RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that induces cytokine hypersecretion. Receptor activity-modifying protein (RAMP) 1, a subunit of the calcitonin gene-related peptide (CGRP) receptor, regulates the production of cytokines. This study examined the role of RAMP1 signaling during lipopolysaccharide (LPS)-induced acute lung injury (ALI).

VEGFR1 TK signaling protects the lungs against LPS-induced injury by suppressing the activity of alveolar macrophages and enhancing the anti-inflammatory function of monocyte-derived macrophages.

Acute lung injury (ALI) is characterized by hyperinflammation followed by vascular leakage and respiratory failure. Vascular endothelial growth factor (VEGF)-A is critical for capillary permeability; however, the role of VEGF receptor 1 (VEGFR1) signaling in ALI progression remains unclear. Here, we show that deletion of VEGFR1 tyrosine kinase (TK) signaling in mice exacerbates lipopolysaccharide (LPS)-induced ALI as evidenced by excessive pro-inflammatory cytokine production and interleukin(IL)-1β-producing neutrophil recruitment to inflamed lung tissues.

Life-threatening traumatic epistaxis due to massive bleeding into the maxillary sinus.

A 77-year-old woman with no medical history fell, and her face was strongly impacted on the ground. On arrival at our hospital, her initial vital signs were stable. She underwent an endoscopy to stop the bleeding.

Pancreatitis in a Patient with Severe Coronavirus Disease Pneumonia Treated with Veno-venous Extracorporeal Membrane Oxygenation.

Severe coronavirus disease (COVID-19) can induce serious complications, including acute respiratory distress syndrome, septic shock, and acute kidney injury. However, few reports have associated COVID-19 with pancreatitis. We herein report the case of a 55-year-old patient who developed acute pancreatitis associated with severe COVID-19 pneumonia and was successfully treated with veno-venous extracorporeal membrane oxygenation (ECMO).

Bisphenol A binds to protein disulfide isomerase and inhibits its enzymatic and hormone-binding activities.

Bisphenol A [2,2-bis-(4-hydroxyphenyl) propane; BPA] is a versatile industrial material for plastic products, but is increasingly being recognized as a pervasive industrial pollutant as well. Accumulating evidence indicates that the environmental contaminant BPA is one of the endocrine-disrupting chemicals that potentially can adversely affect humans as well as wildlife. To define the molecular aspects of BPA action, we first investigated the molecules with which it physically interacts.

Production of inhibitory polyclonal antibodies against cytochrome P450s.

Nine different antibodies against P450 isoforms were prepared using purified cytochrome P450s (P450) expressed in E. coli. Purified isozymes were injected into rabbits to raise specific antibody.

Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha protein.

Apigenin, a plant-derived flavone, is a potent inhibitor of cell proliferation and angiogenesis, but the mechanisms leading to the pathological anti-angiogenic effects of apigenin are still unclear. In this study, we found that apigenin inhibited the hypoxia-induced expression of vascular endothelial growth factor (VEGF) mRNA in human umbilical artery endothelial cells. Apigenin also suppressed the expression of erythropoietin mRNA, which is a typical hypoxia-inducible gene, via the degradation of hypoxia-inducible factor 1 (HIF-1) alpha.

Bisphenol A, an environmental endocrine-disrupting chemical, inhibits hypoxic response via degradation of hypoxia-inducible factor 1alpha (HIF-1alpha): structural requirement of bisphenol A for degradation of HIF-1alpha.

Bisphenol A (BpA), an endocrine-disrupting chemical, is known to be a xenoestrogen and to affect the reproductive functions of animals. Recent reports have documented BpA-induced developmental abnormalities in the neuronal systems of humans and animals, and these effects appear to be non-estrogenic. In this study, we found that BpA inhibited the hypoxic response of human hepatoma cells.

Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation.

We investigated the biological effects of the active oxygen produced by P450s. First, we identified which isoforms of P450 efficiently produced active oxygen using electron spin resonance. Eight forms of P450 purified from rat liver were used.

Non-genomic modulation of dopamine release by bisphenol-A in PC12 cells.

An endocrine disruptor chemical, bisphenol-A (BPA), is reported to have several short-term actions in various tissues and/or cells; however, the mechanisms of these actions have not been fully elucidated. We investigated short-term actions evoked by BPA in pheochromocytoma PC12 cells. BPA elicited dopamine release in PC12 cells in a dose-dependent manner.

Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain.

mRNA of cytochrome P450 21-hydroxylase (P450c21) is expressed in the brain, but little is known about the enzymatic properties of P450c21 in the brain. In the present study, we showed, by using various recombinant cytochrome P450 (CYP)2D enzymes and anti-CYP2D4- or P450c21-specific antibodies, that rat brain microsomal steroid 21-hydroxylation is catalyzed not by P450c21, but by CYP2D isoforms. Rat CYP2D4 and human CYP2D6, which are the predominant CYP2D isoforms in the brain, possess 21-hydroxylation activity for both progesterone and 17alpha-hydroxyprogesterone.

NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation of hypoxia-inducible factor 1.

Hypoxia induces a group of physiologically important genes that include erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Hypoxia-inducible factor 1 (HIF-1) was identified as a hypoxia-activated transcription factor; however, the molecular mechanisms that underlie hypoxia signal transduction in mammalian cells remain undefined. In this study, we found that a flavoprotein, NADPH-P450 reductase (NPR), could regulate the induction of EPO mRNA under hypoxic conditions.