Journal of Biomedical Research最新文献

Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), triggers aberrant immune activation and cytokine storms, contributing to poor prognosis; however, its immune dysfunction mechanism remains unclear. Current management relies on symptomatic treatment and glucocorticoids, but no standardized treatment guidelines exist. This study investigated the mechanisms of abnormal lymphocyte function in acute-phase SFTS and the effects of glucocorticoid treatment on lymphoid cells using single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis. We enrolled three healthy volunteers and 13 patients with acute SFTS and divided them into four groups. ScRNA-seq was performed on peripheral blood mononuclear cells from all 16 participants, capturing transcripts from the 3' ends of mRNA. Bioinformatics analyses were used to profile patient immunological signatures, characterize subpopulation compositions, infer developmental trajectories, and assess lymphoid cell interactions. We obtained 120886 lymphoid cells, which were clustered into 23 functionally heterogeneous subsets. Results showed that patients with severe SFTS exhibited stronger inflammatory and adaptive immune responses. Glucocorticoid treatment suppressed inflammation and the interferon response but also inhibited the production of virus-specific antibodies. These findings suggest that appropriate glucocorticoid administration may alleviate the hyperinflammatory state in severe SFTS during the acute phase, although it is not recommended as a conventional treatment because of its potential to suppress antiviral immunity. This study provides insights into SFTS immunopathology and informs the optimized clinical use of glucocorticoids.

Neutrophils, macrophages, CD3 ⁺, CD4 ⁺, and CD8 ⁺ T lymphocytes express µ-, δ-, and κ-opioid receptors (ORs) with varying affinities for opioids. Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2 (MRGPRX2), which has a low affinity for morphine. Neutrophils and macrophages can synthesize and release endogenous opioid peptides. Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species (ROS) in unstimulated leukocytes. Conversely, OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages. Morphine inhibits Toll-like receptor 4 (TLR4) expression in macrophages, thereby attenuating inflammation, whereas methadone induces ROS production in mast cells through TLR4 activation. Stimulation of TLR4 triggers β-endorphin synthesis in macrophages. The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury. Importantly, activation of κ ₁- and µ-ORs suppresses proinflammatory cytokine production by leukocytes, thereby mitigating inflammatory injury to the heart and other organs.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by localized dilation of the abdominal aorta and a high mortality rate once rupture occurs. At present, therapeutic approaches for AAA are primarily confined to operative repair. Thus, a comprehensive understanding of its pathogenesis is crucial for the development of novel pharmacological interventions. Although the underlying mechanisms remain incompletely defined, several critical pathological features have been identified, including inflammation, extracellular matrix degradation, and loss of vascular smooth muscle cells. In recent years, perivascular adipose tissue (PVAT), an active endocrine and paracrine organ surrounding blood vessels, has emerged as an essential regulator of various cardiovascular diseases. PVAT has been shown to remodel the extracellular matrix and influence vascular smooth muscle cell behavior by establishing a pro-inflammatory milieu, thereby affecting the structural integrity and reactivity of the arterial wall. This review summarizes recent research advances in PVAT-driven inflammation in AAA and highlights the translational potential for clinical applications, aiming to provide new insights for future research.

Postoperative acute kidney injury (AKI) and postoperative delirium (POD) are two of the most common complications after surgery. It is essential to understand their common mechanisms not only to prevent and predict the occurrence of these complications, but also to guide perioperative management and improve surgical outcomes. This review summarizes the recent literature focused on these postoperative complications and explores the relationship between AKI and POD. Numerous clinical studies have used AKI and POD as primary outcomes and have found that AKI and POD often occur simultaneously in the perioperative period in susceptible groups undergoing major surgery. Some research findings indicate that the brain and the kidney exhibit bidirectional communication that is affected by systemic inflammation, drug accumulation, uremic toxins, vascular endothelial injury, and fluid volume redistribution during the perioperative period. AKI and POD share common mechanisms involving a variety of complex physiological and pathological pathways, leading to impairment of renal and cerebral function.

Medulloblastoma (MB) is the most common malignant tumor of the cerebellum in children. The SHH subgroup of MB (SHH-MB) is driven by aberrant activation of the Sonic Hedgehog (SHH) pathway; however, mutations in genes related to this pathway are relatively rare, posing challenges for therapeutic development. Glypican-6 (GPC6), a heparan sulfate proteoglycan, is highly expressed in SHH-MB. In this study, we demonstrate the synchronous expression of GPC6 with GLI1 in both the developing cerebellum and medulloblastoma. GPC6 promoted the cell proliferation, migration, and invasion in SHH-MB cell lines (DAOY and ONS-76). Consistently, GPC6 enhanced SHH pathway activity by upregulating GLI1 expression, supported ciliogenesis that is essential for signal transduction, and facilitated the secretion of SHH ligands via extracellular vesicles. These findings establish GPC6 as a critical regulator of SHH-MB progression and highlight its potential as a therapeutic target.