Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes DOI Creative Commons
Yuan Zhou, Shu Zhang,

Jianning Zhang

et al.

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(1), P. 141 - 141

Published: May 6, 2022

Neuroinflammation and the NACHT, LRR, PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as new therapeutic strategy for many neuroinflammatory diseases. We studied effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to controlled cortical impact device. Maraviroc or vehicle injected intraperitoneally 1 hour after TBI then once per day consecutive days. Western blot, immunohistochemistry, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed evaluate molecular mechanisms at days post-TBI. Our results suggest that administration reduced activation, modulated microglial polarization from M1 M2, decreased neutrophil macrophage infiltration, inhibited release inflammatory factors TBI. Moreover, treatment activation neurotoxic reactive astrocytes, which, turn, exacerbated neuronal cell death. Additionally, we confirmed neuroprotective using modified neurological severity score, rotarod test, Morris water maze lesion volume measurements. In summary, our findings indicate might be desirable pharmacotherapeutic TBI, promising target improve recovery

Language: Английский

Pyroptosis: mechanisms and diseases DOI Creative Commons

Pian Yu,

Xu Zhang, Nian Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: March 29, 2021

Abstract Currently, pyroptosis has received more and attention because of its association with innate immunity disease. The research scope expanded the discovery gasdermin family. A great deal evidence shows that can affect development tumors. relationship between tumors is diverse in different tissues genetic backgrounds. In this review, we provide basic knowledge pyroptosis, explain tumors, focus on significance tumor treatment. addition, further summarize possibility as a potential treatment strategy describe side effects radiotherapy chemotherapy caused by pyroptosis. brief, double-edged sword for rational use dual effect will help us explore formation ideas patients to develop new drugs based

Language: Английский

Citations

1548
Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies DOI Open Access
Suowen Xu, Iqra Ilyas, Peter J. Little

et al.

Pharmacological Reviews, Journal Year: 2021, Volume and Issue: 73(3), P. 924 - 967

Published: June 4, 2021

The endothelium, a cellular monolayer lining the blood vessel wall, plays critical role in maintaining multiorgan health and homeostasis. Endothelial functions include dynamic maintenance of vascular tone, angiogenesis, hemostasis, provision an antioxidant, anti-inflammatory, antithrombotic interface. Dysfunction endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion hyperpermeability, endothelial cell senescence. Recent studies have implicated altered metabolism endothelial-to-mesenchymal transition as new features dysfunction. dysfunction is regarded hallmark many diverse human panvascular diseases, including atherosclerosis, hypertension, diabetes. has also been severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors interleukin 1β monoclonal antibodies, counter part their clinical benefits. regulation by noncoding RNAs provided novel insights into these newly described regulators dysfunction, thus yielding potential therapeutic approaches. Altogether, better understanding versatile (dys)functions cells will not only deepen our comprehension diseases but accelerate effective drug discovery. In this review, we provide timely overview multiple layers function, describe consequences mechanisms identify pathways targeted therapies.

Significance Statement

was initially considered be semipermeable biomechanical barrier gatekeeper health. recent decades, deepened biological led its recognition ubiquitous tissue regulating behavior, innate immunity, cell-cell interactions, wall. cardiovascular, metabolic, emerging infectious diseases. Pharmacotherapies targeting for treatment cardiovascular other

Language: Английский

Citations

688
Channelling inflammation: gasdermins in physiology and disease DOI Open Access
Xing Liu, Shiyu Xia, Zhibin Zhang

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(5), P. 384 - 405

Published: March 10, 2021

Language: Английский

Citations

546
Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment DOI Creative Commons

Sheng‐Kai Hsu,

Chia‐Yang Li, I‐Ling Lin

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 11(18), P. 8813 - 8835

Published: Jan. 1, 2021

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed death, such as ferroptosis, necroptosis, pyroptosis, recently been reported to play significant roles in the modulation cancer progression are considered a promising strategy for treatment. Thus, switch between pyroptosis also discussed. Cancer immunotherapy gained increasing attention due breakthroughs immune checkpoint inhibitors; moreover, highly correlated with immunity tumor microenvironment. Compared necroptosis primary mechanism host defense crucial bridging innate adaptive immunity. Furthermore, exerts benefits on immunotherapies, including inhibitors (ICIs) chimeric antigen receptor T-cell therapy (CAR-T). Hence, this review, we elucidate role We summarize potential small molecules nanomaterials target pyroptotic death mechanisms their therapeutic effects cancer.

Language: Английский

Citations

315
Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19? DOI Creative Commons
Jan Andersson, William Ottestad, Kevin J. Tracey

et al.

Molecular Medicine, Journal Year: 2020, Volume and Issue: 26(1)

Published: May 7, 2020

Abstract Background The 2019 novel coronavirus disease (COVID-19) causes for unresolved reasons acute respiratory distress syndrome in vulnerable individuals. There is a need to identify key pathogenic molecules COVID-19-associated inflammation attainable target with existing therapeutic compounds. endogenous damage-associated molecular pattern (DAMP) molecule HMGB1 initiates via two separate pathways. Disulfide-HMGB1 triggers TLR4 receptors generating pro-inflammatory cytokine release. Extracellular HMGB1, released from dying cells or secreted by activated innate immunity cells, forms complexes extracellular DNA, RNA and other DAMP pathogen-associated after lytic cell death. These are endocytosed RAGE, constitutively expressed at high levels the lungs only, transported endolysosomal system, which disrupted concentrations. Danger thus get access cytosolic proinflammatory instigating inflammasome activation. It conceivable that SARS-CoV-2 may reach cellular cytosol HMGB1-assisted transfer combined lysosome leakage. generally exists vivo bound molecules, including PAMPs DAMPs . plausible these specifically removed revealed 40% reduction of plasma arterial versus venous blood. Abundant pulmonary RAGE expression enables endocytosis danger be destroyed lysosomes physiological levels, but causing detrimental activation levels. Stress induces apoptosis endothelial females necrosis males. Conclusion Based on observations we propose considered as COVID-19.

Language: Английский

Citations

215
Cucurbitacin B inhibits non-small cell lung cancer in vivo and in vitro by triggering TLR4/NLRP3/GSDMD-dependent pyroptosis DOI Creative Commons
Renyikun Yuan,

Wentong Zhao,

Qinqin Wang

et al.

Pharmacological Research, Journal Year: 2021, Volume and Issue: 170, P. 105748 - 105748

Published: July 1, 2021

Pyroptosis, a type of programmed cell death (PCD), is characterized by swelling with bubbles, and the release inflammatory cytokines. Cucurbitacin B (CuB), extracted from muskmelon pedicel, natural bioactive product that could effectively exert anti-tumor activities in lung cancer. However, exact molecular mechanisms direct targets CuB non-small cancer (NSCLC) remain to be discovered. Here, we firstly found exerted an effect via pyroptosis NSCLC cells mice models. Next, based on docking cellular thermal shift assay (CETSA), identified directly bound Toll-like receptor 4 (TLR4) activate NLRP3 inflammasome, which further caused separation N- C-terminals Gasdermin D (GSDMD) execute pyroptosis. Moreover, enhanced mitochondrial reactive oxygen species (ROS), membrane protein Tom20 accumulation, cytosolic calcium (Ca

Language: Английский

Citations

189
NLRP3 inflammasome as a key driver of vascular disease DOI Open Access
Masafumi Takahashi

Cardiovascular Research, Journal Year: 2021, Volume and Issue: 118(2), P. 372 - 385

Published: Jan. 16, 2021

Abstract Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular innate immune that recognizes a diverse range of stimuli derived from pathogens, damaged or dead cells, and irritants. NLRP3 activation causes the assembly large multiprotein complex termed inflammasome, leads to secretion bioactive interleukin (IL)-1β IL-18 as well induction inflammatory cell death pyroptosis. Accumulating evidence indicates inflammasome plays key role in pathogenesis sterile diseases, including atherosclerosis other vascular diseases. Indeed, results Canakinumab Anti-inflammatory Thrombosis Outcome Study trial demonstrated IL-1β-mediated inflammation important atherothrombotic events suggested driver atherosclerosis. In this review, we will summarize current state knowledge regarding particular atherosclerosis, injury, aortic aneurysm, Kawasaki disease vasculitis, discuss therapeutic target for these disorders.

Language: Английский

Citations

128
Pyroptosis-induced inflammation and tissue damage DOI Creative Commons
Swathy O. Vasudevan, Bharat Behl, Vijay Rathinam

et al.

Seminars in Immunology, Journal Year: 2023, Volume and Issue: 69, P. 101781 - 101781

Published: June 21, 2023

Language: Английский

Citations

107
Organellar homeostasis and innate immune sensing DOI
Cassandra R. Harapas, Elina Idiiatullina, Mahmoud Al‐Azab

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(9), P. 535 - 549

Published: Feb. 23, 2022

Language: Английский

Citations

96
Melatonin attenuates LPS-induced pyroptosis in acute lung injury by inhibiting NLRP3-GSDMD pathway via activating Nrf2/HO-1 signaling axis DOI
Jia‐Ying Kang, Mengmeng Xu, Ying Sun

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 109, P. 108782 - 108782

Published: April 23, 2022

Language: Английский

Citations

84