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JOURNAL ARTICLE
Yu-Qing Su, Yan Lin, Shu-Jing Huang, Yan-Ting Lin, Jing Ran, Fang-Fang Yan, Xian-Lan Liu, Long-Cheng Hong, Mei Huang, Huan-Zhong Su, Xiao-Dong Zhang, Jian-Hong You, Yi-Ming Su
We have investigated whether inflammasomes and pyroptosis are activated in maternal nicotine exposure (MNE) offspring mice and whether they are involved in MNE-promoted metabolic associated fatty liver disease (MAFLD) in adult offspring. We injected pregnant mice subcutaneously with saline vehicle or nicotine twice a day on gestational days 11-21. Offspring mice from both groups were fed with a normal diet (ND) or a high-fat diet (HFD) for 6 months at postnatal day 21 to develop the MAFLD model. Serum biochemical indices were analyzed, and liver histology was performed...
November 28, 2023: Molecular Reproduction and Development
#22
JOURNAL ARTICLE
Min Li, Qiuyu Jiang, Xinyi Liu, Liping Han, She Chen, Ruyi Xue
BACKGROUND: Pyroptosis-related genes (PRG) are closely associated with the progression and metastasis of hepatocellular carcinoma (HCC). The predictive power of PRGs could be used to assess the clinical outcomes of HCC. METHODS: The Cancer Genome Atlas (TCGA) RNA-seq data and clinical information from patients with liver hepatocellular carcinoma (LIHC) were used to identify PRG with differentially expressed between HCC and normal samples. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox method, and multivariate Cox regression analysis were used to develop a prognostic model that included three PRGs...
October 12, 2023: Frontiers in Bioscience (Landmark Edition)
#23
JOURNAL ARTICLE
Jian Zou, Rujie Yang, Ruibing Feng, Jiayue Liu, Jian-Bo Wan
Heavy alcohol consumption results in alcoholic liver disease (ALD) with inadequate therapeutic options. Here, we first report the potential beneficial effects of ginsenoside Rk2 (Rk2), a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng, against alcoholic liver injury in mice. Chronic-plus-single-binge ethanol feeding caused severe liver injury, as manifested by significantly elevated serum aminotransferase levels, hepatic histological changes, increased lipid accumulation, oxidative stress, and inflammation in the liver...
September 2023: Journal of Pharmaceutical Analysis
#24
JOURNAL ARTICLE
Jianru Liu, Wenyi Liu, Peiying Lv, Yixiang Wang, Xiangying Ouyang
BACKGROUND/PURPOSE: Gingival epithelial cells form a physiological barrier against bacterial invasion. Programmed cell death (PCD) regulated by pathogen precognition receptors (PRRs) lead to tissue destruction and is closely related to inflammatory diseases. The purpose of this study was to investigate whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 6 (NLRP6) expresses in periodontal epithelium and induces PCD of epithelial cells infected by Porphyromonas gingivalis ( P...
October 2023: Journal of Dental Sciences
#25
JOURNAL ARTICLE
Feng Zhi, Bowen Li, Chuanxia Zhang, Fan Xia, Rong Wang, Weihong Xie, Sihui Cai, Dawei Zhang, Ren Kong, Yiqiao Hu, Yilin Yang, Ya Peng, Jun Cui
The PI3K/AKT pathway plays an essential role in tumour development. NOD-like receptors (NLRs) regulate innate immunity and are implicated in cancer, but whether they are involved in PI3K/AKT pathway regulation is poorly understood. Here, we report that NLRP6 potentiates the PI3K/AKT pathway by binding and destabilizing p85α, the regulatory subunit of PI3K. Mechanistically, NLRP6 recruits the E3 ligase RBX1 to p85α and ubiquitinates lysine 256 on p85α, which is recognized by the autophagy cargo receptor OPTN, causing selective autophagic degradation of p85α and subsequent activation of the PI3K/AKT pathway by reducing PTEN stability...
September 28, 2023: Nature Communications
#26
JOURNAL ARTICLE
Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K Combs, Suba Nookala
Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals...
July 31, 2023: Pathogens
#27
JOURNAL ARTICLE
Min Wang, He Wu, Ronghua Wu, Yongshun Tan, Qingqing Chang
OBJECTIVE: Pyroptosis, a lytic and inflammatory programmed cell death, has been implicated in type 2 diabetes mellitus (T2DM) and its complications. Nonetheless, it remains elusive exactly which pyroptosis molecule exerts an essential role in T2DM, and this study aims to solve such issue. METHODS: Transcriptional profiling datasets of T2DM, i.e., GSE20966, GSE95849, and GSE26168, were acquired. Four machine learning models, namely, random forest, support vector machine, extreme gradient boosting, and generalized linear modeling, were built based on pyroptosis genes...
2023: Frontiers in Endocrinology
#28
REVIEW
Chuan-Han Deng, Tian-Qi Li, Wei Zhang, Qi Zhao, Ying Wang
Inflammasome activation is exclusively involved in sensing activation of innate immunity and inflammatory response during viral infection. Accumulating evidence suggests that the manipulation of inflammasome assembly or its interaction with viral proteins are critical factors in viral pathogenesis. Results from pilot clinical trials show encouraging results of NLRP3 inflammasome suppression in reducing mortality and morbidity in SARS-CoV-2-infected patients. In this article, we summarize the up-to-date understanding of inflammasomes, including NLRP3, AIM2, NLRP1, NLRP6, and NLRC4 in various viral infections, with particular focus on RNA viruses such as SARS-CoV-2, HIV, IAV, and Zika virus and DNA viruses such as herpes simplex virus 1...
June 27, 2023: Viruses
#29
JOURNAL ARTICLE
Sarah Metcalfe, Michelle Panasiewicz, Jason G Kay
Chronic inflammatory periodontal disease develops in part from the infiltration of a large number of classically activated inflammatory macrophages that release inflammatory cytokines important for disease progression, including inflammasome-dependent IL-1β. Streptococcus gordonii is a normally commensal oral microorganism; while not causative, recent evidence indicates that commensal oral microbes are required for the full development of periodontal disease. We have recently reported that inflammatory macrophages counterintuitively allow for the increased survival of phagocytosed S...
July 27, 2023: Journal of Leukocyte Biology
#30
JOURNAL ARTICLE
Hongjin Wang, Nian Wang, Ze Tang, Qiuyu Liu, Shiyu Nie, Wu Tao
BACKGROUND: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC). METHODS: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model...
July 18, 2023: Hereditas
#31
JOURNAL ARTICLE
Liemei Lv, Yu Zhang, Ran Kong, Cong Wang, Xin Wang, Xiangxiang Zhou
PURPOSE: Emerging evidence suggests that pyroptosis plays an essential role in the development and progression of multiple cancers. However, the role of pyroptosis remains elusive in diffuse large B-cell lymphoma (DLBCL). METHODS: The expression profile data of DLBCL and normal samples of pyroptosis-related genes (PRGs) were analyzed, and the clinical characteristics of DLBCL patients were further investigated. A prognostic model was established using LASSO-Cox regression analysis...
July 15, 2023: Journal of Cancer Research and Clinical Oncology
#32
JOURNAL ARTICLE
Francesca Ferrara, Alessandra Pecorelli, Giuseppe Valacchi
SIGNIFICANCE: Inflammasomes are multimeric complexes that, as part of the innate immune response, sense a wide range of pathogenic and sterile stimuli. They consist of three components, namely a sensor protein, an adaptor, and pro-caspase-1 that, once activated, result in secretion of pro-inflammatory interleukin-1β (IL-1β) and IL-18 and, eventually, in a gasdermin D-dependent lytic cell death called pyroptosis. RECENT ADVANCES: Since their discovery 20 years ago, the molecular mechanisms underlying the regulation of inflammasomes have been extensively studied...
July 13, 2023: Antioxidants & Redox Signaling
#33
REVIEW
Liangzheng Chang, Yuying Tian, Lei Xu, Qiuyao Hao, Lingyu Song, Yinying Lu, Yunhuan Zhen
NOD-like receptor family pyrin domain containing 6 (NLRP6) is a new pattern recognition receptor in the mammalian innate immune system. Both the liver and the gut exhibit substantial levels of cytoplasmic expression. It can speed up cell response to endogenous danger signals or exogenous pathogen infection. NLRP6 can function in various ways as an inflammasome or a noninflammasome. The understanding of NLRP6 is steadily increasing thanks to ongoing investigations, but due to discrepancies in how those studies have described their link with tumors, the significance of NLRP6 in the emergence of cancer is still debatable as of this writing...
2023: Journal of Immunology Research
#34
JOURNAL ARTICLE
[Construction of a prognostic model for hepatocellular carcinoma based on pyroptosis-related genes].
H C Rong, W F Zhao, N Zheng, Z H Guo, Y W Wang, X P Huang
Objective: To study the construction of a prognostic model for hepatocellular carcinoma (HCC) based on pyroptosis-related genes (PRGs). Methods: HCC patient datasets were obtained from the Cancer Genome Atlas (TCGA) database, and a prognostic model was constructed by applying univariate Cox and least absolute shrinkages and selection operator (LASSO) regression analysis. According to the median risk score, HCC patients in the TCGA dataset were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox analysis, and nomograms were used to evaluate the predictive ability of the prognostic models...
May 20, 2023: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
#35
JOURNAL ARTICLE
Chuanfeng Tang, Qiaona Wang, Jingyan Shen, Congying Wang, Hong Ding, Shiyu Wen, Fan Yang, Ruiqing Jiao, Xingxin Wu, Jianmei Li, Lingdong Kong
Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout ( Nlrp6 -/- ) and NSC-conditional Nlrp6 knockout ( Nlrp6 CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors...
May 2023: Acta Pharmaceutica Sinica. B
#36
REVIEW
Katherine C Barnett, Sirui Li, Kaixin Liang, Jenny P-Y Ting
Inflammasomes are critical sentinels of the innate immune system that respond to threats to the host through recognition of distinct molecules, known as pathogen- or damage-associated molecular patterns (PAMPs/DAMPs), or disruptions of cellular homeostasis, referred to as homeostasis-altering molecular processes (HAMPs) or effector-triggered immunity (ETI). Several distinct proteins nucleate inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRC4/NAIP, AIM2, pyrin, and caspases-4/-5/-11. This diverse array of sensors strengthens the inflammasome response through redundancy and plasticity...
May 25, 2023: Cell
#37
JOURNAL ARTICLE
Dan Jian, Le Qin, Hui Gan, Shuyue Zheng, Han Xiao, Yuhao Duan, Mi Zhang, Ping Liang, Jing Zhao, Xuan Zhai
Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11...
May 5, 2023: International Journal of Molecular Sciences
#38
JOURNAL ARTICLE
Xinyi Chen, Mu Yang, Lu Wang, Yuan Wang, Jingyao Tu, Xiao Zhou, Xianglin Yuan
We used pyroptosis-related genes to establish a risk-score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA database. Through gene expression analyses, differentially expressed genes (DEGs) were determined. The 13 pyroptosis-related genes (PRGs) confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a PRGs prognostic signature, containing four PRGs (BAK1, GSDME, NLRP6, and NOD2) determined as independent prognostic factors...
May 6, 2023: BMC Cancer
#39
JOURNAL ARTICLE
Hao Yu Chen, Christian Dina, Aeron M Small, Christian M Shaffer, Rebecca T Levinson, Anna Helgadóttir, Romain Capoulade, Hans Markus Munter, Andreas Martinsson, Benjamin J Cairns, Linea C Trudsø, Mary Hoekstra, Hannah A Burr, Thomas W Marsh, Scott M Damrauer, Line Dufresne, Solena Le Scouarnec, David Messika-Zeitoun, Dilrini K Ranatunga, Rachel A Whitmer, Amélie Bonnefond, Garðar Sveinbjornsson, Ragnar Daníelsen, David O Arnar, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Daníel F Gudbjartsson, Hilma Hólm, Jonas Ghouse, Morten Salling Olesen, Alex H Christensen, Susan Mikkelsen, Rikke Louise Jacobsen, Joseph Dowsett, Ole Birger Vesterager Pedersen, Christian Erikstrup, Sisse R Ostrowski, Christopher J O'Donnell, Matthew J Budoff, Vilmundur Gudnason, Wendy S Post, Jerome I Rotter, Mark Lathrop, Henning Bundgaard, Bengt Johansson, Johan Ljungberg, Ulf Näslund, Thierry Le Tourneau, J Gustav Smith, Quinn S Wells, Stefan Söderberg, Kári Stefánsson, Jean-Jacques Schott, Daniel J Rader, Robert Clarke, James C Engert, George Thanassoulis
AIMS: Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. METHODS AND RESULTS: A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2...
April 11, 2023: European Heart Journal
#40
JOURNAL ARTICLE
Xinzhe Lou, Jianru Liu, Xiangying Ouyang, Wenyi Liu, Ying Xie, Jinsheng Zhong, Peiying Lv, Shengnan Zhang
BACKGROUND/PURPOSE: Porphyromonas gingivalis (P. gingivalis ) could induce the activation of vascular endothelial cells and promote the formation of atherosclerosis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing (NLRP) 6 could recognize P. gingivalis, but its role in atherosclerosis was unknown. The purpose of this study is to investigate the role of NLRP6 in the activation of inflammation in human umbilical vein endothelial cells (HUVECs) stimulated by P...
April 2023: Journal of Dental Sciences
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