A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(9), P. 1690 - 1721

Published: Feb. 20, 2024

Abstract Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific components facilitating and their mechanisms of action remain largely unknown. Here, we show that a female gland-specific protein, here named A. aegypti Neutrophil Recruitment Protein ( Aa NRP), facilitates Zika dengue viruses. NRP promotes rapid influx neutrophils, followed by virus-susceptible myeloid cells toward bite sites, which establishment local infection systemic dissemination. Mechanistically, engages TLR1 TLR4 skin-resident macrophages activates MyD88-dependent NF-κB signaling induce expression neutrophil chemoattractants. Inhibition MyD88-NF-κB with dietary phytochemical resveratrol reduces NRP-mediated enhancement flavivirus mosquitoes. These findings exemplify how can aid transmission, suggest potential prophylactic target.

Language: Английский

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Network Pharmacology Analysis and Experimental Validation of Kaempferol in the Treatment of Ischemic Stroke by Inhibiting Apoptosis and Regulating Neuroinflammation Involving Neutrophils

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12694 - 12694

Published: Oct. 21, 2022

Kaempferol, a natural plant flavonoid compound, has neuroprotective effect on ischemic stroke, while the specific mechanism remains unclear. In current study, we applied comprehensive strategy that combines network pharmacology and experimental evaluation to explore potential of kaempferol in treatment cerebral ischemia. First, analysis identified biological process kaempferol, suggesting may partly help treating stroke by regulating apoptosis inflammatory response. Then, evaluated efficacy acute stage elucidated its effects possible mechanisms cell neuroinflammation involved neutrophils. The results showed could significantly reduce modified neurological severity score (mNSS), volume infarction degree edema. terms anti-apoptosis, number TUNEL-positive cells, inhibit expression pro-apoptotic proteins promote anti-apoptotic proteins. Kaempferol play an role up-regulating level BDNF-TrkB-PI3K/AKT signaling pathway. addition, found inhibited neuron loss activation glial as well protein COX-2 classic pro-inflammatory pathway TLR4/MyD88/NF-κB brain, reduced MPO activity neutrophil counts peripheral blood, down-regulated aggregation infiltration brain. Western blot revealed JAK1/STAT3 neutrophils brains. Our study rat blood which be related down-regulation

Language: Английский

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MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway

Respiratory Research, Journal Year: 2023, Volume and Issue: 24(1)

Published: Oct. 25, 2023

Abstract Background Neutrophilic airway inflammation is a challenge in asthma management and associated with poor patient prognosis. Mucin 1 (MUC1), which contains cytoplasmic tail (MUC1-CT), has been found to mediate glucocorticoid sensitivity asthma; however, its role modulating neutrophilic remains unknown. Methods Human-induced sputum cells were collected from healthy participants (n = 12), patients mild-to-moderate 34), those severe 18). In vitro human lung bronchial epithelial cell line (BEAS-2B) was transfected small interfering RNA against MUC1 (MUC1-siRNA) then stimulated by lipopolysaccharide (LPS), where some pretreated TLR4 inhibitor (TAK-242). vivo mouse model of asthmatic neutrophil induced ovalbumin (OVA)/LPS. Some groups intraperitoneally injected MUC1-CT (GO-203) and/or TAK-242 . Results The mRNA expression downregulated the correlated inflammation. expressions TLR4, MyD88, nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3), caspase-1, interleukin (IL)-18, IL-1β upregulated related MUC1. LPS activated pathway NLRP3-mediated pyroptosis BEAS-2B vitro, significantly aggravated after MUC1-siRNA transfection. Furthermore, MUCl-CT interacted interaction between MyD88 increased MUCl-siRNA Moreover, ameliorated TLR4/MyD88/nuclear factor kappa B (NF-κB) activation, NLRP3 inflammasome-mediated pyroptosis, exacerbated downregulation. GO-203 TLR4/MyD88/NF-κB activation vivo, reduced OVA/LPS; these pathological changes partially alleviated application. Conclusion This study revealed that downregulation plays an important reduces inhibiting pathway, thereby attenuating asthma.

Language: Английский

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Microglial TLR4/NLRP3 Inflammasome Signaling in Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 97(1), P. 75 - 88

Published: Dec. 1, 2023

Alzheimer’s disease is a pervasive neurodegenerative that estimated to represent approximately 70% of dementia cases worldwide, and the molecular complexity has been highlighted remains poorly understood. The accumulation extracellular amyloid-β (Aβ), intracellular neurofibrillary tangles formed by tau hyperphosphorylation, neuroinflammation are major pathological features (AD). Over years, there no apparent breakthrough in drug discovery based on Aβ hypotheses. Neuroinflammation gradually become hot spot AD treatment research. As primary cells innate immunity central nervous system, microglia play key role neuroinflammation. Toll-like receptor 4 (TLR4) nucleotide-binding oligomerization domain-like 3 (NLRP3) inflammasomes vital molecules In context AD, complex interplay between TLR4 NLRP3 influences pathology via this review, effect activation inhibition pathology, as well cross-talk inflammasome, influence essential relevant signaling pathway were expounded. addition, feasibility these factors representing potential option for clarified.

Language: Английский

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Echinatin alleviates inflammation and pyroptosis in hypoxic-ischemic brain damage by inhibiting TLR4/ NF-κB pathway

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 136, P. 112372 - 112372

Published: June 7, 2024

Language: Английский

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Effects of Dietary Macleaya cordata Extract Containing Isoquinoline Alkaloids Supplementation as an Alternative to Antibiotics in the Diets on Growth Performance and Liver Health of Broiler Chickens

Frontiers in Veterinary Science, Journal Year: 2022, Volume and Issue: 9

Published: July 27, 2022

This study aimed to investigate the effects of dietary supplementation with Macleaya cordata extract (MCE) containing protopine and allotypotopine on growth performance liver health in broiler chickens. A total 486 1-day-old male AA chickens were randomly assigned following three groups: (1) control (CON) group, fed a basal diet; (2) AGP group (positive control), diet supplemented 50 mg/kg aureomycin; (3) MCE 0.6 including 0.4 0.2 allotypotopine. The results showed that had significantly higher final body weight average daily gain from d 0 42 than other groups ( p < 0.05), both lower feed-to-gain ratio CON 0.05). Serum protein, high-density lipoprotein cholesterol, low-density glucose, immunoglobulin A, M, complements (C3, C4) concentrations Dietary or aureomycin reduced hepatic contents 8-hydroxy-2'-deoxyguanosine, malondialdehyde, interleukin (IL)-1β, IL-6, NLRs family pyrin domain 3 (NLRP3), caspase-1 Moreover, inhibited mRNA expressions Toll-like receptor 4, myeloid differentiation factor 88, nuclear factor-κB, NLRP3, as well expression Bax Bcl-2 Therefore, our suggested allocryptopine improved benefited possibly through inhibiting caspase-1-induced pyroptosis by inactivating TLR4/MyD88/NF-κB/NLRP3 signaling pathway, provided support for application an alternative antibiotics feed industry.

Language: Английский

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Role of pattern recognition receptors in the development of MASLD and potential therapeutic applications

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116724 - 116724

Published: May 17, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent diseases worldwide, and its occurrence is strongly associated with obesity, insulin resistance (IR), genetics, metabolic stress. Ranging from simple fatty to steatohepatitis (MASH), even severe complications such as fibrosis advanced cirrhosis or hepatocellular carcinoma, underlying mechanisms MASLD progression are complex involve multiple cellular mediators related signaling pathways. Pattern recognition receptors (PRRs) innate immune system, including Toll-like (TLRs), C-type lectin (CLRs), NOD-like (NLRs), RIG-like (RLRs), DNA receptors, have been demonstrated potentially contribute pathogenesis for MASLD. Their pathways can induce inflammation, mediate oxidative stress, affect gut microbiota balance, ultimately resulting in hepatic steatosis, inflammatory injury fibrosis. Here we review available literature regarding involvement PRR-associated signals pathogenic clinical features MASLD, vitro animal models We also discuss emerging targets PRRs drug developments that involved agent therapies intended arrest reverse progression, thus enabling refinement therapeutic accelerate development.

Language: Английский

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Sulfate-Reducing Bacteria Induce Pro-Inflammatory TNF-α and iNOS via PI3K/Akt Pathway in a TLR 2-Dependent Manner

Microorganisms, Journal Year: 2024, Volume and Issue: 12(9), P. 1833 - 1833

Published: Sept. 5, 2024

, resident gut sulfate-reducing bacteria (SRB), are found to overgrow in diseases such as inflammatory bowel disease and Parkinson's disease. They activate a pro-inflammatory response, suggesting that

Language: Английский

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What type of cell death occurs in chronic cerebral hypoperfusion? A review focusing on pyroptosis and its potential therapeutic implications

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 2, 2023

Chronic cerebral hypoperfusion (CCH) is a major global disease with chronic blood flow reduction. It also the main cause of cognitive impairment and neurodegenerative diseases. Pyroptosis, novel form cell death, characterized by rupture membrane release pro-inflammatory mediators. In recent years, an increasing number studies have identified involvement pyroptosis its mediated inflammatory response in pathological process CCH. Therefore, preventing activation following CCH beneficial to inhibit cascade reduce brain injury. this review, we discuss research progress on relationship between CCH, order provide reference for related fields.

Language: Английский

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Advanced development and mechanism of sepsis-related acute respiratory distress syndrome

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 14, 2022

The introduction of the Sepsis 3.0 guidelines in 2016 improved our understanding sepsis diagnosis and therapy. Personalized treatment strategies nursing methods for patients are recommended “Save Campaign” 2021. However, mortality remains high. Patients with sepsis-related acute respiratory distress syndrome account around 30% them, fatality rates ranging from 30 to 40%. Pathological specimens individuals ARDS frequently demonstrate widespread alveolar damage, investigations have revealed that pulmonary epithelial endothelial injury is underlying cause. As a result, purpose this work evaluate mechanism research progress damage ARDS, which may provide new directions future research, diagnosis,

Language: Английский

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