Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1462 - 1462

Published: Nov. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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Suppression of CYLD by HER3 confers ovarian cancer platinum resistance via inhibiting apoptosis and by inducing drug efflux

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Feb. 26, 2025

Abstract Background Ovarian cancer (OC) is the most pathogenic gynecological malignant tumor in world. Due to difficulty of early diagnosis, patients developed chemo-resistance and recurrence during/after chemotherapy. Methods CCK8 flow cytometry were utilized assess drug sensitivity apoptosis parental resistant cell lines. CYLD knockdown or overexpressed cells employed investigate its regulatory involvement DDP resistance. Clinical samples have been clinical relevance CYLD. The synergistic effects investigated through combination methods a nude mice model with ABCB1 inhibitor HER3 inhibitor. Results In this study, we found that levels significantly reduced DDP-resistant tissues compared normal cells. DDP-sensitive was sufficient converse become by reducing increasing Bcl-XL inhibiting Bax, efflux via upregulating expression. expression substantially higher cells, upstream facilitator suppressing STAT3 signaling. Furthermore, overexpression increased platinum-based chemotherapy both vitro vivo. key downstream target for regulating growth therapeutic resistance vivo, promoted translocation p65 nucleus which transcriptional activation. High rendered suppression, consequently, mediated blocking pathways promoting ovarian cancer. Conclusions Our findings identify novel HER3/CYLD/ABCB1 axis regulate resistance, may be used as potential target(s) overcome

Language: Английский

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Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8621 - 8621

Published: Aug. 7, 2024

Inflammation is activated by diverse triggers that induce the expression of cytokines and adhesion molecules, which permit a succession molecules cells to deliver stimuli functions help immune system clear primary cause tissue damage, whether this an infection, tumor, or trauma. During inflammation, short-term changes in secretion strong mediators inflammation occur, while long-term occur specific groups cells. Long-term include cellular transdifferentiation for some types need regenerate damaged tissue, as well death can be detrimental integrity if they remain active beyond boundaries essential function. The transcriptional regulator NFκB enables fundamental gene during development. recurrence malignant disease, cell stress-induced alterations enable growth cancer clones are substantially resistant therapeutic intervention system. A number those due significant defects feedback signal cascades control activity NFκB. Specifically, stress contributes it overrides modules otherwise protect host tissue. involved both suppression promotion cancer, key distinctive feature determines its net effect remains unclear. This paper aims provide answer at least one aspect question, namely mechanism divergent response critical inflammatory general.

Language: Английский

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LMAN2 interacts with HEATR3 to expedite HER2-positive breast cancer advancement and inflammation and Akt/ERK/NF-κB signaling

Biochemistry and Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

The paper aimed to reveal the impacts and possible mechanism of action lectin mannose-binding 2 protein (LMAN2) in HER2-positive breast cancer (BC). expression, prognostic potential LMAN2, correlation between LMAN2 HEAT repeat containing 3 (HEATR3) BC were analyzed TCGA database. Intact, Mentha, BioGrid databases predicted LMAN2–HEATR3 interactions. Reverse transcription-quantitative PCR Western blot examined expression. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine staining, wound healing, transwell assays, respectively, detected aggressive cellular biological behaviors including proliferation, migration, invasion. expression matrix metalloproteinases, HEATR3, kinase B (Akt)/extracellular signal-regulated (ERK)/nuclear factor-kappaB (NF-κB) signaling-related proteins. Co-immunoprecipitation assay was used prove relationship with HEATR3. Enzyme-linked immunosorbent inflammatory cytokine levels. overexpressed tissues cells indicated unfavorable prognosis patients. knockdown suppressed cell interacted had a positive HEATR3 up-regulation reversed repressive role interference progression BC, Akt/ERK/NF-κB signaling, response. Altogether, silencing might exert anti-tumor anti-inflammatory properties inactivate signaling via binding

Language: Английский

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Golden berry fruit modulates inflammation in LPS-stimulated RAW 264.7 macrophages and the DSS-induced acute colitis model

Journal of Functional Foods, Journal Year: 2025, Volume and Issue: 125, P. 106665 - 106665

Published: Jan. 8, 2025

Language: Английский

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Supplementation with N-Acetyl-L-cysteine during in vitro maturation improves goat oocyte developmental competence by regulating oxidative stress.

Theriogenology, Journal Year: 2025, Volume and Issue: 235, P. 221 - 230

Published: Jan. 17, 2025

Language: Английский

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Network Pharmacology and Experimental Verification: Phellodendri Chinensis Cortex-Cnidii Fructus Herb Pair Alleviates Atopic Dermatitis by Regulating the TLR4/NF-κB Pathway

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1451 - 1474

Published: Feb. 1, 2025

Atopic Dermatitis (AD) is a common continuous inflammation dermatosis requiring efficacious therapeutic intervention. Phellodendri Chinensis Cortex-Cnidii Fructus (PC) herb pair has shown effectiveness and security in traditional Chinese medicine (TCM) clinical applications, yet its pharmacological constituents mechanisms are not fully elucidated. This study used serum pharmacochemistry, network pharmacology, validation experiments to examine the impact of PC treatment AD. Initially, ultra performance liquid chromatography-mass spectrometry (UPLC-MS) had been applied elucidate components that were absorbed. An integrative approach combining pharmacology vivo research (general index observation, skin pathological tissue staining, ELISA, immunohistochemistry, immunofluorescence, Western blotting) was employed validate PC's mechanism action after 2,4-dinitrochlorobenzene (DNCB) create mouse model Fifty-three compounds 18 prototype characterized within PC. The efficacy AD notably manifested alleviation pruritus, improvement histopathology, reduction cytokines involving IgE, IL-4, TNF-α IL-6. Based on molecular docking studies, pharmacodynamic such as phellodendrine, xanthotoxin, nomilin, isopimpinellin strongly favored main targets. Comprehensive investigations integrating studies revealed prevented DNCB-induced through adjusting TLR4/NF-κB signaling pathway. anti-AD effects may be attributed modulation pathway, NF-кB expression nucleusim, downregulation inflammatory cytokine levels, provement histopathological manifestations, pruritus.

Language: Английский

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Inflammatory Biomarkers and Oral Health Disorders as Predictors of Head and Neck Cancer: A Retrospective Longitudinal Study

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2279 - 2279

Published: March 4, 2025

Head and neck cancers (HNCs) are often diagnosed late, leading to poor prognosis. Chronic inflammation, particularly periodontitis, has been linked carcinogenesis, but systemic inflammatory markers remain underexplored. This study was the first examine whether elevated C-reactive protein (CRP) can serve as a cost-effective adjunct in HNC risk assessment, alongside oral health indicators. A retrospective cohort analysed 23,742 hospital records (4833 patients, 2015-2022) from University Hospital of Debrecen. cases were identified using ICD-10 codes, with CRP periodontitis key predictors. Kaplan-Meier survival analysis, log-rank tests, Weibull regression used assess risk, model performance evaluated via AIC/BIC ROC curves. Periodontitis significantly associated (HR 5.99 [1.96-18.30]), while (>15 mg/L) independently increased 4.16 [1.45-12.00]). Females had lower than males 0.06 [0.01-0.50]). may cost-effective, easily accessible biomarker for early detection when combined screening. Integrating inflammation into assessment models could potentially improve diagnosis high-risk populations.

Language: Английский

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The Tumor-Promoting Role of Neutrophil Extracellular Traps in Esophageal Squamous Cell Carcinoma and Their Interaction with the Gut Microbiota

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Background and Objectives In recent years, the role of neutrophil extracellular traps (NETs) in tumor microenvironment has garnered increasing attention, yet their relationship with esophageal squamous cell carcinoma (ESCC) remains poorly understood. Additionally, interplay between gut microbiota immune may influence progression ESCC. This study aims to investigate diagnostic value NETs-related markers (CitH3, MPO, NE) ESCC patients, correlation clinical characteristics, impact NETs levels on patient prognosis. Furthermore, we seek elucidate pro-tumorigenic mechanisms By analyzing composition, also aim uncover differences microbial communities patients healthy individuals explore association levels, thereby providing novel theoretical foundations for early diagnosis treatment Methods Peripheral blood, surgical specimens, fecal samples, data were collected from 60 undergoing treatment, along peripheral blood samples controls. ELISA was employed measure plasma CitH3, NE both groups, correlations features analyzed. The efficacy evaluated using ROC curves, 3-year survival rates high versus low CitH3 compared. Changes pre- post-surgery, as well different approaches NETs, assessed. 16S rDNA gene sequencing utilized analyze its explored. Immunohistochemistry, Western blot (WB), qRT-PCR performed detect expression specimens. In vitro experiments involved stimulating neutrophils phorbol esters generate followed by functional assays pathway analyses evaluate effects cells. A subcutaneous xenograft model nude mice established validate NETs. Results The significantly elevated compared those controls correlated characteristics. AUC diagnosing 0.981, demonstrating sensitivity specificity. Elevated indicative lower rates. Postoperative increased, robot-assisted minimally invasive esophagectomy (RAMIE) showing these video-assisted (VAMIE). Dysbiosis associated levels. revealed that promoted proliferation, migration, invasion, angiogenesis. WB analysis indicated facilitated epithelial-mesenchymal transition (EMT) angiogenesis upregulating protein N-Cadherin, Vimentin, MMP2, MMP9, HIF-1α, TNF-α, VEGF, VEGFA, Ang-1, Ang-2. vivo confirmed growth, DNase1 partially reversed this effect. Conclusions This elucidates tumor-promoting microbiota. offering prognostic value. promote regulating EMT pathways, reversing is linked These findings provide insights into targeted therapy ESCC, warranting further exploration regulatory

Language: Английский

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