Inflammation Research最新文献

Objective: Ischemic heart disease (IHD) is one of the leading causes of death globally, and the process of myocardial repair after myocardial infarction (MI) is complex and crucial. Recent studies have underscored the pivotal role of cardiac-resident macrophages in the salvage of infarcted myocardium. This literature review summarizes recent findings on the central regulatory function of the activating transcription factor 3 (ATF3) in regulating macrophage behavior and macrophage-cardiomyocyte crosstalk during post-MI myocardial repair.

Methods: A comprehensive review of recent experimental and translational studies was conducted, focusing on ATF3 mediated regulation of macrophage activation, polarization, functional plasticity, and intercellular communication in the context of ischemic heart injury and repair.

Results: ATF3, a stress-responsive transcription factor, is a key mediator in oxidative stress and ischemic injury responses across diverse cellular milieus.The complexity of ATF3's role in regulating macrophage involvement in myocardial repair stems from multiple factors: the cell types expressing ATF3 can affect its function; the stage of disease progression may alter ATF3's role; and ATF3's activity is regulated not only at the expression level but also by post-translational modifications such as ubiquitination and SUMOylation. These factors collectively contribute to the intricate regulation of ATF3. Moreover, the origin of macrophages also dictates their multidimensional role in myocardial repair.

Conclusions: The ATF3-macrophage axis represents a critical regulatory network in post-MI myocardial repair. Elucidating its context dependent and cell specific mechanisms may provide novel therapeutic insights for modulating post infarction inflammation and improving cardiac repair outcomes.

Background: Asthma is the most common respiratory disorder with airway inflammation and alterations. Included among comorbidities with asthma are psychiatric conditions; however, it is unclear how these disorders engaging with each other.

Findings: In type-2-high asthma, allergens cause airway type-2 immune responses with respiratory symptoms. When the patients experience high blood levels of pro-inflammatory cytokines, they can promote reactive glial cell-induced neuroinflammation and hyperactivation of the thalamus, insula, and cingulate cortex, responsible for interoceptive states, as well as those of the hippocampus/amygdala, contributing to emotions, via the blood-cerebrospinal fluid barrier structure and cerebrospinal fluid system. The prefrontal cortex controls these brain regions to maintain cognitive responses in harmony with interoception and emotion, while over time, dysregulation of the prefrontal cortex is induced. This likely prompts cognitive-perceptual bias-related cognitive distortion or catastrophic thinking of respiratory symptoms and asthma-dependent emotions, which, rather than airway sensory hyperinnervation, may mediate uncontrollable respiratory sensory perception, leading to a spiral along with asthma symptoms.

Conclusion: Collectively, it is hypothesized that type-2 immune responses initiate airway abnormalities, while neuroinflammation and neuronal hyperactivation can induce brain neural network disruption with psychiatric episodes, presumably enhancing the progression of asthma. The notion predicts novel therapeutics for type-2-high asthma comorbid with psychiatric disorders.

The recent proposal by Xie et al. that KIAA1429 silencing ameliorates osteosarcoma progression primarily by promoting ferroptosis via the Nrf2/NQO1 axis offers a valuable yet potentially oversimplified mechanistic model. While this finding underscores the significant link between the m6A writer KIAA1429 and redox homeostasis, our critical appraisal identifies several conceptual oversights that challenge the directness and exclusivity of this pathway. The core vulnerability lies in attributing the complex phenotypic outcome of silencing a global RNA modifier to a single downstream axis, without conclusive genetic rescue evidence to establish Nrf2's indispensable role. Moreover, the pleiotropic nature of KIAA1429, which regulates a vast transcriptome encompassing other key ferroptosis regulators (e.g., GPX4, SLC7A11), is largely overlooked. The translational potential of targeting KIAA1429 is further questioned by the lack of assessment regarding on-target toxicities in normal cells, such as osteoblasts and mesenchymal stem cells, and the foreseeable resistance mechanisms via functional redundancy within the m6A machinery. This commentary urges a more nuanced interpretation of the data and highlights the formidable pharmacological challenges that must be overcome before KIAA1429 can be considered a viable therapeutic target.

The recent study by Yu et al. (2025) elucidates a critical mechanism linking mechanical stress to mitochondrial dysfunction in osteoarthritis (OA), demonstrating that Piezo1 activation is associated with impaired PINK1/Parkin-mediated mitophagy, leading to chondrocyte injury and cartilage degradation. While this work significantly advances our understanding of OA pathogenesis by integrating biomechanical and bioenergetic perspectives, key aspects require further exploration. Specifically, the downstream signaling mechanisms mediated by calcium influx, the potential role of reactive oxygen species (ROS) and inflammasome activation, and alternative therapeutic strategies beyond Piezo1 inhibition warrant deeper investigation. This commentary highlights these avenues for future research and emphasizes the importance of targeting mitochondrial quality control as a promising approach for OA therapy.

Background: B cells play a critical role in knee osteoarthritis (KOA), however, the heterogeneity, activation mechanisms, and their contribution to cartilage damage in KOA joints are still not fully understood.

Methods: We performed single-cell RNA sequencing (scRNA-seq) on joint tissues from 9 healthy controls and 21 KOA patients, integrating transcriptomic profiling, pseudotime trajectory analysis, and ligand-receptor interaction mapping. Key findings were validated using immunohistochemistry, Western blotting, in vitro co-culture systems, and a murine KOA model induced by anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT + DMM).

Results: scRNA-seq analysis identified 31 cell clusters, with B cells showing marked enrichment in subchondral bone and synovium of KOA joints, particularly in older and female patients. Re-clustering of B cells revealed eight distinct subgroups, including pathogenic DERL3⁺ and CD79B⁺B cell, which exhibited tissue-specific localization and stage-specific expansion during KOA progression. Pseudotime and regulon analyses highlighted JUN as a key transcription factor driving DERL3 ⁺ B cell differentiation. Fibroblasts emerged as critical regulators of B cell activation via MIF-(CD74 + CXCR4/CD44) signaling. Mechanistically, IL-1β-stimulated fibroblasts secreted MIF, inducing DERL3 expression in naïve B cells and may contribute to chondrocyte catabolic responses (increased MMP13, decreased COL2). Pharmacological inhibition of MIF reversed these effects in vitro and awas associated with reduced joint degeneration and improved gait and bone microarchitecture in KOA mice.

Conclusion: This study unveils a fibroblast-B cell crosstalk axis mediated by MIF signaling in KOA pathogenesis. Targeting MIF signaling may represent a promising therapeutic strategy to mitigate B cell-associated joint inflammation and structural alterations in KOA.

Triggering receptor expressed on myeloid cells 2 (TREM2), a crucial immunomodulatory receptor expressed on myeloid cells, is pivotal in regulating immune responses and maintaining tissue homeostasis. TREM2 has gained prominence as a key factor in deciphering the pathological mechanisms of diverse diseases, particularly due to its significant influence on macrophage function in disease progression. The TREM2 signaling pathway governs macrophage activation, polarization, phagocytosis, and cytokine secretion, thereby impacting immune regulation and the progression of inflammation. Dysregulation of TREM2-mediated macrophage function is closely linked to the pathogenesis of multiple systemic diseases. Specifically, in the central nervous system, extensive research has focused on TREM2's regulatory influence on microglial function. Concurrently, its pathogenic roles in disorders beyond the neurological spectrum have increasingly garnered investigative attention. This review offers a structured overview of recent advances in understanding the mechanisms through which TREM2 regulates macrophage function and its implications in non-neurological diseases. Particular emphasis is placed on the potential of TREM2 as a therapeutic target for modulating macrophage-mediated pathological processes.

Background: Pollinosis, or pollen-induced allergic rhinitis, results from complex interactions among genetic susceptibility, environmental exposures, and epigenetic regulation. Risk variants within Th2 signaling and IgE regulatory pathways (e.g., IL13, IL4R, ADAM33) have been identified, while genome-wide association and transcriptomic analyses implicate additional genes involved in immune regulation and epithelial barrier integrity. Environmental factors such as urbanization, pollen burden, and air pollution further amplify disease risk, partly through epigenetic modifications.

Methods: This narrative review synthesizes evidence from candidate-gene studies, genome-wide association studies (GWAS), transcriptomic datasets, and epigenetic investigations, with particular emphasis on gene-environment interactions in pollen-induced allergic rhinitis. We highlight replicated findings, compare results across study designs and populations, and critically appraise the strength of evidence and methodological limitations.

Results: Convergent data support the contribution of Th2-related and IgE-regulatory loci, alongside additional GWAS-implicated genes, to pollinosis susceptibility. Transcriptomic and epigenomic studies reveal dysregulated immune pathways and environmentally induced DNA methylation and chromatin changes. However, replication across ancestries is limited, variant-to-function mechanisms remain incompletely defined, and current polygenic risk scores explain only a modest proportion of disease variance. Integration of environmental metrics such as pollen load and air pollution into genetic and epigenetic models is still at an early stage.

Conclusions: Bridging molecular discoveries with environmental and clinical contexts is essential to advance precision prevention and personalized management of pollinosis. Future work should focus on fine-mapping with tissue-specific colocalization, seasonal single-cell multi-omics, and quantitative models that combine genetic risk with real-time exposure data. Clinically, polygenic risk stratification and individualized immunotherapy hold promise, but their predictive performance, feasibility, and cost-effectiveness require validation in large, ancestrally diverse cohorts.

Background: LncRNAs can regulate related miRNAs and participate in the regulation of tumorigenesis, progression, and immune escape in tumors.

Aim: To examine the clinical and functional impact of lncRNA TYMSOS in the advancement and immune escape of cervical cancer.

Methods: The abundances of TYMSOS in cervical squamous cell carcinoma (CSCC) patients were detected using RT-qPCR and verified by bioinformatic analysis. The functional impact of TYMSOS in cervical cancer cells was assessed by CCK-8 and Transwell assays. ELISA assay was utilized to determine the amounts of IFN-γ and TNF-α released. The CytoTox 96 non-radioactive cytotoxicity assay was conducted to measure the cytotoxicity of NK92 cells against cervical cancer cells. The interaction among TYMSOS, miR-134-5p, and KRAS was assessed by dual-luciferase reporter assay, RNA pull-down, and RIP assays.

Results: TYMSOS and KRAS were upregulated while miR-134-5p was decreased in CSCC patients. Serum TYMSOS levels had predictive value for CSCC patients and tumor tissue TYMSOS had prognostic value in predicting progression-free survival. Silencing TYMSOS repressed cell proliferation, migration, and invasion abilities, while enhancing the cytotoxic activity of NK cells against cervical cancer cells and stimulated the release of IFN-γ and TNF-α. miR-134-5p was a target of TYMSOS and KRAS was a potential target of miR-134-5p. Interference of KRAS abolished the effects of miR-134-5p on the malignant behaviors and killing influence of NK92 cells to cervical cancer cells.

Conclusion: Increased TYMSOS was linked to adverse prognosis, malignant progression, and immune escape in cervical cancer by modulating miR-134-5p/KRAS axis.

Background: Curcumin and Curcuma longa extract have been proposed as adjunct therapies for autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) due to their anti-inflammatory and immunomodulatory properties. The purpose of this study was to determine the effects of curcumin and Curcuma longa extract on inflammatory biomarkers in patients with RA and SLE.

Methods: PubMed, EMBASE, and Cochrane CENTRAL databases were searched to May 14, 2025. Randomized controlled trials (RCTs) comparing curcumin or Curcuma longa extract with placebo or standard therapy in patients with RA or SLE were included. The primary outcomes were changes in disease activity score (DAS-28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level analyzed using standardized mean differences (SMDs) with a random-effects model. Heterogeneity was assessed using the I² statistic, and sensitivity analyses were conducted using a leave-one-out approach.

Results: Seven RCTs involving 314 patients were included. The meta-analysis revealed no significant effect of curcumin or Curcuma longa extract on DAS-28 (pooled SMD = - 2.34, 95% confidence level [CI]: - 5.13 to 0.44; I² = 96.0%), ESR (pooled SMD = - 1.49, 95% CI - 3.71 to 0.72; I² = 91.7%), or CRP (pooled SMD = - 1.65, 95% CI - 3.88 to 0.58; I² = 91.6%). Substantial heterogeneity was observed across all outcomes.

Conclusions: This meta-analysis suggests that curcumin and Curcuma longa extract have limited and inconsistent effects on inflammatory biomarkers in patients with RA and SLE. Larger, well-designed RCTs are needed to clarify their clinical utility as adjunct therapies.

Background: Kinins, bioactive peptides produced through the proteolytic activity of kallikrein1, are members of the kallikrein-kinin system (KKS) and play crucial roles in regulating physiological processes such as inflammation, blood pressure, vascular permeability, and cell function and growth. In adipose tissue, bradykinin (BK) and des-Arg9-BK (DBK), produced by plasma kallikrein (KLKB1), act via their receptors B2 (B2R) and B1 (B1R), respectively. B1R predominates in preadipocytes, while B2R is expressed during adipogenesis, likely driving adipose tissue expansion and sustaining chronic low-grade inflammation, both hallmarks of obesity and its associated metabolic disorders. Obesity, a multifactorial metabolic disease, is closely linked to adipose tissue dysfunction. This dysfunction is driven by inflammation and oxidative stress, which in turn alter adipogenesis, lipolysis, and insulin and leptin signaling, contributing to obesity and its comorbidities.

Purpose: This review focuses on the role of the KKS in adipose tissue homeostasis and function.

Findings: Evidence from animal models suggests that B1R ablation or antagonism results in a healthier phenotype, characterized by improved leptin and insulin sensitivity, increased lipid oxidation, reduced adipose hypertrophy, and diminished production of proinflammatory mediators and reactive oxygen species. Conversely, B2R activation may exert protective effects by enhancing insulin signaling and promoting glucose uptake, although its role remains incompletely understood and appears context-dependent.

Conclusion: The KKS proposes it as a promising therapeutic target, biomarker, and prognostic indicator in anti-obesity pharmacological strategies.