Frontiers of Medicine最新文献

Acute lung injury (ALI) is a respiratory disease characterized by inflammation. Yinqiao powder (YQP) is a traditional Chinese medicinal compound, extensively used for its heat-clearing and detoxifying effects. It is usually used clinically to treat respiratory diseases, such as pneumonia. However, the exact mechanism by which YQP treats ALI remains unclear. Here, we aimed to explore the therapeutic effects and potential mechanisms of action of YQP in ALI. Activation of the cGAS-STING pathway was modeled by multiple stimuli in bone marrow-derived macrophages (BMDMs), THP-1, and peripheral blood mononuclear cells (PBMCs). Changes in the content of associated proteins were detected by Western blot, while the mRNA levels of type I interferon-related genes and proinflammatory cytokines were detected by qPCR. A DMXAA-induced agonist model was used to verify the effect of YQP on the cGAS-STING pathway in vivo, whereas LPS-induced ALI was used to explore the therapeutic effect of YQP. YQP suppressed the activation of the cGAS-STING pathway in vitro. YQP showed promising therapeutic effects on DMXAA-induced activation of the cGAS-STING signaling pathway as well as the LPS-induced ALI model in mice. YQP alleviated ALI by inhibiting cGAS-STING pathway activation; meanwhile, YQP may be a new therapeutic approach for cGAS-STING-driven inflammatory diseases.

Cardiovascular disease remains the foremost contributor to mortality and disability globally, even with significant advancements in prevention, diagnosis, and early intervention. A comprehensive insight into cardiovascular diseases and the intrinsic molecular mechanisms is critical to innovating more effective therapeutic interventions for prevention and therapy. Latest advancements within the realm of epigenetic modulation, especially methylation modification, of gene expression have corroborated the impacts of epigenetic modifications in governing the pathogenesis and progression of cardiovascular diseases and suggested the viability of epigenetic mechanisms as emerging targets for the development of new diagnostic and therapeutic strategies. In this review, we first provide a brief overview of the biological processes of methylation modifications, including DNA methylation, protein methylation, and RNA N⁶-methyladenosine (m⁶A) modification. We then summarize their roles in cardiac hypertrophy, heart failure, ischemic heart disease, and atherosclerosis.

Aspartate/asparagine-β-hydroxylase (ASPH), a type II transmembrane α-ketoglutarate-dependent hydroxylase, is frequently overexpressed in various cancers. However, its role in lung adenocarcinoma (LUAD) remains unclear. Here, we analyzed ASPH expression in LUAD and normal lung tissues using bioinformatic tools, and evaluated its association with clinicopathological characteristics and patient prognosis. High ASPH expression correlated with advanced disease and poor survival, and served as an independent prognostic factor. Functional assays, including Transwell, scratch healing, and murine lung metastasis models, demonstrated that ASPH promotes LUAD cell migration and metastasis. The potential molecular mechanisms by which ASPH exerts its function in LUAD were explored by transcriptome sequencing analysis and immunoprecipitation combined with mass spectrometry (IP-MS). Further analysis showed that ASPH enhances activation of the MAPK and Notch signaling pathways through RUVBL2 interaction. Collectively, our findings suggest that ASPH contributes to LUAD progression by engaging RUVBL2 and activating key oncogenic signaling cascades, highlighting its potential as a prognostic biomarker and therapeutic target.

Given the maternal hypercoagulability during pregnancy, thrombophilia may increase the risk of adverse pregnancy outcomes (APOs). This retrospective case-control study aimed to assess whether low-molecular-weight heparin (LMWH) could improve APOs in women with protein S (PS) deficiency. We selected 35 pregnant women who were considered for potential PS deficiency, and 70 healthy pregnant women were randomly selected as the control group. Two or more consecutive miscarriages were more frequent in pregnant women with PS deficiency than in the control group (12/35 vs. 4/70, P = 0.0001). Ten pregnant women with PS deficiency conceived by in vitro fertilization-embryo transfer (IVF-ET), which was significantly higher than the number of controls who conceived by IVF-ET (4/70, P = 0.0012). All 20 women in the LMWH-treated group (P = 0.001) had live births, which were significantly higher than that in the LMWH-untreated group (8/15, 53.3%). In the subgroup aged ⩽ 32 years of age, the number of live births in both groups was 7 (7/7, 100%) and 7 (7/12, 58.3%), respectively (P = 0.106). In conclusion, impediments to spontaneous conception and an elevated incidence of pregnancy loss may be associated with PS deficiency. Furthermore, the elevated live birth rate might be attributable to the administration of LMWH during gestation.

Chimeric antigen receptor T-cell (CAR-T) therapy has been successfully applied in clinical treatment, especially for hematologic malignancies such as multiple myeloma (MM), but its broad application is limited by cytokine release syndrome (CRS), a potentially life-threatening complication. Although metabolic alterations are known to accompany CRS, predictive biomarkers for its onset, severity, and associated metabolic remodeling remain unknown, hindering proactive clinical management. Here, we analyzed longitudinal serum metabolic profiles from 19 patients with relapsed/refractory MM receiving CAR-T therapy, with validation in an independent cohort of 23 patients. We observed dysregulated arginine metabolism that progressed alongside clinical CRS. At pre-lymphodepletion (Day-5), over half of differentially abundant metabolites were enriched in unsaturated fatty acid (UFA) synthesis pathways, which were exclusively upregulated in patients who later developed severe CRS. Furthermore, two lysophosphatidylcholines, namely, lysoPC(16:0) and lysoPC(15:0), were significantly associated with delayed CRS onset, with elevated concentrations correlated with a prolonged time to onset; this association was independently validated. These findings revealed that arginine metabolism was a pathological axis in CRS, UFAs were severity predictors, and specific lysoPCs were modulators of onset time. Collectively, they provide proactive CRS management, addressing critical gaps in predictive biomarkers to advance the safe, broad CAR-T application in MM.

Extensive bone defects represent a significant clinical challenge, often leading to severe impairment of patients function and quality of life. Traditional treatments, such as autografts and allografts, are widely used but have notable limitations, including donor site morbidity and immunogenicity. As a result, tissue engineering has attracted increasing attention as a viable alternative. Bioceramic bone repair materials provide both mechanical support and bioactive functions in the treatment of bone defects. They modulate the immune microenvironment to promote cellular behaviors and signaling pathways conducive to bone regeneration. The immunoregulatory effects of these materials play a critical role throughout the bone repair process and are pivotal in determining the success of regeneration. For instance, hydroxyapatite can induce the polarization of macrophages towards the M2 phenotype, exerting anti-inflammatory effects that promote bone tissue repair. This review summarizes recent advancements in the research of bioceramics for bone tissue engineering, with a focus on the classification of bioceramic materials, their immunomodulatory mechanisms in bone regeneration, current fabrication techniques, and the status of clinical translation. We aim to provide insights that support future research and the development of improved strategies for bone defect repair.

Chimeric antigen receptor T (CAR-T) cells demonstrate remarkable effectiveness in targeting and eliminating pathogenic B-cell lineages, showing significant specificity and efficacy against B cell malignancies. In addition, CAR-T cell-mediated B cell depletion and resetting, which showed great potential in treating autoimmune diseases, thereby extending the clinical applicability of adoptive cell therapy. In this review, we examine the progression of CAR-T targeted B cell therapy for autoimmune diseases, encompassing the development of new therapeutic strategies and reports on related clinical outcomes. Furthermore, the article delves into the challenges and potential avenues for enhancement related to the safety aspects and inherent limitations of current technological solutions.

Mitochondrial disorders are highly heterogeneous and can manifest as a spectrum of clinically heterogeneous disorders that affect multiple organ systems. Herein, we report a Chinese female patient carrying mitochondrial DNA m.3243A>G mutation who sequentially experienced myoclonic epilepsy with ragged red fibers, mitochondrial neurogastrointestinal encephalomyopathy, and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. This report expands the current understanding of phenotypic heterogeneity in mitochondrial disorders.

Atherosclerosis is a chronic inflammatory disease driven by pathological processes such as macrophage foam cell formation. Semaphorin 7A (SEMA7A) is an immunoregulatory signaling molecule known to modulate immune responses and cellular adhesion. However, the contribution of macrophage-derived SEMA7A to atherogenesis has yet to be fully elucidated. In this study, we analyzed gene expression profiles of human mononuclear cells from the Gene Expression Omnibus (GEO) database and revealed highly expressed SEMA7A and its receptor integrin β1 in macrophages. The upregulation of SEMA7A and integrin β1 was also observed during the differentiation of THP-1 monocytes into macrophages. Mice with macrophage-specific deletion of Sema7a showed a 57.2% reduction in atherosclerotic lesion size and improved plaque stability in atherosclerosis mouse model compared to control mice. Mechanistically, macrophage SEMA7A promoted the expression of macrophage scavenger receptor 1 (MSR1) and lipid uptake mediated by integrin β1 and downstream JNK signaling pathway in macrophages. Notably, pharmacological inhibition of integrin β1 with integrin receptor antagonist GLPG0187 effectively suppressed atherosclerosis progression. These findings identify macrophage-derived SEMA7A as a key driver of atherosclerosis through a novel integrin β1/JNK/MSR1 axis, providing potential targets for the prevention and treatment of atherosclerosis.