The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease DOI Creative Commons
Agnes Carolin, David M. Frazer, Kexin Yan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 29, 2024

Abstract The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated a range comorbidities. A considerable literature suggests iron deficiency and overload may contribute to increased infection, inflammation severity, although direct causal relationships have been difficult establish. Here we generate deficient loaded C57BL/6J mice feeding low high diets, with on normal diet representing controls. All were infected primary omicron XXB SARS-CoV-2 isolate lung inflammatory responses analyzed histology, immunohistochemistry RNA-Seq. Compared controls, showed no significant changes in viral loads or histopathology, whereas, slightly, but significantly, reduced histopathology. Transcriptional modest, illustrated widespread dysregulation signatures for both vs. Some these could be associated detrimental outcomes, whereas others would viewed as beneficial. Diet-associated thus induced modest modulations signatures, histopathologically detectable exacerbations. Author summary can lead anemia, problem worldwide. excessive less common, consumption supplements. We investigate herein using mouse model, whether diets predispose outcomes lungs after infection SARS-CoV-2. promote inflammation. However, found, modulations, unaffected slightly reduced, histopathology was either indicated disease. These findings do not support view that represent comorbidities predisposing overt COVID-19

Язык: Английский

Current Advances in the Therapeutic Potential of Scutellarin: Novel Applications, Mechanisms, and Future Challenges. DOI Creative Commons
Great Iruoghene Edo, Alice Njolke Mafe, Patrick Othuke Akpoghelie

и другие.

Phytomedicine Plus, Год журнала: 2025, Номер unknown, С. 100754 - 100754

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis DOI Open Access
Vijay Kumar, John H. Stewart

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1828 - 1828

Опубликована: Фев. 2, 2024

Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, RLRs are well-characterized PRRs of the host system. cGLRs have been recently identified PRRs. In humans, cGAS/STING signaling pathway is part cGLRs. cGAS recognizes cytosolic dsDNA PAMP or DAMP STING-dependent response comprising type 1 IFN release, NF-κB activation, autophagy, cellular senescence. The present article discusses emergence critical how they regulate responses. We examined role signaling, well-studied cGLR system, in activation following sections discuss dysregulation disease cross-talk with other maintains homeostasis. This understanding will lead design better vaccines immunotherapeutics for various diseases, including infections, autoimmunity, cancers.

Язык: Английский

Процитировано

8
Immunoregulatory programs in anti‐N‐methyl‐D‐aspartate receptor encephalitis identified by single‐cell multi‐omics analysis DOI Creative Commons
Xinhui Li,

Yicong Xu,

Weixing Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract Background Anti‐ N ‐methyl‐D‐aspartate receptor encephalitis (anti‐NMDARE) is a prevalent type of autoimmune caused by antibodies targeting the NMDAR's GluN1 subunit. While significant progress has been made in elucidating pathophysiology diseases, immunological mechanisms underlying anti‐NMDARE remain elusive. This study aimed to characterize immune cell interactions and dysregulation leveraging single‐cell multi‐omics sequencing technologies. Methods Peripheral blood mononuclear cells (PBMCs) from patients acute phase healthy controls were sequenced using joint profiling transcriptome chromatin accessibility. Differential gene expression analysis, transcription factor activity profiling, cell‐cell communication modeling performed elucidate disease. In parallel, B (scBCR‐seq) repertoire analysis conducted assess antigen‐driven clonal expansion within population. Results The revealed cells, particularly plasma patients. novel finding I interferon (IFN‐I) pathway activation suggests regulatory mechanism that may drive this enhance antibody secretion. Additionally, Toll‐like 2 (TLR2) myeloid was noted, which connect tumor necrosis factor‐alpha (TNF‐α) cytokine contribute T thereby perpetuating dysregulation. Conclusions presents comprehensive characterization anti‐NMDARE, highlighting IFN‐I TLR2 pathways. These findings provide deeper insights into molecular driving pathogenesis offer promising targets for future therapeutic intervention. Key points Significant expansion, driven antigen recognition. boosts their production potentially exacerbates contributes TNF‐α secretion could influence adaptive responses.

Язык: Английский

Процитировано

1
cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values DOI Creative Commons
Danyang Zhang, Bingxue Zhang

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Gynecological cancers, including cervical, ovarian, and endometrial malignancies, remain a significant global health burden, exacerbated by disparities in access to preventive measures such as HPV vaccination routine screening. The cGAS/STING signaling pathway, pivotal mechanism innate immunity, detects cytosolic DNA from pathogens or cellular damage, triggering immune responses via type I interferons inflammatory cytokines. This pathway’s dual role gynecological either promoting antitumor immunity facilitating tumor evasion, makes it compelling target for innovative therapies. article outlines cGAS/STING’s influence on microenvironments, surveillance, inflammation, with emphasis molecular mechanisms driving cancer progression. It explores interactions between damage response pathways modulation, highlighting the impact of activation suppression cancers. therapeutic potential STING agonists, PARP inhibitors, targeted immunotherapies is reviewed, demonstrating how these approaches can boost responses, counteract chemotherapy resistance, improve patient outcomes. study also discusses strategies leveraging enhance efficacy address tumor-mediated suppression, providing insights into future directions personalized treatments.

Язык: Английский

Процитировано

1
TNF receptors: Structure-function relationships and therapeutic targeting strategies DOI
Chih Hung Lo

Biochimica et Biophysica Acta (BBA) - Biomembranes, Год журнала: 2024, Номер unknown, С. 184394 - 184394

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

7
Role of Non-coding RNAs in Rheumatoid Arthritis and Supervision Mechanism of Chinese Medicine DOI
Shu Li, Hong Fang,

Lei Wan

и другие.

Chinese Journal of Integrative Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Язык: Английский

Процитировано

0
The Role of Sustained Type I Interferon Secretion in Chronic HIV Pathogenicity: Implications for Viral Persistence, Immune Activation, and Immunometabolism DOI Creative Commons
Eman Teer, Nyasha C. Mukonowenzou, M. Faadiel Essop

и другие.

Viruses, Год журнала: 2025, Номер 17(2), С. 139 - 139

Опубликована: Янв. 22, 2025

Human immunodeficiency virus (HIV) infection induces chronic immune activation by stimulating both the innate and adaptive systems, resulting in persistent inflammation cell exhaustion. Of note, modulation of cytokine production its release can significantly influence response. Type I interferons (IFN-Is) are cytokines that play a crucial role immunity due to their potent antiviral effects, regulation IFN-stimulated genes essential for viral clearance, initiation responses. Thus, an understanding dual IFN-I (protective versus harmful) during HIV-1 infections elucidating contributions HIV pathogenesis is advancing therapeutic interventions. This review therefore delves into intricate involvement acute phases emphasizes impact on persistence, activation, immunometabolism treated HIV-infected individuals.

Язык: Английский

Процитировано

0
From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis DOI Open Access
Charlotte Delrue, Marijn M. Speeckaert

Sclerosis, Год журнала: 2025, Номер 3(1), С. 6 - 6

Опубликована: Фев. 3, 2025

Apolipoprotein L1 (APOL1) genetic variations, notably the G1 and G2 alleles, have important roles in pathophysiology of focal segmental glomerulosclerosis (FSGS) other kidney problems, especially people African descent. This review summarizes current understanding about genetic, molecular, clinical features APOL1-associated FSGS investigates new therapeutic options. It reveals how APOL1 mutations generate injury through mechanisms such as podocyte dysfunction, mitochondrial impairment, dysregulated inflammatory networks. Recent treatment developments, small-molecule inhibitors like inaxaplin, antisense oligonucleotides, novel interventions targeting lipid metabolism pathways, are being assessed for their capacity to address specific issues presented by nephropathy. We also gaps knowledge, function environmental triggers systemic consequences mutations, emphasizing significance targeted research.

Язык: Английский

Процитировано

0
Interferon-stimulated gene IFI27 as a multifaceted candidate target in precision medicine DOI Creative Commons
Maryam Shojaei, Anthony S. McLean

Trends in Immunology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

IFI27, an interferon (IFN)-stimulated gene, is emerging as a crucial player in immune responses across various species, with significant implications for precision medicine. Commonly found among the most upregulated genes infections, cancers, well inflammatory and autoimmune disorders, IFI27 ready to be trialed clinical practice certain indications, holds promise immunomodulatory target. We hypothesize that plays dual role, typically supporting defense but sometimes contributing disease progression, which might render it putative biomarker diagnosis, prognosis, treatment response. advocate focused research on unlock its potential medicine contribute unifying framework of mechanisms Our viewpoint supported by numerous studies highlighting IFI27's involvement conditions possibilities application.

Язык: Английский

Процитировано

0
Unraveling the Dual Role of circ‐CBLB and ETS‐1 in Rheumatoid Arthritis: Biomarkers and Therapeutic Targets DOI
Shu Li, Hongwei Fang, Lei Wan

и другие.

International Journal of Rheumatic Diseases, Год журнала: 2025, Номер 28(3)

Опубликована: Март 1, 2025

ABSTRACT Objective To investigate the effects of circ‐CBLB and ETS‐1 on proliferation, apoptosis, inflammatory cytokine expression in fibroblast‐like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). Methods Peripheral blood was collected 15 pairs healthy controls (HCs) RA to isolate peripheral mononuclear cells (PBMCs). mRNA determined using qRT‐PCR. Levels markers (ESR, CRP, CCP, RF) were determined, 28‐joint Disease Activity Score (DAS28) calculated. For vitro experiments, human FLS RA‐FLS cultured, constructs (pcDNA3.1/siRNA‐circ‐CBLB, pcDNA3.1/siRNA‐ETS‐1) transfected into RA‐FLS. Cotransfection pcDNA3.1‐circ‐CBLB siRNA‐ETS‐1 undertaken explore their combined effects. key cytokines (interleukin [IL]‐4, IL‐23, IL‐13, tumor necrosis factor [TNF]‐α) evaluated qRT‐PCR enzyme‐linked immunosorbent assays. Functional assays (CCK‐8) used assess cell viability, apoptosis (flow cytometry), migration. Western blotting determine protein expression. Results In vivo analysis showed significant downregulation PBMCs compared HCs, as confirmed Correlation indicated a positive association among circ‐CBLB, ETS‐1, IL‐4, while negatively correlated RF, DAS28, TNF‐α). Receiver operating characteristic curve suggested potential biomarkers for high disease activity RA. vitro, overexpression increased IL‐4 levels decreasing TNF‐α levels. Additionally, inhibited RA‐FLS, prolonged cycle, reduced regulated indicating feedback loop. Conclusion are downregulated correlate inflammation activity. They regulate each other bidirectionally. reduces promotes inhibits migration by modulating cytokines. has similar effects, interfering its reverses impact circ‐CBLB.

Язык: Английский

Процитировано

0