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Function: require_once
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: str_replace
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Vascular endothelial (VE)-cadherin, a major endothelial adhesion molecule, regulates vascular permeability, and increased vascular permeability has been observed in several cancers. The aim of this study was to elucidate the role of the NEDD8-Cullin E3 ligase, in maintaining barrier permeability. To this end, we investigated the effects of the inhibition of Cullin E3 ligases, by using inhibitors and knockdown techniques in HUVECs. Furthermore, we analyzed the mRNA and protein levels of the ligases by quantitative RT-PCR and Western blotting, respectively. The results revealed that NEDD8-conjugated Cullin 3 is required for VE-cadherin-mediated endothelial barrier functions. Treatment of HUVECs with MLN4924, a chemical inhibitor of the NEDD8-activating enzyme, led to high vascular permeability due to impaired cell-cell contact. Similar results were obtained when HUVECs were treated with siRNA directed against Cullin 3, one of the target substrates of NEDD8. Immunocytochemical staining showed that both treatments equally depleted VE-cadherin protein localized at the cell-cell borders. However, quantitative RT-PCR showed that there was no significant difference in the VE-cadherin mRNA levels between the treatment and control groups. In addition, cycloheximide chase assay revealed that the half-life of VE-cadherin protein was dramatically reduced by Cullin 3 depletion. Together, these findings suggest that neddylated Cullin 3 plays a crucial role in endothelial cell barrier function by regulating VE-cadherin.
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http://dx.doi.org/10.1111/cas.13133 | DOI Listing |
J Transl Med
December 2024
Institut de Recherche Biomédicale Des Armées (IRBA), 1, Rue du Lieutenant Raoul Batany, 92141, Clamart, France.
Background: Hemorrhagic shock (HS) corresponds to absolute hypovolemia creating an imbalance between oxygen supply and consumption. This causes an impaired hemostasis, a systemic inflammatory response, and microvascular permeability which can lead to multiple organ failure (MOF). There is no specific treatment for the endothelial dysfunction that plays a major role in the evolution towards MOF.
View Article and Find Full Text PDFOphthalmol Sci
October 2024
Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, New Jersey.
Objective: To investigate retinal vascular permeability mapping as a potential biomarker for diabetic retinopathy in subjects with diabetes with no signs of retinopathy and with mild nonproliferative retinopathy.
Design: This is a case-control study.
Subjects: Participants included 7 healthy controls, 22 subjects with diabetes mellitus and no clinical signs of retinopathy (DMnoDR), and 7 subjects with mild nonproliferative diabetic retinopathy (NPDR).
J Control Release
December 2024
Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent CRIG, Ghent, Belgium. Electronic address:
Tumor fluid dynamics and drug delivery simulations in solid tumors are highly relevant topics in clinical oncology. The current study introduces a novel method combining computational fluid dynamics (CFD) modeling, quantitative magnetic resonance imaging (MRI; including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted (DW) MRI), and a novel ex-vivo protocol to generate patient-specific models of solid tumors in four patients with peritoneal metastases. DCE-MRI data were analyzed using the extended Tofts model to estimate the spatial distribution of tumor capillary permeability using the K parameter.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Background: The global incidence of type 2 diabetes (T2D) is rapidly increasing, with retinopathy being its most common complication and a leading cause of preventable blindness. Although the precise mechanisms involved in the development of diabetic retinopathy (DR) are not fully understood, defective immunomodulation is a recognized key factor in its pathophysiology. Regulatory T cells (Treg) regulate inflammation and promote regeneration, and while they are known to have important anti-inflammatory and neuroprotective roles in other tissues, including central nervous system, their role in the diabetic retina remains largely unknown.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Critical Care Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Sepsis is a clinical syndrome resulting from the interaction between coagulation, inflammation, immunity and other systems. Coagulation activation is an initial factor for sepsis to develop into multiple organ dysfunction. Therefore, anticoagulant therapy may be beneficial for sepsis patients.
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