NHERF2 regulatory function in signal transduction pathways and control of gene expression: Implications for cellular homeostasis and breast cancer

Archives of Medical Research, Journal Year: 2025, Volume and Issue: 56(4), P. 103179 - 103179

Published: Jan. 14, 2025

Na⁺/H⁺ exchanger regulatory factor 2 (NHERF2) is a nucleocytoplasmic protein initially identified as regulator of membrane-bound sodium-hydrogen 3 (NHE3). In the cytoplasm, NHERF2 regulates activity G protein-coupled receptors (GPCRs), including beta-2 adrenergic receptor (2β-AR), lysophosphatidic acid 2, and parathyroid hormone type 1 receptor. nucleus, acts coregulator transcription factors such sex-determining region Y (SRY), involved in male sex determination, estrogen alpha (ERα). ERα ligand-dependent that controls mammary gland growth differentiation during puberty pregnancy plays major role development progression breast cancer tumors. Altogether, functions on ion channels, GPCRs, nuclear have modulatory effect signal transduction pathways, metabolic homeostasis, cell proliferation differentiation, neurotransmission, muscle contraction, renal electrolyte balance. This work highlights cytoplasm nucleus underscores mechanisms through which participates regulation gene expression tumor cancer.

Language: Английский

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Differential associations between cytokine and complement proteins in the clinical high risk and first episode stages of psychosis: Blood based investigation across three international studies of psychosis: NEURAPRO, STEP and OPTiMiSE

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

Published: Jan. 14, 2025

Dysregulation of inflammatory mediators and complement cascade proteins has been implicated in psychosis. In the current study, we aimed to investigate relationship between cytokines blood from people at clinical high risk (CHR) for psychosis first episode (FEP). Baseline samples two cohorts CHR participants [NEURAPRO (n = 153) STEP 146)], one cohort FEP patients [OPTiMiSE 226)] were included. The levels three Inflammatory markers including Interleukin (IL)-6, Tumour necrosis factor-alpha (TNF-α) C-reactive protein (CRP) along with about 30 considered analyses. First, evaluated interrelationship then using regression models, investigated their association proteins. We detected positive associations among all IL-6, TNF-α, CRP individuals, whereas was observed only IL-6 TNF-α. Regression models showed strong C3, C4A, C4B, C5, CFB CFI both cohorts. This indicates presence a related pro-inflammatory tone developing contrast, cohort, C1QA, FCN-2, MASP2 an inverse no found or CRP. These results suggest switch immune activity peripheral circulation compared CHR. novel findings propose that protein-targeted anti-inflammatory therapy could be effective state hence used early intervention

Language: Английский

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The Clinical and Laboratory Landscape of COVID-19 During the Initial Period of the Pandemic and at the Beginning of the Omicron Era

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 481 - 481

Published: March 27, 2025

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent significant mutations, resulting in the Omicron variant. Methods: In this study, we analyzed blood samples from 98 patients with disease 19 (COVID-19) hospitalized during initial SARS-CoV-2 wave and onset of 2021. High-resolution melting (HRM) analysis PCR products was used to analyze RNA extracted clinical collected July November 2021 infected SARS-CoV-2. Results: HRM revealed a characteristic deletion N protein virus isolated 2021, associated Elevated levels inflammatory markers interleukin-6 (IL-6) were observed both waves COVID-19. Complement IgG IgM antibodies detected more often second wave. An increase hemagglutinin-inhibiting (HI) against influenza viruses paired specimens moderate severe COVID-19 outbreaks. Conclusions: Patients admitted showed rise markers, suggesting that triggers responses. The rapid formation may indicate faster immune response. Seasonal flu negatively impact course infections.

Language: Английский

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Novel therapeutic receptor agonists and antagonists in allergic conjunctivitis

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 24(5), P. 380 - 389

Published: July 22, 2024

Allergic conjunctivitis is characterized by the development of pathophysiological changes to ocular surface, which occurs when pro-allergic and pro-inflammatory mediators interact with their cognate receptors expressed on immune nonimmune cells. Traditional treatments antihistamines corticosteroids provide relief, but there a need for more efficacious tolerable long-term therapy better safety profile. This article aims an overview mode action clinical application agonist therapies targeting glucocorticoid, melanocortin, toll-like receptors, as well antagonist cytokine, chemokine, integrin, histamine receptors.

Language: Английский

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Neutrophil extracellular traps as immunofibrotic mediators in RA-ILD; pilot evaluation of the nintedanib therapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 23, 2024

Objective Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a significant pulmonary complication of RA. This study tried to elucidate the mechanisms enhancing inflammation and causing injury in RA-ILD, focusing on role neutrophil extracellular traps (NETs). The also investigated potential benefits nintedanib advanced disease. Methods Nine RA-ILD patients nine healthy controls were included study. Inflammatory markers patients’ circulation evaluated with immunoassays. formation NETs was examined using citrullinated histone H3 (CitH3) ELISA cell immunofluorescence. proteins expressed neutrophils/NETs studied real-time qPCR NET ELISA. To assess effect nintedanib, an intracellular tyrosine kinase inhibitor antifibrotic properties, paired conducted five before treatment administration 16 weeks later. Results soluble terminal complement complex sC5b-9 levels CitH3 significantly elevated compared controls. In addition, neutrophils isolated from released enriched tissue factor interleukin-17A. had dynamic role, increasing fibrotic human fibroblasts (HPFs). On other hand, decreased patients. Conclusion findings propose interplay between circulating HPFs, establishing immunofibrotic aspects RA-ILD. They support effectiveness reducing key pathological processes Further research needed fully understand these optimize strategies for

Language: Английский

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Complement Immune System in Pulmonary Hypertension-Cooperating Roles of Circadian Rhythmicity in Complement-Mediated Vascular Pathology

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12823 - 12823

Published: Nov. 28, 2024

Originally discovered in the 1890s, complement system has traditionally been viewed as a "compliment" to body's innate and adaptive immune response. However, emerging data have shown that is much more complex mechanism within body involved regulating inflammation, gene transcription, attraction of macrophages, many processes. Sustained activation contributes autoimmunity chronic inflammation. Pulmonary hypertension disease with poor prognosis an average life expectancy 2-3 years leads vascular remodeling pulmonary arteries; arteries are essential host homeostasis, they divert deoxygenated blood from right ventricle heart lungs for gas exchange. This review focuses on direct links between system's involvement hypertension, along autoimmune conditions, reliance processes artery. Furthermore, circadian rhythmicity highlighted disrupted homeostatic inflammatory consequences arteries, which could potentially open new therapeutic cues. The current treatment options discussed clinical trials using inhibitors potential targets impact cell functions activation, alleviate symptoms block progression disease. Further research complement's interstitial lung diseases prove beneficial our understanding these various prevent arteries.

Language: Английский

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Role of Complement Components in Asthma: A Systematic Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(11), P. 3044 - 3044

Published: May 22, 2024

Background: Asthma is a chronic inflammatory airway disease characterized by recurrent symptoms in response to wide range of external stimuli, including allergens, viral infections, and air pollution together with internal host-derived danger signals. The traditionally associated adaptive immune responses; recent research emphasizes the critical role innate immunity its pathogenesis. complement system, activated as part defense mechanisms, plays crucial bridging immunity. While experimental models demonstrate cascade activation asthma, human studies remain limited. Methods: This systematic review summarizes existing literature on system asthma patients, gathering data from PubMed, Web Science, Scopus, Google Scholar. protocol was registered OSF. Results: Out 482 initially identified articles, only 24 met eligibility criteria, revealing disparities sample origin, methodologies, populations. Despite observed heterogeneity, consistent result found elevation regulatory proteins, such Factor H, samples patients compared those healthy subjects. Conclusions: increased level H I highlight that these may influence pathophysiology. factors potential biomarkers activity severity needs further evaluation.

Language: Английский

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Transcriptome-Wide Root Causal Inference

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

ABSTRACT Root causal genes correspond to the first gene expression levels perturbed during pathogenesis by genetic or non-genetic factors. Targeting root has potential alleviate disease entirely eliminating pathology near its onset. No existing algorithm discovers from observational data alone. We therefore propose Transcriptome-Wide Causal Inference (TWRCI) that identifies and their graph using a combination of variant unperturbed bulk RNA sequencing data. TWRCI uses novel competitive regression procedure annotate cis trans-genetic variants they directly cause. The simultaneously recovers ordering pinpoint underlying estimate effects. outperforms alternative approaches across diverse group metrics targeting while accounting for distal relations, linkage disequilibrium, patient heterogeneity widespread pleiotropy. demonstrate uncovering mechanisms two complex diseases, which we confirm replication independent genome-wide summary statistics.

Language: Английский

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A novel approach for breast cancer treatment: the multifaceted antitumor effects of rMeV-Hu191

Hereditas, Journal Year: 2024, Volume and Issue: 161(1)

Published: Sept. 28, 2024

Language: Английский

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