenic peptide involved in AD, has been shown to activate NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3), triggering the secretion of proinflammatory interleukin-1β (IL1β) and interleukin-18 (IL18). However, the effect of tau protein on microglia concerning inflammasome activation, microglial polarization, and autophagy is poorly understood. In this study, human microglial cells (HMC3) were stimulated with the unaggregated and aggregated forms of the tau-derived PHF6 peptide (VQIVYK). Modulation of NLRP3 inflammasome was examined by qRT-PCR, immunocytochemistry, and Western blot. We demonstrate that fibrillar aggregates of VQIVYK upregulated the NLRP3 expression at both mRNA and protein levels in a dose- and time-dependent manner, leading to increased expression of IL1β and IL18 in HMC3 cells. Aggregated PHF6-peptide also activated other related inflammation and microglial polarization markers. Furthermore, we also report a time-dependent effect of the aggregated PHF6 on BECN1 (Beclin-1) expression and autophagy. Overall, the PHF6 model system-based study may help to better understand the complex interconnections between Alzheimer’s PHF6 peptide aggregation and microglial inflammation, polarization, and autophagy.

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Standing on the shoulders of Giants: a citation analysis of the paediatric congenital heart disease literature

Cardiology in the Young ◽

10.1017/s1047951121001256 ◽

2021 ◽

pp. 1-9

Author(s):

Daniel P. Sew ◽

Nigel E. Drury

Keyword(s):

Citation Analysis ◽

San Francisco ◽

Citation Count ◽

Case Series ◽

Scientific Progress ◽

The United States ◽

Original Research ◽

Prolific Author ◽

Journal Citation Reports ◽

The Impact

Abstract Objective: The citation history of a published article reflects its impact on the literature over time. We conducted a comprehensive bibliometric analysis to identify the most cited papers on CHD in children. Methods: One-hundred and ninety journals listed in Journal Citation Reports were accessed via Web of Science. Publications with 250 or more citations were identified from Science Citation Index Expanded (1900–2020), and those relating to structural CHD in children were reviewed. Articles were ranked by citation count and the 100 most cited were analysed. Results: The number of citations ranged from 2522 to 309 (median 431, IQR 356–518), with 35 published since 2000. All were written in English, most originated from the United States (74%), and were published in cardiovascular journals, with Circulation (28%) the most frequent. There were 86 original research articles, including 50 case series, 14 cohort studies, and 10 clinical trials. The most cited paper was by Hoffman JI and Kaplan S on the incidence of CHD. Thirteen authors had 4 or more publications in the top 100, all of whom had worked in Boston, Philadelphia, San Francisco, or Dallas, and the most prolific author was Newburger JW (9 articles). Conclusions: Citation analysis provides a historical perspective on scientific progress by assessing the impact of individual articles. Our study highlights the dominant position of US-based researchers and journals in this field. Most of the highly cited articles remain case series, with few randomised controlled trials in CHD appearing in recent years.

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