Metformin alleviates lung-endothelial hyperpermeability by regulating cofilin-1/PP2AC pathway.

Microvascular endothelial hyperpermeability is an earliest pathological hallmark in Acute Lung Injury (ALI), which progressively leads to Acute Respiratory Distress Syndrome (ARDS). Recently, vascular protective and anti-inflammatory effect of metformin, irrespective of glycemic control, has garnered significant interest. However, the underlying molecular mechanism(s) of metformin's barrier protective benefits in lung-endothelial cells (ECs) has not been clearly elucidated.

Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial.

Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS).

Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer.

Design, Setting, And Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites.

Acoustics of Emotional Prosody Produced by Prelingually Deaf Children With Cochlear Implants.

: Cochlear implants (CIs) provide reasonable levels of speech recognition quietly, but voice pitch perception is severely impaired in CI users. The central question addressed here relates to how access to acoustic input pre-implantation influences vocal emotion production by individuals with CIs. The objective of this study was to compare acoustic characteristics of vocal emotions produced by prelingually deaf school-aged children with cochlear implants (CCIs) who were implanted at the age of 2 and had no usable hearing before implantation with those produced by children with normal hearing (CNH), adults with normal hearing (ANH), and postlingually deaf adults with cochlear implants (ACI) who developed with good access to acoustic information prior to losing their hearing and receiving a CI.

miR-144-mediated Inhibition of ROCK1 Protects against LPS-induced Lung Endothelial Hyperpermeability.

Dysfunctional endothelial cell (EC) barrier and increased lung vascular permeability is a cardinal feature of acute lung injury and sepsis that may result in a pathophysiological condition characterized by alveolar flooding, pulmonary edema, and subsequent hypoxemia. In lung ECs, activation of Rho-associated kinase-1 (ROCK1) phosphorylates myosin light chain (MLC)-associated phosphatase at its inhibitory site, which favors phosphorylation of MLC, stress fiber formation, and hyperpermeability during acute lung injury. The role of microRNA-144 (miR-144) has been well investigated in many human diseases, including cardiac ischemia/reperfusion-induced injury, lung cancer, and lung viral infection; however, its role in pulmonary EC barrier regulation remains obscure.

Erythropoietin-mediated activation of aquaporin-4 channel for the treatment of experimental hydrocephalus.

Objective: In this study, we investigate a neuroprotective agent, erythropoietin (EPO), in animal hydrocephalus model and its potential reversal effects on hydrocephalus by altering the expression of aquaporin-4 (AQP4).

Methods: Obstructive hydrocephalus was induced in 2-week-old rat pups by injecting kaolin (50 μl, 10 mg/ml in saline) into the cisterna magna, while the control pups received only saline. Kaolin-injected pups were divided into two groups on the fifth day after kaolin injection; one group received intra-peritoneal (i.

Folate receptor alpha is more than just a folate transporter.

Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of , and genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules.

Folate Receptor Alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells.

Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor.

Angiopoietin-1 Regulates Brain Endothelial Permeability through PTPN-2 Mediated Tyrosine Dephosphorylation of Occludin.

Objective: Blood brain barrier (BBB) breakdown and increased endothelial permeability is a hallmark of neuro-vascular inflammation. Angiopoietin-1 (Ang-1), a Tie-2 receptor agonist ligand, is known to modulate barrier function of endothelial cells; however the molecular mechanisms related to Ang-1 mediated repair of Tight Junctions (TJs) in brain endothelium still remain elusive. In this study, we investigated a novel role of non-receptor protein tyrosine phosphatase N-2 (PTPN-2) in Ang-1 mediated stabilization of tight junction proteins.

A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 -/- embryos.

Purpose: Maternal folate intake has reduced the incidence of human neural tube defects by 60-70 %. However, 30-40 % of cases remain nonresponsive to folate intake. The main purpose of this study was to understand the molecular mechanism of folate nonresponsiveness in a mouse model of neural tube defect.

Evidence of a common mechanism of disassembly of adherens junctions through Gα13 targeting of VE-cadherin.

The heterotrimeric G protein Gα13 transduces signals from G protein-coupled receptors (GPCRs) to induce cell spreading, differentiation, migration, and cell polarity. Here, we describe a novel GPCR-independent function of Gα13 in regulating the stability of endothelial cell adherens junctions (AJs). We observed that the oxidant H2O2, which is released in response to multiple proinflammatory mediators, induced the interaction of Gα13 with VE-cadherin.

Caveolin-1-eNOS signaling promotes p190RhoGAP-A nitration and endothelial permeability.

Endothelial barrier function is regulated by adherens junctions (AJs) and caveolae-mediated transcellular pathways. The opening of AJs that is observed in caveolin-1(-/-) (Cav-1(-/-)) endothelium suggests that Cav-1 is necessary for AJ assembly or maintenance. Here, using endothelial cells isolated from Cav-1(-/-) mice, we show that Cav-1 deficiency induced the activation of endothelial nitric oxide synthase (eNOS) and the generation of nitric oxide (NO) and peroxynitrite.

Results of endovascular therapy and aortobifemoral grafting for Transatlantic Inter-Society type C and D aortoiliac occlusive disease.

Objective: The purpose of this study was to compare the outcomes of aortoiliac stenting (AIS) to those of aortobifemoral grafting (ABF) for patients with TransAtlantic Inter-Society Consensus (TASCII) C and D aortoiliac occlusive disease.

Methods: From 1998 to 2007, 32 patients underwent ABF and 40 patients underwent AIS. Kaplan-Meier estimates for patency were used.