Identification of an aryl hydrocarbon receptor agonistic disperse dye in commercially available textile products by effect-directed analysis.

Textile products contain various chemicals, making safety evaluation complex. We conducted an exploratory investigation of aryl hydrocarbon receptor (AhR) agonists in textile products using effect-directed analysis (EDA), which combines biological assays and chemical analysis. A cell-based assay was employed to detect the activation of the AhR, using a cell line that expresses the AhR-responsive luciferase gene.

Epidermal Growth Factor Receptor Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage in Mice.

Background: Early brain injury including neuronal apoptosis is a main contributor to neurological deterioration after subarachnoid hemorrhage (SAH). This study was aimed to investigate whether EGFR (epidermal growth factor receptor)/NFκB (nuclear factor-kappa B) inducing kinase (NIK)/NFκB (p65 and p50) pathway is involved in the neuronal apoptosis after SAH in mice.

Methods: C57BL/6 adult male mice underwent endovascular perforation SAH modeling or sham-operation (n=286), and 86 mild SAH mice were excluded.

Development of a safer and improved analytical method for polycyclic aromatic hydrocarbons in creosote products.

Polycyclic aromatic hydrocarbons (PAHs) in creosote products used for wood preservation are regulated in Japan. Although the analytical method for this regulation has been stipulated by law, two main problems have been highlighted, namely the use of dichloromethane, a potential carcinogen, as a solvent and inadequate purification. Therefore, an analytical method to solve these problems was developed in this study.

Anti-Apoptotic Effects of AMPA Receptor Antagonist Perampanel in Early Brain Injury After Subarachnoid Hemorrhage in Mice.

This study was aimed to investigate if acute neuronal apoptosis is induced by activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptors (AMPARs) and inhibited by a clinically available selective AMPAR antagonist and antiepileptic drug perampanel (PER) in subarachnoid hemorrhage (SAH), and if the mechanisms include upregulation of an inflammation-related matricellular protein periostin. Sham-operated and endovascular perforation SAH mice randomly received an administration of 3 mg/kg PER or the vehicle intraperitoneally. Post-SAH neurological impairments and increased caspase-dependent neuronal apoptosis were associated with activation of AMPAR subunits GluA1 and GluA2, and upregulation of periostin and proinflammatory cytokines interleukins-1β and -6, all of which were suppressed by PER.

Clarithromycin Ameliorates Early Brain Injury After Subarachnoid Hemorrhage via Suppressing Periostin-Related Pathways in Mice.

Subarachnoid hemorrhage (SAH) remains a life-threatening disease, and early brain injury (EBI) is an important cause of poor outcomes. The authors have reported that periostin, a matricellular protein, is one of key factors of post-SAH EBI. Clarithromycin (CAM) is a worldwide antibiotic that can inhibit periostin expression.

[Analysis of Dieldrin and DTTB in Textiles].

Standard analytical methods for the detection of dieldrin and 4,6-dichloro-7-(2,4,5-trichlorophenoxy)-2-trifluoromethylbenzimidazole (DTTB) in textiles, which are regulated by Japanese law ("Act on the Control of Household Products Containing Harmful Substances"), have been in place for more than 30 years. In this study, we developed an improved analytical method, based on GC-MS, that uses safe reagents and can simultaneously detect dieldrin and DTTB analytes. In the standard (existing) analytical method, dimethyl sulfate, which is a potential carcinogen, is used to derivatize DTTB.

Morphological Characteristics of Neuronal Death After Experimental Subarachnoid Hemorrhage in Mice Using Double Immunoenzymatic Technique.

Subarachnoid hemorrhage (SAH) is a devastating disease. Neuronal death is an important pathophysiology in the acute phase of SAH, but the histopathological features of dying neurons have been poorly studied. Using several staining methods including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and microtubule-associated protein 2 (MAP-2) double immunolabeling, we investigated the morphological changes of nucleus and cytoskeleton in neurons and sought susceptible areas to neuronal death in filament perforation SAH mice under light microscope.

Toll-Like Receptor 4 and Tenascin-C Signaling in Cerebral Vasospasm and Brain Injuries After Subarachnoid Hemorrhage.

Toll-like receptor 4 (TLR4) is expressed in various cell types in the central nervous system and exerts maximal inflammatory responses among the TLR family members. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of a cerebral aneurysm, and therefore its activation is reasonable as an initial step of cascades to brain injuries after aneurysmal subarachnoid hemorrhage (SAH). TLR4 activation induces tenascin-C (TNC), a representative of matricellular proteins that are a class of inducible, nonstructural, secreted, and multifunctional extracellular matrix glycoproteins.

TAK-242, Toll-Like Receptor 4 Antagonist, Attenuates Brain Edema in Subarachnoid Hemorrhage Mice.

Background: Brain edema is a common and critical pathology following subarachnoid hemorrhage (SAH). Toll-like receptor 4 (TLR4) activation may exacerbate brain edema. The purpose of this study was to clarify if TAK-242, a TLR4 antagonist, suppresses brain edema formation and neurological impairments after SAH in mice.

The Role of Galectin-3 in Subarachnoid Hemorrhage: A Preliminary Study.

Despite advances in diagnosis and treatment of subarachnoid hemorrhage (SAH), combined morbidity and mortality rate in SAH patients accounted for greater than 50%. Many prognostic factors have been reported including delayed cerebral ischemia, cerebral vasospasm-induced infarction, and shunt-dependent hydrocephalus as potentially preventable or treatable causes. Recent experimental studies emphasize that early brain injury, a concept to explain acute pathophysiological events that occur in brain before onset of cerebral vasospasm within the first 72 h of SAH, may be more important than cerebral vasospasm, a classically important determinant of poor outcome, in post-SAH outcome.

Link Between Receptors That Engage in Developing Vasospasm After Subarachnoid Hemorrhage in Mice.

Vasospasm after subarachnoid hemorrhage (SAH) has been studied, but the mechanisms remain to be unveiled. Tenascin-C (TNC), which is a matricellular protein and reported to increase in spastic cerebral artery wall after SAH, is a ligand for both Toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR). Our previous studies suggested the involvement of TNC and these receptors in vasoconstriction or vasospasm after SAH.

Possible Involvement of Caspase-Independent Pathway in Neuronal Death After Subarachnoid Hemorrhage in Mice.

Early brain injury is now considered as an important cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage (SAH), and neuronal apoptosis is one of the constituents of early brain injury. Caspase family is popular proteases in apoptotic pathways, but there also exist caspase-independent cell death pathways in many pathologic states. In this study, we investigated the ratio of caspase-related and caspase-unrelated neuronal deaths in a mice endovascular perforation SAH model.

Machine Learning Analysis of Matricellular Proteins and Clinical Variables for Early Prediction of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Although delayed cerebral ischemia (DCI) is a well-known complication after subarachnoid hemorrhage (SAH), there are no reliable biomarkers to predict DCI development. Matricellular proteins (MCPs) have been reported relevant to DCI and expected to become biomarkers. As machine learning (ML) enables the classification of various input data and the result prediction, the aim of this study was to construct early prediction models of DCI development with clinical variables and MCPs using ML analyses.

Plasma Periostin and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (SAH). Matricellular protein periostin (POSTN) has been found to be upregulated and linked with early brain injury after experimental SAH. The aim of the present study was to investigate the relationship between plasma POSTN levels and various clinical factors including serum levels of C-reactive protein (CRP), an inflammatory marker, in 109 consecutive SAH patients whose POSTN levels were measured at days 1-12 after aneurysmal obliteration.

Anti-vasospastic Effects of Epidermal Growth Factor Receptor Inhibitors After Subarachnoid Hemorrhage in Mice.

Subarachnoid hemorrhage (SAH) is a devastating disease. Cerebral vasospasm is still an important cause of post-SAH poor outcomes, but its mechanisms remain unveiled. Activation of epidermal growth factor receptor (EGFR) is suggested to cause vasoconstriction in vitro, but no report has demonstrated the involvement of EGFR in vasospasm development after SAH in vivo.

Modified Citrus Pectin Prevents Blood-Brain Barrier Disruption in Mouse Subarachnoid Hemorrhage by Inhibiting Galectin-3.

Background and Purpose- Plasma levels of galectin-3-a matricellular protein-are increased after aneurysmal subarachnoid hemorrhage (SAH), but the functional significance remains undetermined. This study was conducted to evaluate whether modified citrus pectin (MCP; galectin-3 inhibitor) prevents post-SAH early brain injury, focusing on blood-brain barrier disruption. Methods- C57BL/6 male adult mice (n=251) underwent sham or filament perforation SAH modeling, followed by a random intracerebroventricular injection of vehicle or drug at 30 minutes post-modeling.

Tenascin-C in brain injuries and edema after subarachnoid hemorrhage: Findings from basic and clinical studies.

Subarachnoid hemorrhage (SAH) by a rupture of cerebral aneurysms remains the most devastating cerebrovascular disease. Early brain injury (EBI) is increasingly recognized to be the primary determinant for poor outcomes, and also considered to cause delayed cerebral ischemia (DCI) after SAH. Both clinical and experimental literatures emphasize the impact of global cerebral edema in EBI as negative prognostic and direct pathological factors.

Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.

There are no direct evidences showing the linkage between Toll-like receptor 4 (TLR4) and blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). The purpose of this study was to examine if selective blockage of TLR4 prevents BBB disruption after SAH in mice and if the TLR4 signaling involves mitogen-activated protein kinases (MAPKs). One hundred and fifty-one C57BL/6 male mice underwent sham or endovascular perforation SAH operation, randomly followed by an intracerebroventricular infusion of vehicle or two dosages (117 or 585 ng) of a selective TLR4 antagonist IAXO-102 at 30 min post-operation.