keyword
https://read.qxmd.com/read/38528718/the-cytoplasmic-sensor-the-aim2-inflammasome-a-precise-therapeutic-target-in-vascular-and-metabolic-diseases
#1
REVIEW
Jiuguo Lin, Jiaojiao Wang, Jian Fang, Meihang Li, Suowen Xu, Peter J Little, Dongmei Zhang, Zhiping Liu
Cardio-cerebrovascular diseases encompass pathological changes in the heart, brain and vascular system, which pose a great threat to health and well-being worldwide. Moreover, metabolic diseases contribute to and exacerbate the impact of vascular diseases. Inflammation is a complex process that protects against noxious stimuli but is also dysregulated in numerous so-called inflammatory diseases, one of which is atherosclerosis. Inflammation involves multiple organ systems and a complex cascade of molecular and cellular events...
March 25, 2024: British Journal of Pharmacology
https://read.qxmd.com/read/38488012/disassembly-of-the-trim56-atr-complex-promotes-cytodna-cgas-sting-axis-dependent-intervertebral-disc-inflammatory-degeneration
#2
JOURNAL ARTICLE
Weifeng Zhang, Gaocai Li, Xingyu Zhou, Huaizhen Liang, Bide Tong, Di Wu, Kevin Yang, Yu Song, Bingjin Wang, Zhiwei Liao, Liang Ma, Wencan Ke, Xiaoguang Zhang, Jie Lei, Chunchi Lei, Xiaobo Feng, Kun Wang, Kangcheng Zhao, Cao Yang
As the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socioeconomic challenge to the aging population and is largely attributed to intervertebral disc degeneration (IVDD). Elastic nucleus pulposus (NP) tissue is essential for the maintenance of IVD structural and functional integrity. The accumulation of senescent NP cells with an inflammatory hypersecretory phenotype due to aging and other damaging factors is a distinctive hallmark of IVDD initiation and progression. In this study, we reveal a mechanism of IVDD progression in which aberrant genomic DNA damage promoted NP cell inflammatory senescence via activation of the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) axis but not of absent in melanoma 2 (AIM2) inflammasome assembly...
January 23, 2024: Journal of Clinical Investigation
https://read.qxmd.com/read/38487102/clustering-human-dental-pulp-fibroblasts-spontaneously-activate-nlrp3-and-aim2-inflammasomes-and-induce-il-1%C3%AE-secretion
#3
JOURNAL ARTICLE
Shafei Zhai, Lihui Zhang, Xue Li, Qi Yu, Changkui Liu
OBJECTIVES: The objective of the present study was to investigate whether NOD-like receptor family pyrin domain-containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes pathways were involved in an experimental model of fibroblast activation named nemosis, which was used to mimic circumstances without bacteria stimulation. METHODS: Nemosis of human dental pulp fibroblast (DPFs) was induced by three-dimensional culture in U-shaped 96-well plates and investigated by scanning electron microscopy (SEM)...
December 2024: Regenerative Therapy
https://read.qxmd.com/read/38476473/identification-and-validation-of-genes-related-to-macrophage-polarization-and-cell-death-modes-under-mycobacterium-tuberculosis-infection
#4
JOURNAL ARTICLE
Zisha Yang, Jiajun Wang, Jiang Pi, Di Hu, Junfa Xu, Yi Zhao, Yan Wang
PURPOSE: To investigate the correlation between M1/M2 macrophages (M1/M2 Mφ) and cell death mode under Mycobacterium tuberculosis (Mtb) infection. METHODS: Raw gene expression profiles were collected from the Gene Expression Omnibus (GEO) database. Genes related to different cell death modes were collected from the KEGG, FerrDb and GSEA databases. The differentially expressed genes (DEGs) of the gene expression profiles were identified using the limma package in R...
2024: Journal of Inflammation Research
https://read.qxmd.com/read/38470107/activation-of-the-lysosomal-damage-response-and-selective-autophagy-the-coordinated-actions-of-galectins-trim-proteins-and-cgas-sting1-in-providing-immunity-against-mycobacterium-tuberculosis
#5
REVIEW
Asrar Ahmad Malik, Mohd Shariq, Javaid Ahmad Sheikh, Sheeba Zarin, Yashika Ahuja, Haleema Fayaz, Anwar Alam, Nasreen Z Ehtesham, Seyed E Hasnain
Autophagy is a crucial immune defense mechanism that controls the survival and pathogenesis of M. tb by maintaining cell physiology during stress and pathogen attack. The E3-Ub ligases (PRKN, SMURF1, and NEDD4) and autophagy receptors (SQSTM1, TAX1BP1, CALCOCO2, OPTN, and NBR1) play key roles in this process. Galectins (LGALSs), which bind to sugars and are involved in identifying damaged cell membranes caused by intracellular pathogens such as M. tb , are essential. These include LGALS3, LGALS8, and LGALS9, which respond to endomembrane damage and regulate endomembrane damage caused by toxic chemicals, protein aggregates, and intracellular pathogens, including M...
March 12, 2024: Critical Reviews in Microbiology
https://read.qxmd.com/read/38468925/cyclin-dependent-kinase-inhibitor-1a-inhibits-pyroptosis-to-enhance-human-lung-adenocarcinoma-cell-radioresistance-by-promoting-dna-repair
#6
JOURNAL ARTICLE
Jing Li, Teng Liu, Ning Tang, Sheng Lin, Feng Zhang, Wei Yuan, Ting Zhang, Shi-Hua Deng, Dong-Ming Wu, Ying Xu
PURPOSE: One of the best anticancer treatments available is radiotherapy, which can be used either alone or in conjunction with other forms of treatment including chemotherapy and surgery. Nevertheless, a number of biochemical and physiological processes that react to ionizing radiation might provide tumor cells radioresistance, which makes radiotherapy ineffective. It has been found that CDKN1A regulates DNA damage repair, which contributes to tumor radioresistance. However, the precise mechanism is still unknown...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38467968/mitochondrial-damage-and-clearance-in-retinal-pigment-epithelial-cells
#7
JOURNAL ARTICLE
Iswariyaraja Sridevi Gurubaran
Age-related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing-associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation...
March 2024: Acta Ophthalmologica
https://read.qxmd.com/read/38466568/autophagy-inhibition-induced-cytosolic-dna-sensing-combined-with-differentiation-therapy-induces-irreversible-myeloid-differentiation-in-leukemia-cells
#8
JOURNAL ARTICLE
Tomohisa Baba, Utano Tomaru, Atsushi Hirao, Naofumi Mukaida, Yoshikazu Johmura
Accumulating evidence indicates that various oncogenic mutations interfere with normal myeloid differentiation of leukemogenic cells during the early process of acute myeloid leukemia (AML) development. Differentiation therapy is a therapeutic strategy capable of terminating leukemic expansion by reactivating the differentiation potential; however, the plasticity and instability of leukemia cells counteract the establishment of treatments aimed at irreversibly inducing and maintaining their differentiation states...
March 11, 2024: Cancer Res Commun
https://read.qxmd.com/read/38462200/polystyrene-nanoplastics-and-cadmium-co-exposure-aggravated-cardiomyocyte-damage-in-mice-by-regulating-panoptosis-pathway
#9
JOURNAL ARTICLE
Jiali Ye, Wenyue Qiu, Xiaoyue Pang, Yiman Su, Xinting Zhang, Jianjia Huang, Haoming Xie, Jianzhao Liao, Zhaoxin Tang, Zefeng Chen, Fei Li, Zhaojun Xiong, Rongsheng Su
Micro/nanoplastics (M/NPs) are the novel contaminants ubiquitous in the environment. Cadmium (Cd), a kind of heavy metal pollutant widely distributed, could potentially co-exist with PS-NPs in the environment. However, their combined effects on cardiomyocyte and its molecular mechanism in mammals remained ambiguous. Here, we examined whether PANoptosis, an emerging and complicated kind of programmed cell death, was involved in PS-NPs and Cd co-exposure-elicited cardiac injury. In this study, 60 male mice were orally subjected to environmentally relevant concentrations of PS-NPs (1 mg/kg) and/or CdCl2 (1...
March 8, 2024: Environmental Pollution
https://read.qxmd.com/read/38460301/the-activation-of-the-aim2-inflammasome-after-cigarette-smoke-exposure-leads-to-an-immunosuppressive-lung-microenvironment
#10
JOURNAL ARTICLE
Chiara Colarusso, Anna Falanga, Simone Di Caprio, Michela Terlizzi, Aldo Pinto, Piera Maiolino, Rosalinda Sorrentino
Cigarette smoke is widely known as contributing to chronic inflammation underlying several airway diseases, such as chronic obstructive pulmonary disease (COPD) and lung cancer. In our previous studies we found that the lung of both COPD and cancer patients were characterized by the presence and activation of the AIM2 inflammasome. Here, we wanted to investigate the upstream step during the establishment of chronic lung inflammation after cigarette smoke exposure. We took advantage of a mouse model of smoking exposure and public scRNAseq data...
March 8, 2024: International Immunopharmacology
https://read.qxmd.com/read/38455135/identification-and-validation-of-a-pyroptosis-related-prognostic-model-for-colorectal-cancer-based-on-bulk-and-single-cell-rna-sequencing-data
#11
JOURNAL ARTICLE
Li-Hua Zhu, Jun Yang, Yun-Fei Zhang, Li Yan, Wan-Rong Lin, Wei-Qing Liu
BACKGROUND: Pyroptosis impacts the development of malignant tumors, yet its role in colorectal cancer (CRC) prognosis remains uncertain. AIM: To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration. METHODS: Gene expression data were obtained from The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus (GEO). Pyroptosis-related gene expression in cell clusters was analyzed, and enrichment analysis was conducted...
February 24, 2024: World Journal of Clinical Oncology
https://read.qxmd.com/read/38429284/aim2-regulates-autophagy-to-mitigate-oxidative-stress-in-aged-mice-with-acute-liver-injury
#12
JOURNAL ARTICLE
Chao Hu, Mengjing Li, Yongzhen Chen, Wei Cheng, Haining Wang, Yiming Zhou, Fengmeng Teng, Tao Ling, Jinshun Pan, Haozhe Xu, Yanan Zheng, Guozhong Ji, Ting Zhao, Qiang You
The cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2's contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2's novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation...
March 1, 2024: Cell Death Discovery
https://read.qxmd.com/read/38428714/lipopolysaccharide-induced-intestinal-inflammation-on-aim2-mediated-pyroptosis-in-the-brain-of-rats-with-cerebral-small-vessel-disease
#13
JOURNAL ARTICLE
Huiping Xu, Han Xiao, Qiqiang Tang
Cerebral small vessel disease (CSVD) is a cerebral vascular disease with insidious onset and poor clinical treatment effect, the disease is related to neuroinflammation. This study investigated whether lipopolysaccharide-induced intestinal inflammation enhanced the level of pyroptosis in the brain of rats with CSVD. The bilateral carotid artery occlusion (BCAO) model was selected as the object of study. Firstly, behavioral tests and Hematoxylin-eosin staining (HE staining) were performed to determine whether the model was successful, and then AIM2-mediated inflammasome and pyroptosis indexes(GSDMD、N-GSDMD)in brain tissue were detected by Western blotting and Immunohistochemistry...
February 28, 2024: Experimental Neurology
https://read.qxmd.com/read/38408849/interrupting-an-ifn-%C3%AE-dependent-feedback-loop-in-the-syndrome-of-pyogenic-arthritis-with-pyoderma-gangrenosum-and-acne
#14
JOURNAL ARTICLE
Wonyong Lee, Deborah L Stone, Patrycja Hoffmann, Sofia Rosenzweig, Wanxia Li Tsai, Massimo Gadina, Tina Romeo, Chyi-Chia Richard Lee, Davide Randazzo, Pallavi Pimpale Chavan, Kalpana Manthiram, Scott Canna, Yong Hwan Park, Amanda K Ombrello, Ivona Aksentijevich, Daniel L Kastner, Jae Jin Chae
OBJECTIVES: To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in PSTPIP1 . METHODS: Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation...
February 26, 2024: Annals of the Rheumatic Diseases
https://read.qxmd.com/read/38402873/identification-of-pyroptosis-related-genes-regulating-the-progression-of-chronic-rhinosinusitis-with-nasal-polyps
#15
JOURNAL ARTICLE
Danyang Li, Jisheng Zhang, Lin Wang, Xudong Yan, Jiajia Zi, Xiaoyun Du, Longgang Yu, Yan Jiang
INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an immunologic disease, and pyroptosis, an inflammation-based cellular death, strictly modulates CRSwNP pathology, whereas the pyroptosis genes and mechanisms involved in CRSwNP remain unclear. Herein, we explored disease biomarkers and potential therapeutic targets for pyroptosis and immune regulation in CRSwNP using bioinformatics analysis and tissue-based verification. METHODS: We retrieved the transcriptional profiles of the high-throughput dataset GSE136825 from the Gene Expression Omnibus database, as well as 170 pyroptosis-related gene expressions from GeneCards...
February 23, 2024: International Archives of Allergy and Immunology
https://read.qxmd.com/read/38391935/the-bk-channel-limits-the-pro-inflammatory-activity-of-macrophages
#16
JOURNAL ARTICLE
Yihe Chen, Nikita Markov, Lea Gigon, Aref Hosseini, Shida Yousefi, Darko Stojkov, Hans-Uwe Simon
Macrophages play a crucial role in the innate immune response, serving as key effector cells in the defense against pathogens. Although the role of the large-conductance voltage and calcium-activated potassium channel, also known as the KCa 1.1 or BK channel, in regulating neurotransmitter release and smooth muscle contraction is well known, its potential involvement in immune regulation remains unclear. We employed BK-knockout macrophages and noted that the absence of a BK channel promotes the polarization of macrophages towards a pro-inflammatory phenotype known as M1 macrophages...
February 9, 2024: Cells
https://read.qxmd.com/read/38387757/revitalizing-antitumor-immunity-leveraging-nucleic-acid-sensors-as-therapeutic-targets
#17
REVIEW
Dan-Feng Liu, Wei He, Lei-Lei Yang
Nucleic acid sensors play a critical role in recognizing and responding to pathogenic nucleic acids as danger signals. Upon activation, these sensors initiate downstream signaling cascades that lead to the production and release of pro-inflammatory cytokines, chemokines, and type I interferons. These immune mediators orchestrate diverse effector responses, including the activation of immune cells and the modulation of the tumor microenvironment. However, careful consideration must be given to balancing the activation of nucleic acid sensors to avoid unwanted autoimmune or inflammatory responses...
February 20, 2024: Cancer Letters
https://read.qxmd.com/read/38385899/correlation-between-double-stranded-dna-and-acute-urticaria
#18
JOURNAL ARTICLE
Yuanyuan Li, Zhuo Li, Jiayi Lu, Guangbo Qu, Qin Qin, Chang Zhang, Yuanming Bai, Daiyue Wang, Sihan Luo, Bao Li, Yang Han, Weiwei Chen, Qi Zhen, Liangdan Sun
BACKGROUND: Acute urticaria is a prevalent inflammatory dermatosis characterized by fulminant wheals, often accompanied by severe pruritis. It may also cause nausea, vomiting, and abdominal pain. Numerous studies have substantiated the pivotal involvement of double-stranded DNA (dsDNA) in autoimmunity. However, the role of dsDNA in the pathogenesis of acute urticaria is unclear. METHODS: We measured serum dsDNA levels in patients and controls. The relationship between dsDNA levels and environmental exposures (temperature, ultraviolet [UV] index, and season) was investigated by correlating disease onset dates with archived meteorological data...
February 22, 2024: International Journal of Dermatology
https://read.qxmd.com/read/38380569/e-globulus-leaf-eo-exhibits-anti-inflammatory-effects-by-regulating-gsdmd-mediated-pyroptosis-thereby-alleviating-neurological-impairment-and-neuroinflammation-in-experimental-stroke-mice
#19
JOURNAL ARTICLE
Dexiao Wang, Zhengmei Shi, Chaojie Liu, Qian Wang, Heng Liu, Junli He, Hairong Zhao, Chenggui Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Aromatic and medicinal plants continue to be a major component of alternative and traditional medicine in the developing countries. Eucalyptus globulus (Labill.) is being employed to cultivation and production in China. However, few studies have reported the chemical composition and anti-inflammatory activity of Eucalyptus globulus (Labill.) leaf essential oil (E. globulus leaf EO) extracted from Eucalyptus globulus. AIM OF THE STUDY: This study aimed to assess the composition of E...
January 30, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38356604/crocin-attenuates-the-lipopolysaccharide-induced-neuroinflammation-via-expression-of-aim2-and-nlrp1-inflammasome-in-an-experimental-model-of-parkinson-s-disease
#20
JOURNAL ARTICLE
Solmaz Alizadehmoghaddam, Fereshteh Pourabdolhossein, Hossein Najafzadehvarzi, Maryam Sarbishegi, Kiarash Saleki, Hamid Reza Nouri
The underlying mechanisms of inflammasome activation and the following dopaminergic neuron loss caused by chronic neuroinflammation remain entirely unclear. Therefore, this study aimed to investigate the impact of crocin on the inflammasome complex within an experimental model of Parkinson's disease (PD) using male Wistar rats. PD was induced by the stereotaxic injection of lipopolysaccharide (LPS), and crocin was intraperitoneally administrated one week before the lesion, and then treatment continued for 21 days...
February 15, 2024: Heliyon
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