BACKGROUNDOtitis media with effusion (OME) often leads to pediatric hearing loss and is influenced by innate and adaptive immune responses. Innate immunity serves as the non-specific first line of defense against OME.METHODSWe induced OME in rats using ovalbumin. We administered IL-6 monoclonal antibodies intranasally to inhibit IL-6, and we injected an NF-κB inhibitor intraperitoneally to explore the role of IL-6 in innate immunity and its interaction with the NOD-like receptor signaling pathway. We analyzed RNA-sequencing data with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways to assess signaling pathways involved in OME. We also utilized Western blot, quantitative real-time PCR, and immunohistochemistry on middle ear samples and used microscopy to identify immune cells in ear wash fluids.RESULTSOur study suggests a pivotal role for IL-6 in the immune pathways of rats with OME via the regulation of CXCL1-mediated pathways. Increased levels of IL-6 and CXCL1 were observed in the middle ear tissues, and activation of the NLRP3 inflammasome in OME rats led to an immune response via NF-κB, thus promoting IL-6 and CXCL1 production, which was reduced by IL-6 antibody treatment.CONCLUSIONSOur findings confirm that IL-6 and CXCL1 play significant roles in the innate immune response in OME in rodents, predominantly via the NOD-like receptor signaling pathway and NLRP3 inflammasome activation. This research sheds light on OME pathogenesis and its immune-related mechanisms.

2024-12-01·Current Drug Targets

Therapeutic Correlation of TLR-4 Mediated NF-κB Inflammatory Pathways in Ischemic Injuries

Article

作者: Sharma, Prateek ; Sharma, Veerta ; Singh, Thakur Gurjeet

:Ischemia-reperfusion (I/R) injury refers to the tissue damage that happens when blood flow returns to tissue after a period of ischemia. I/R injuries are implicated in a large array of pathological conditions, such as cerebral, myocardial, renal, intestinal, retinal and hepatic ischemia. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as significant contributors to inflammation caused by pathogens and, more recently, inflammation caused by injury. TLR-4 activation initiates a series of events that results in activation of nuclear factor kappa-B (NF-κB), which stimulates the production of pro-inflammatory cytokines and chemokines, exacerbating tissue injury. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the TLRs signalling pathway and the role of TLR-4/NF-κB in the pathophysiology of I/R injuries. Furthermore, this review highlights the various pharmacological agents (TLR-4/NF-κB inhibitors) with special emphasis on the various ischemic injuries (cerebral, myocardial, renal, intestinal, retinal and hepatic). Future research should prioritise investigating the specific molecular pathways that cause TLR-4/NF-κBmediated inflammation in ischemic injuries. Additionally, efforts should be made to enhance treatment approaches in order to enhance patient outcomes.

2024-12-01·Molecular Biology Reports

The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges

Review

作者: Deng, Song ; Sun, Jun ; Yuan, Ping

The nuclear factor-κB (NF-κB) family, consisting of several transcription factors, has been implicated in the regulation of cell proliferation and invasion, as well as inflammatory reactions and tumor development. Cervical cancer (CC) results from long-term interactions of multiple factors, among which persistent high-risk human papillomavirus (hrHPV) infection is necessary. During different stages from early to late after HPV infection, the activity of NF-κB varies and plays various roles in carcinogenesis and progress of CC. As the center of the cell signaling transduction network, NF-κB can be activated through classical and non-classical pathways, and regulate the expression of downstream target genes involved in regulating the tumor microenvironment and acquiring hallmark traits of CC cells. Targeting NF-κB may help treat CC and overcome the resistance to radiation and chemotherapy. Even though NF-κB inhibitors have not been applied in clinical treatment as yet, due to limitations such as dose-restrictive toxicity and poor tumor-specificity, it is still considered to have significant therapeutic potential and application prospects. In this review, we focus on the role of NF-κB in the process of CC occurrence and hallmark capabilities acquisition. Finally, we summarize relevant NF-κB-targeted treatments, providing ideas for the prevention and treatment of CC.

项与 NF-κB inhibitors(China Pharmaceutical University) 相关的新闻（医药）

2024-04-18

·GlobeNewswire-Health Care

BioVie to Present Data Showing How NE3107 Potentially Restores Homeostasis via Specific Genes Associated with Dementia, Metabolism, and Inflammation

Additionally, the Company announced approval of the non-proprietary name “bezisterim” for NE3107CARSON CITY, Nev., April 18, 2024 (GLOBE NEWSWIRE) -- BioVie Inc. (Nasdaq: BIVI), (“BioVie” or the “Company”), a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease, today announced that an oral presentation and poster presentation will be shared at the 12th Annual Alzheimer's & Parkinson's Drug Development Summit to be held in Boston, Massachusetts April 23-25. Additionally, the United States Adopted Names (USAN) Council, and the World Health Organization (WHO) International Nonproprietary Names (INN) expert committee has approved “bezisterim” as the non-proprietary (generic) name for NE3107, an orally active partial NF-κB inhibitor product candidate being studied in Parkinson’s Disease and Alzheimer’s Disease. The oral and poster presentations 12th Annual Alzheimer's & Parkinson's Drug Development Summit will provide additional details on how bezisterim appears to have an impact on DNA methylation on 5 different “clocks” measuring biological age and that the extent of DNA methylation is correlated to a series of clinical measures. The oral presentation titled “Clinical Outcomes and Biomarker Findings from a Randomized, Placebo-Controlled Trial of NE3107 in Subjects with Mild to Moderate Probably Alzheimer’s Disease” will be presented by Christopher L. Reading, BioVie’s Senior Vice President, Alzheimer’s Disease Program, on Wednesday, April 24 at 2:30 p.m. EDT. The poster with the same title will be presented at 6:45 p.m. on the same day. Details of the presented data and conclusions will be announced once the presentations are made public at the conference. About BioVie Inc.BioVie Inc. (NASDAQ: BIVI) is a clinical-stage company developing innovative drug therapies for the treatment of neurological and neurodegenerative disorders and advanced liver disease. In neurodegenerative disease, the Company’s drug candidate bezisterim inhibits inflammatory activation of ERK and NFkB (e.g., TNF signaling) that leads to neuroinflammation and insulin resistance, but not their homeostatic functions (e.g., insulin signaling and neuron growth and survival). Both are drivers of Alzheimer’s and Parkinson’s diseases. The Company conducted and reported efficacy data on its randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate bezisterim in patients who have mild to moderate Alzheimer's disease (NCT04669028). Results of a Phase 2 investigator-initiated trial (NCT05227820) showing bezisterim-treated patients experienced improved cognition and biomarker levels were presented at the Clinical Trial in Alzheimer’s Disease annual conference in December 2022. An estimated six million Americans suffer from Alzheimer’s. A Phase 2 study of bezisterim in Parkinson’s disease (NCT05083260) has completed, and data presented at the International Conference on Alzheimer's and Parkinson's Disease and Related Neurological Disorders conference in Gothenburg, Sweden in March 2023 showed significant improvements in “morning on” symptoms and clinically meaningful improvement in motor control in patients treated with a combination of bezisterim and levodopa vs. patients treated with levodopa alone, and no drug-related adverse events. In liver disease, the Company’s Orphan drug candidate BIV201 (continuous infusion terlipressin), with U.S Food and Drug Administration (“FDA”) Fast Track status, is being evaluated and discussed with guidance received from the FDA regarding the design of Phase 3 clinical testing of BIV201 for the treatment of ascites due to chronic liver cirrhosis. The active agent is approved in the U.S. and in about 40 countries for related complications of advanced liver cirrhosis. For more information, visit http://www.bioviepharma.com/. Forward-Looking StatementsThis press release contains forward-looking statements, which may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. Although BioVie Inc. believes such forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. Actual results may vary materially from those expressed or implied by the statements herein due to the Company's ability to successfully raise sufficient capital on reasonable terms or at all, available cash on hand and contractual and statutory limitations that could impair our ability to pay future dividends, our ability to complete our pre-clinical or clinical studies and to obtain approval for our product candidates, our ability to successfully defend potential future litigation, changes in local or national economic conditions as well as various additional risks, many of which are now unknown and generally out of the Company's control, and which are detailed from time to time in reports filed by the Company with the SEC, including quarterly reports on Form 10-Q, reports on Form 8-K and annual reports on Form 10-K. BioVie Inc. does not undertake any duty to update any statements contained herein (including any forward-looking statements), except as required by law. For Investor Relations Inquiries:Bruce MackleManaging Director, LifeSci Advisors, LLCbmackle@lifesciadvisors.com For Media Relations Inquiries:Melyssa WeibleManaging Partner, Elixir Health Public Relationsmweible@elixirhealthpr.com

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100 项与 NF-κB inhibitors(China Pharmaceutical University) 相关的药物交易

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