Translational research : the journal of laboratory and clinical medicine
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Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. ⋯ Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.
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The present study aimed to quantify the magnitude of the systemic inflammatory response, measured by C-reactive protein (CRP) and albumin, and its relationship with common serum biochemical measures of iron status including total iron, transferrin, transferrin saturation, and ferritin. Retrospective interrogation of laboratory computer databases at 4 centers between 2006 and 2011 provided results from patients in which serum CRP and albumin had been measured together with iron studies (iron, transferrin, and transferrin saturation, n = 16,522) and ferritin (n = 7,226). Analyte results were categorized into groups according to CRP and albumin. ⋯ The median serum ferritin was 77, 173, and 445 μg/L respectively (P < 0.001), an overall increase of 578%. The present study quantifies the impact of the systemic inflammatory response on serum measures of iron status. This association should be taken into account when measures of iron status are requested and interpreted to prevent misdiagnosis.
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Atherosclerosis is a mechanobiology-related disease that preferentially develops in the aortic arch and arterial branches, which are exposed to disturbed/turbulent blood flow but less in thoracic aorta where the flow pattern is steady laminar flow (LF). Increasing evidence supports that steady LF with high shear stress is protective against atherosclerosis. However, the molecular mechanisms of LF-mediated atheroprotection remain incompletely understood. ⋯ Furthermore, we found in apolipoprotein E deficient (ApoE(-/-)) mice and human ECs, LF decreased the level of nuclear YAP protein and YAP target gene expression (connective tissue growth factor and cysteine-rich protein 61) through promoting Hippo kinases LATS1/2-dependent YAP (Serine 127) phosphorylation. Functionally, we revealed that YAP depletion in ECs phenocopying LF responses, reduced the expression of cell cycle gene cyclin A1 (CCNA1) and proinflammatory gene CCL2 (MCP-1). Taken together, we demonstrate that atheroprotective LF inhibits endothelial YAP activation, which may contribute to LF-mediated ECs quiescence and anti-inflammation.
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Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (∼1 ms) and good spatial precision (∼3-5 mm). In a typical experiment, MEG data are acquired as healthy controls or patients with neurologic or psychiatric disorders perform a specific cognitive task, or receive sensory stimulation. The resulting data are generally analyzed using standard electrophysiological methods, coupled with advanced image reconstruction algorithms. ⋯ This review focuses on the clinical areas where MEG imaging has arguably had the greatest impact in regard to the identification of aberrant neural dynamics at the regional and network level, monitoring of disease progression, determining how efficacious pharmacologic and behavioral interventions modulate neural systems, and the development of neural markers of disease. Specifically, this review covers recent advances in understanding the abnormal neural oscillatory dynamics that underlie Parkinson's disease, autism spectrum disorders, human immunodeficiency virus (HIV)-associated neurocognitive disorders, cerebral palsy, attention-deficit hyperactivity disorder, cognitive aging, and post-traumatic stress disorder. MEG imaging has had a major impact on how clinical neuroscientists understand the brain basis of these disorders, and its translational influence is rapidly expanding with new discoveries and applications emerging continuously.
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Limited information is available on the pathologic significance of human antigen R (HuR) in prostate cancer (PCa). The main aim of this study was to clarify the relationship between HuR expression and malignant aggressiveness, outcome, and expression of cancer-related molecules in PCa. In vitro proliferation, colony formation, and migration assays were performed on LNCaP and PC-3 cells. ⋯ C-HuR expression was positively associated with Gleason score, T stage, and metastasis, and it was considered to be a useful predictor of biochemical recurrence after radical prostatectomy. C-HuR expression was correlated with COX-2 expression in hormone-naïve PCa, and with the expression of VEGF-A, VEGF-C, and COX-2 in CRPC tissues. Our results demonstrated that HuR plays important roles in determining malignant aggressiveness and outcome in PCa, especially in androgen-independent PCa cells, via the regulation of cell proliferation, migration, and expression of VEGF-A, -C, and COX-2.