Annals of medicine
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Peroxisome biogenesis disorders (PBD) affect multiple organ systems. It is characterized by neurological dysfunction, hypotonia, ocular anomalies, craniofacial abnormalities, and absence of peroxisomes in fibroblasts. PBDs are associated with mutations in any of fourteen different PEX genes, which are involved in peroxisome biogenesis. Zellweger spectrum disorder (ZSD) is a severe form of PBD. More than 90% of the ZSD cases have mutations in PEX1, PEX6, PEX10, PEX12, and PEX26. Mutations in the PEX19 gene are rarely associated with PBD/ZSD; however, a large proportion of PEX26 mutations are associated with ZSD. ⋯ The present study has added a novel nonsense mutation to the mutation spectrum of PEX19, which is the second null mutation identified to date. Moreover, in this study, the importance of a synonymous exonic variant of PEX26 close to the splice donor site was explored in relation to pre-mRNA splicing and resulting disease manifestations.
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The prognosis for severe asthma is poor, and the current treatment options are limited. The methyl-CpG binding domain protein 2 (MBD2) participates in neutrophil-mediated severe asthma through epigenetic regulation. Neutrophil extracellular traps (NETs) play a critical role in the pathogenesis of severe asthma. This study aims to detect if MBD2 can reduce NETs formation and the potential mechanism in severe asthma. ⋯ MBD2 regulates PAD4 expression through the JAK2 signaling pathway to promote NETs formation in mice with severe asthma. Further bench-based and bedside-based studies targeting the MBD2, PAD4, and JAK2 signaling pathways will help open new avenues for drug development of severe asthma.
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Meta Analysis
Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis.
Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength. ⋯ HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.
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Unlike the commonly seen uphill esophageal varices in clinical practice, downhill esophageal varices are caused by obstruction of the superior vena cava and azygous venous system. The predominant causes of downhill esophageal varices are hemodialysis in end-stage renal disease patients and mediastinal malignancies. The cornerstone of the treatment for downhill esophageal varices is to address the underlying primary causes. Without this, patients may suffer from recurrent bleeding, and the bleeding can be fatal. ⋯ Specifically, when varices are only observed in the upper and middle esophagus, and the patient presents with evidence of superior vena cava obstruction, clinicians should be particularly vigilant for downhill esophageal varices. Moreover, a thorough investigation and definitive treatment of the underlying primary causes should be implemented.
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Atherosclerosis is a leading cause of global mortality, driven by complex interactions between genetic, metabolic, and environmental factors. Among these, hyperhomocysteinemia (HHcy) has emerged as a significant and modifiable risk factor, contributing to endothelial dysfunction, oxidative stress, and vascular inflammation. Despite increasing recognition of its role in atherogenesis, the precise mechanisms and clinical implications of HHcy remain incompletely understood, necessitating a comprehensive review to connect recent mechanistic insights with practical applications. ⋯ This review consolidates and elucidates the latest advancements and insights into the role of HHcy in atherosclerosis. The comprehensive narrative connects fundamental research with clinical applications. Contemporary studies highlight the complex interplay between HHcy and atherosclerosis, establishing HHcy as not only a contributing risk factor but also an accelerator of various atherogenic processes.