TNIK: A redox sensor in endothelial cell permeability.

Dysregulation of endothelial barrier integrity can lead to vascular leak and potentially fatal oedema. TNF-α controls endothelial permeability during inflammation and requires the actin organizing Ezrin-Radixin-Moesin (ERM) proteins. We identified TRAF2 and NCK-interacting kinase (TNIK) as a kinase directly phosphorylating and activating ERM, specifically at the plasma membrane of primary human endothelial cells.

CCL4 induces inflammatory signalling and barrier disruption in the neurovascular endothelium.

Background: During neuroinflammation many chemokines alter the function of the blood-brain barrier (BBB) that regulates the entry of macromolecules and immune cells into the brain. As the milieu of the brain is altered, biochemical and structural changes contribute to the pathogenesis of neuroinflammation and may impact on neurogenesis. The chemokine CCL4, previously known as MIP-1β, is upregulated in a wide variety of central nervous system disorders, including multiple sclerosis, where it is thought to play a key role in the neuroinflammatory process.

Integrated multi-omics analysis of ovarian cancer using variational autoencoders.

Cancer is a complex disease that deregulates cellular functions at various molecular levels (e.g., DNA, RNA, and proteins).

AMP-activated protein kinase is a key regulator of acute neurovascular permeability.

Many neuronal and retinal disorders are associated with pathological hyperpermeability of the microvasculature. We have used explants of rodent retinae to study acute neurovascular permeability, signal transduction and the role of AMP-activated protein kinase (AMPK). Following stimulation with either vascular endothelial growth factor (VEGF-A) or bradykinin (BK), AMPK was rapidly and strongly phosphorylated and acted as a key mediator of permeability downstream of Ca2+.

Modulation of Macrophage Function by -Conditioned Medium.

Probiotics are used as microbial food supplements for health and well-being. They are thought to have immunomodulatory effects although their exact physiological mechanism of action is not clear. This study investigated the influence of probiotic GG conditioned media (LGG-CM) on macrophage phagocytosis of non-pathogenic HfrC.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy.

GG conditioned media modulates acute reactive oxygen species and nitric oxide in J774 murine macrophages.

Phagocytes such as macrophages are capable of detecting and killing pathogenic bacteria by producing reactive oxygen and nitrogen species. Formation of free radicals in macrophages may be regulated by probiotics or by factors released by probiotics but yet to be identified. Thus, studies were carried out to determine whether cell-free conditioned medium obtained from cultures of GG (LGG-CM) regulate production of reactive oxygen species (ROS) and/or nitric oxide (NO) in macrophages.

Differential apicobasal VEGF signaling at vascular blood-neural barriers.

The vascular endothelium operates in a highly polarized environment, but to date there has been little exploration of apicobasal polarization of its signaling. We show that VEGF-A, histamine, IGFBP3, and LPA trigger unequal endothelial responses when acting from the circulation or the parenchymal side at blood-neural barriers. For VEGF-A, highly polarized receptor distribution contributed to distinct signaling patterns: VEGFR2, which was found to be predominantly abluminal, mediated increased permeability via p38; in contrast, luminal VEGFR1 led to Akt activation and facilitated cytoprotection.

Acute NADPH oxidase activation potentiates cerebrovascular permeability response to bradykinin in ischemia-reperfusion.

Free radical generation is a key event in cerebral reperfusion injury. Bradykinin (Bk) and interleukin-1β (IL-1β) have both been implicated in edema formation after stroke, although acute Bk application itself results in only a modest permeability increase. We have investigated the molecular mechanism by assessing the permeability of single pial venules in a stroke model.

Regulation of cerebromicrovascular permeability by lysophosphatidic acid.

Objective: Lysophosphatidic acid (LPA) increases permeability of cerebral endothelium in culture, but it has been suggested that histamine release is required in vivo.

Methods: Cerebral venular permeability was measured by using the single-vessel micro-occlusion technique, and fura-2 ratios were used to track changes in endothelial [Ca(2+)].

Results: Topical acute LPA application dose-dependently increased permeability (log EC(50)-9.

Quantitative assessment of medical waste generation in the capital city of Bangladesh.

There is a concern that mismanagement of medical waste in developing countries may be a significant risk factor for disease transmission. Quantitative estimation of medical waste generation is needed to estimate the potential risk and as a basis for any waste management plan. Dhaka City, the capital of Bangladesh, is an example of a major city in a developing country where there has been no rigorous estimation of medical waste generation based upon a thorough scientific study.