Physiological functions of RIG-I-like receptors

Immunity, Год журнала: 2024, Номер 57(4), С. 731 - 751

Опубликована: Апрель 1, 2024

Язык: Английский

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CAR memory–like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer

Science Advances, Год журнала: 2024, Номер 10(28)

Опубликована: Июль 12, 2024

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory–like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In current study, CIML NK demonstrated superior antitumor responses against a panel EOC cell lines, increased expression activation receptors, up-regulation genes involved cycle/proliferation down-regulation inhibitory/suppressive genes. transduced with chimeric antigen receptor (CAR) targeting membrane-proximal domain mesothelin (MSLN) further improved MSLN-expressing patient-derived xenograft tumor cells. CAR arming subtanstially reduced their dysfunction ascites fluid transcriptomic changes related to altered metabolism tonic signaling as potential mechanisms. Lastly, adoptive transfer MSLN-CAR remarkable inhibition growth prevented metastatic spread mice, supporting an effective therapeutic strategy EOC.

Язык: Английский

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Enhancement of adipose stem cell quality via Cu‐MON: Transcriptome and bioinformatics analysis of normal and diabetic stem cells

FASEB BioAdvances, Год журнала: 2025, Номер unknown

Опубликована: Янв. 18, 2025

Abstract Transplanted adipose stem cells (ASC) have a low survival rate in the body, and there are not many ASC that can be effectively used, which weakens their tissue repair function. Based on this status quo, new type of copper‐based metal–organic network (Cu‐MON) was used to pretreat regulate cell activity order improve efficacy therapy or reduce number thus reducing cost clinical treatment. Gene expression changes before after Cu‐MON treatment normal donor (ND‐ASC) 2 diabetes mellitus (T2DM‐ASC) were evaluated through RNA sequencing, KEGG GO enrichment analysis. The results showed improved quality by regulating immune response promoting paracrine secretion. IL‐17 signaling pathway IL‐6, CXCL8, MMP‐9 key pathways necessary genes affected ability cells. In addition, also antiviral Type I interferon pathway. Our research had response, secretion, improving capabilities. This approach biomaterial pretreatment is fast, convenient, relatively safe, provides strategies for efficiency therapies.

Язык: Английский

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Single-Cell Sequencing of Peripheral Blood Mononuclear Cells Reveals Immune Landscape of Monkeypox Patients with HIV

Emerging Microbes & Infections, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

The monkeypox (MPXV) outbreak in 2022 is more prevalent among individuals with human immunodeficiency virus (HIV). While it plausible that HIV-induced immunosuppression could result a severe progression, the exact mechanisms remain undetermined. To better understand immunopathology of MPXV patients and without HIV infection, we employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from 6 hospitalized for MPXV, 3 whom had infection (HIV antibody positive & level below detection limit), only infected (HIV-). We map immune response both acute phase recovery period, showing reconfiguration cell phenotypes stage compared patients, characterized by disturbed subsets intense interactions mediated monocytes neutrophils. Importantly, besides different Mono/DC dynamic between + HIV- showed decreased NK expansion some CD8 T subsets, also found obviously dysregulated gene expression B cells, thus proposing mechanism underlying serious condition patients. In conclusion, our findings provide comprehensive atlas shed light on disease progression longer time individuals.

Язык: Английский

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Prognostic value of IFI27 in HNSCC and functional analysis under ALKBH5 regulation

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 24, 2025

This study aimed to investigate the expression levels and clinical implications of interferon α inducible protein 27 (IFI27) N6-methyladenosine (m6A) regulator Alkylation repair homolog 5 (ALKBH5) in head neck squamous cell carcinoma (HNSCC). We employed bioinformatics methods analyze differential IFI27 HNSCC its prognostic implications. Additionally, we explored pathways mechanisms associated with enrichment. Immunohistochemistry (IHC) was used detect adjacent normal tissues. significantly up-regulated (P < 0.001), correlated T stage tumor differentiation degree. The survival curve indicated that patients high had shorter overall compared those low expression. Furthermore, multivariate analysis confirmed is an independent factor patients. involved regulation type I III interferon-mediated responses, Retinoic acid-inducible gene (RIG-I) -like receptor signaling pathways, biological processes related innate immune responses. High a potential risk for onset progression HNSCC. down-regulation ALKBH5 may enhance via RIG-I/IFN-α axis, further influencing development

Язык: Английский

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A Four-Gene Signature from Blood to Exclude Bacterial Etiology of Lower Respiratory Tract Infection in Adults

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Unnecessary antibiotic use is a major driver of antimicrobial resistance, an urgent public health threat. There unmet need for improved diagnostics identifying bacterial etiology in acute respiratory infection (ARI). Hospitalized adults with ARI underwent comprehensive microbiologic testing and those definitive viral (n = 280), 129), or mixed viral-bacterial 95) had whole blood RNA sequencing. A hard-thresholded, mostly relaxed, LASSO-constrained logistic regression model was used to select parsimonious gene set ( ITGB4, ITGA7, IFI27, FAM20A ) highly capable discriminating any from nonbacterial (cross validated AUC 0.90). The 4-gene signature two independent cohorts (AUC 0.90-0.94). Thresholding the risk score yield 90% sensitivity detect resulted 71% specificity 91% negative predictive value. This defining absence may supplement clinical judgement management antibiotics ARI.

Язык: Английский

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Woodsmoke and Diesel Exhaust: Distinct Transcriptomic Profiles in the Human Airway Epithelium

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

ABSTRACT Climate change is increasing the frequency and severity of wildfires globally, causing significant woodsmoke (WS) emissions. Vehicles emit sizable amounts toxic traffic-related air pollution (TRAP), for which diesel exhaust (DE) a model. Both WS DE contain particulate matter <2.5 microns (PM 2.5 ) deeply penetrates lungs, respiratory epithelial inflammation that drives health effects. Regulations focus on PM concentration, despite emerging research highlights how composition mediates As are compositionally distinct, we conducted first head-to-head comparison effects transcriptomes air-liquid interface cultured primary human bronchial cells (HBEC). Differentiated donor-matched HBEC transwells were exposed 2-hours to filtered (FA; control), or (furnace tube burning pine) (Hatz 1B30E generator) both diluted 300 µg/m 3 . had higher ultrafine PM, whereas exposure contained significantly NO 2 , CO, O RNA sequencing showed resulted in 119 (↑41, ↓78) differentially expressed genes, while modulated 399 (↑255, ↓144) compared FA exposure. was associated with small ribosomal subunit cytochrome complex related HIF-1 signaling, chain interferon alpha/beta signaling/ISG15-protein conjugation, suggesting TRAP may enhance infection risk. We also analyzed protein immune-mediators. demonstrate two major sources modulate different genes pathways HBECs, minimal overlap. This informs debate regarding regulatory concentration assumptions similar concentrations have indistinct Highlights Lung wood smoke underexplored RNAseq WS-exposed lung revealed larger greater repression host antiviral response-associated than A miss composition-specific

Язык: Английский

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Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Апрель 10, 2025

Abstract Background Mycoplasma bovis is a prominent pathogen associated with respiratory disease in livestock. Respiratory cattle often involves co-infection, where primary viral infection can weaken the host immune system and thus enhance subsequent bacterial infection. The objective of this study was to investigate changes (cattle) transcriptome during bacterial-viral co-infection. RNA sequencing done whole blood cells (WBC), liver, mesenteric lymph node (MLN), tracheal-bronchial (TBLN), spleen, thymus collected from Control animals ( n = 2), infected M. (MB; 3), bovine diarrhea virus (BVDV) (Dual; 3). Results Thymus spleen had greatest number differentially expressed genes (DEGs) out all tissues analyzed. In involved maintenance extracellular matrix (ECM) including collagen type XV alpha 1 chain COL15A1 ), IV 2 COL4A2 heparan sulfate proteoglycan HSPG2 ) were most significantly downregulated Dual compared MB. thymus, complement 3 (C3) highly significant DEG upregulated Interferon inducible protein 6 IFI6 interferon-induced transmembrane proteins IFITM1 IFITM3 status Conclusion Downregulation ECM components may cause degradation contribute increased spread due Hyperactivation pathway damage influence severity Co-expression , across lymphoid be connected enhanced pathogenesis These findings suggest co-infection exacerbates through modulation coagulation cascades thymus. impacted pathways underlie thymic atrophy impaired clearance BVDV

Язык: Английский

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Immune characteristics of kidney transplant recipients with acute respiratory distress syndrome induced by COVID-19 at single-cell resolution

Respiratory Research, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 18, 2024

Abstract Background COVID-19-induced acute respiratory distress syndrome (ARDS) can result in tissue damage and multiple organ dysfunction, especially kidney transplant recipients (KTRs) receiving immunosuppressive drugs. Presently, single-cell research on ARDS is considerably advanced, yet knowledge about KTRs still constrained. Methods Single-cell RNA sequencing (scRNA-seq) analysis was performed to construct a comprehensive immune landscape of the peripheral blood mononuclear cells (PBMCs) eight patients with ARDS, five healthy individuals. Subsequently, we conducted bioinformatics analysis, including cell clustering, enrichment trajectory gene regulatory network cell–cell interaction investigate heterogeneity microenvironment ARDS. Result Our study revealed that exhibit significant compared those other individuals, reductions T cells, as well an abnormal proliferation B monocytes. In context dual influences from immunosuppression viral infection, exhibited more specific plasma along dysfunctional GZMB XAF1 double-positive effector IFI27-positive Additionally, robust communication existed among monocytes cytokine signaling. These effects impede process reconstitution KTR patients. Conclusion findings suggest show elevated antibody levels, impaired differentiation, dysregulation innate immunity. summary, this provides theoretical foundation for understanding KTRs.

Язык: Английский

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Regulation of innate immune response by miRNAs up-regulated in Stevens-Johnson syndrome with severe ocular complications

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 6, 2025

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous disorders characterized by extensive tissue necrosis; they often accompanied ocular complications (SOC). The regulatory role of microRNAs (miRNAs) in modulating immune responses SJS/TEN is not fully understood, particularly relation to chronic SOC. We explored the expression profiles specific miRNAs their potential impact on regulation key innate genes patients with analyzed plasma samples from 100 stage SOC 92 healthy controls examine levels eight (let-7a-5p, let-7d-3p, let-7e-5p, miR-146a-5p, miR-130a-3p, miR-151a-3p, miR-151a-5p, miR-27b-3p) using quantitative RT-PCR (RT-qPCR). In addition, we subjected mononuclear cells 12 9 RT-qPCR assess immune-related IFI44L, TNFSF10, AIM2, RSAD2, CXCL10, TRIM22, IFI27, IFIT2. Significant upregulation 4 was observed patients; this correlated increased TLR3, RIG-I, MDA5. Furthermore, MDA5, IFIT2 were also significantly up-regulated these patients, indicating a systemic modulation response genes. Our findings demonstrate that associated critical genes, suggesting involvement pathogenesis persistence These target may serve as biomarkers or therapeutic targets managing

Язык: Английский

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