Journal of Biomedical Research最新文献

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.

Neutralizing antibodies are essential tools in antiviral therapy and epidemic preparedness, capable of directly inhibiting viral entry and limiting disease progression. However, traditional antibody discovery strategies-such as animal immunization or B cell isolation from infected individuals-are often hindered by biosafety concerns, lengthy development timelines, and limited adaptability during outbreaks. In the present study, we aimed to establish a robust and rapid in vitro platform for the efficient isolation of neutralizing antibodies targeting conserved viral epitopes. We developed an epitope-guided negative screening strategy that integrate phage display technology with rational antigen mutagenesis to exclude antibodies against variable regions while enriching those that recognize functionally constrained epitopes. When applied to the receptor-binding domain (RBD) of SARS-CoV-2, this method enabled the identification of six neutralizing antibodies (one IgG and five nanobodies) exhibiting broad-spectrum neutralizing activity across multiple viral variants. Notably, antibodies recognizing distinct epitopes demonstrated significant synergistic neutralization when used in combination ( P < 0.05). This screening approach facilitates the rapid discovery of potent and mutation-resistant antibodies and holds promise for applications to other emerging pathogens. Our findings underscore the potential of epitope-guided, in vitro platforms in expediting therapeutic antibody development under conditions of high biosafety requirement.

This study aimed to characterize frequency- and latency-dependent network dysregulation in migraine using magnetoencephalography (MEG)-based static and dynamic functional connectivity analyses during auditory stimulation. Thirty interictal migraine patients and 30 matched healthy controls underwent whole-head MEG recordings during a lateralized auditory task. Static and dynamic functional connectivities were calculated using the corrected amplitude envelope correlation in seven canonical frequency bands (delta 2-120 Hz). Group differences were examined using nonparametric permutation tests, with false discovery rate and Bonferroni correction applied to account for multiple comparisons. Static functional connectivity abnormalities were confined to high-frequency bands (low-gamma, 30-59 Hz; high-gamma, 60-90 Hz; and ripple, 90-120 Hz), showing enhanced frontal-limbic and cross-hemispheric connectivity in migraine patients (Cohen's d = 1.05-1.37). Low-frequency bands showed no significant differences. Dynamic functional connectivity revealed rapid, frequency-specific abnormalities: early (25-50 ms) gamma/ripple hyperconnectivity and late delta/beta alterations, with hemispheric asymmetry. Thus, migraine is characterized by high-frequency oscillatory imbalance during auditory processing, with both persistent (static) and transient (dynamic) network disruptions concentrated in gamma/ripple bands, consistent with impaired predictive coding and sensory hypersensitivity.

A major threat to the global human population is zoonosis, which refers to viral infections transmitted from animals. Pigs are crucial to the transmission of the influenza A virus (IAV) because they express both human-type (α-2,6-linked) and avian-type (α-2,3-linked) sialic acid (SA) receptors, making them a direct source of zoonosis and providing essential "mixing vessels" for avian and swine viruses. We aimed to mitigate the IAV threat by disrupting pig influenza infection through gene targeting of the viral receptors in pigs. We utilized CRISPR/Cas9 to knock out the ST6GAL1 and ST3GAL4 genes, which encode enzymes responsible for synthesizing both the human and avian SA receptors in pigs. We observed a significant reduction in these SA receptors in the respiratory tract of the genetically modified pigs. The deletion of these genes conferred partial resistance to IAV infection in vitro, substantially decreasing viral susceptibility. Post-infection transcriptomic analysis revealed distinct expression profiles in ST6GAL1 ^-/- /ST3GAL4 ^-/- pigs compared with those of wild-type pig cells. Creating ST6GAL1 ^-/- /ST3GAL4 ^-/- pigs provides a large-animal model for studying cross-species transmission of IAV, offering a novel strategy to reduce pandemic risks by disrupting influenza transmission between pigs and humans. This approach suggests a new method for controlling pandemics by targeting animals rather than humans, making it potentially safer than many current alternatives.