Bisecting GlcNAc modification of angiotensin-related glycoproteins in mouse kidney.

Structural variations of N-glycans critically regulate glycoprotein functions and are involved in various human diseases. N-Acetylglucosaminyltransferase-III (GnT-III or MGAT3) is highly expressed in the brain and kidney and is an N-glycan branching enzyme that biosynthesizes the unique N-glycan branch designated as bisecting GlcNAc. Its roles in Alzheimer's disease and cancer have been revealed, but the functions of bisecting GlcNAc in the kidney are poorly understood.

Novel function of transglutaminase 2 in extracellular histone-induced acute lung injury.

Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues.

Anti-seizure efficacy of perampanel in two established rodent models of early-life epilepsy.

Early-life seizures can be refractory to conventional antiseizure medications (ASMs) and can also result in chronic epilepsy and long-term behavioral and cognitive deficits. Treatments targeting age-specific mechanisms contributing to epilepsy would be of clinical benefit. One such target is the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subtype of excitatory glutamate receptor, which is upregulated in the developing brain.

Frequency of Immune Checkpoint Inhibitor-Induced Vasculitides: An Observational Study Using Data From the Japanese Adverse Drug Event Report Database.

Information on immune checkpoint inhibitor-induced vasculitides is limited, and predictors for this condition have not been identified. Therefore, we have examined the frequency of immune checkpoint inhibitor-induced vasculitides by analyzing the data recorded in the Japanese Adverse Drug Event Report database. Data from April 2004 to March 2020 were extracted, and vasculitides as an immune-related adverse event was defined according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

Concomitant Proton Pump Inhibitors and Immune Checkpoint Inhibitors Increase Nephritis Frequency.

Background/aim: Concomitant proton pump inhibitor (PPI) and immune checkpoint inhibitor (ICPI) were determined as risk factors of acute kidney injury. To identify the type of PPI associated with ICPI-induced nephritis, we used the Japanese Adverse Drug Event Report database.

Patients And Methods: ICPIs (nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab, and avelumab) and PPIs (esomeprazole, omeprazole, vonoprazan, rabeprazole, and lansoprazole) were selected as suspected nephritis-inducing drugs.

Detection and identification of potential transglutaminase 2 substrates in the mouse renal glomeruli.

The glomerulus primarily comprises mesangial cells, glomerular microvascular endothelial cells, and podocytes. IgA nephropathy is the most common primary glomerulonephritis worldwide and has a risk of progression to end-stage renal disease. IgA nephropathy is characterized by predominant IgA deposition in the glomerular mesangial area, where TG2 is significantly enhanced.

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism.

Cilostazol (CLZ), an anti-platelet agent, is primarily used following the onset of cerebral infarction. However, as CLZ is only marginally soluble in water, a strategy for patients with serious secondary conditions, such as impaired consciousness or aphagia, is required. In the present study, topical formulations containing CLZ nanocrystals (CLZ) were designed to enhance percutaneous absorption.

An oral formulation of cilostazol nanoparticles enhances intestinal drug absorption in rats.

Cilostazol (CLZ) is an anti-platelet agent that is generally used after the onset of cerebral infarction. However, CLZ is a poorly water-soluble drug and a strategy for increasing its bioavailability is required. In the present study, novel oral formulations were designed containing CLZ solid nanoparticles to improve bioavailability.

Diagnostic utility of automated SureFISH (Dako Omnis) in the diagnosis of musculoskeletal translocation-related sarcomas.

Fluorescence in situ hybridization (FISH) is an essential tool for genetic diagnosis in daily pathological work. Almost full automation of FISH can be achieved with the recently released automated SureFISH platform (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA). Its utility has been reported in HER2 amplification of breast and gastric carcinoma and ALK-rearranged lung cancer.

A Nanoparticle-Based Ophthalmic Formulation of Dexamethasone Enhances Corneal Permeability of the Drug and Prolongs Its Corneal Residence Time.

We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEX dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.

Co-administration of Magnesium Ion Prevents Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rats.

In a study to find ways to prevent the side effects of indomethacin (IMC), we previously reported that magnesium ion (Mg) can prevent the onset of IMC-induced gastric mucosa in adjuvant-induced arthritis (AA) rats, a model for rheumatoid arthritis (RA). In this study we investigated whether the co-administration of IMC and Mg prevents the formation and aggravation of intestinal ulcerogenic lesions in AA rats. The single oral administration of an excessive dose of IMC (40 mg/kg) induces hemorrhagic lesions and nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) in the jejunal and ileal mucosa of AA rats, and the extent of the lesions, as well as iNOS and NO levels in AA rats are higher than in normal rats.

[Improvement of Dissolution Rate and Stability in a Pirenoxine Ophthalmic Suspension by the Bead Mill Methods].

Foreign matter sensation and blurred vision following instillation of ophthalmic suspension are often observed, and remaining of solid particle on cornea is related these side effects. In addition, low dispersion stability in the ophthalmic suspension affects the therapeutic effect. In this study, we have attempted to enhance the dissolution rate and stability of commercially available pirenoxine ophthalmic suspension (CA-pirenoxine eye drops), anti-cataract eye drops, by changes in particle size.

Ferulic Acid Suppresses Amyloid Production in the Human Lens Epithelial Cell Stimulated with Hydrogen Peroxide.

It is well known that oxidative stresses induce the production of amyloid (A) in the brain, lens, and retina, leading to age-related diseases. In the present study, we investigated the effects of ferulic acid on the A levels in HO-stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of A peptides (A, A, and A) were measured by ELISA, and the levels of mRNA for the expressed proteins related to A production (APP, BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were determined by quantitative real-time RT-PCR.

Combination Ointment Containing Solid Tranilast Nanoparticles and Dissolved Sericin Is Efficacious for Treating Skin Wound-Healing Deficits and Redness in Diabetic Rats.

We attempted to design a combination ointment containing solid tranilast nanoparticles and dissolved sericin as a wound-healing drug (TS-combination ointment), and evaluated its usefulness as therapy for wound-healing deficits in streptozotocin-induced diabetic rat (STZ rat) using kinetic analyses as an index. Solid tranilast nanoparticles were prepared by bead mill methods with low-substituted methylcellulose; the mean particle size of the tranilast nanoparticles was 70 nm. The ointment was designed to contain the tranilast nanoparticles plus sericin powder and/or Carbopol 934.

A positive feedback loop between nitric oxide and amyloid β (1-42) accelerates mitochondrial damage in human lens epithelial cells.

We have reported that excessive nitric oxide (NO), like other reactive oxygen species (ROS), causes a decrease in cytochrome c oxidase (CCO) activity and ATP levels (mitochondrial damage) resulting in lens opacity. In addition, previous reports have shown that oxidative stress caused by ROS enhances amyloid β (Aβ) production in mammalian lenses, and that Aβ stimulates inducible nitric oxide synthase (iNOS) promoter activity. Based on these reports, we investigated the relationship between NO and Aβ production in human lens epithelial (HLE) cells.

Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles.

In the therapy of rheumatoid arthritis, ibuprofen (IBU) is widely used; however, it has been limited the clinical use by its systemic side effect, such as gastrointestinal lesions. Therefore, we prepared topical gel ointment used IBU solid nanoparticles (IBU-gel formulation). In addition, we demonstrated their anti-inflammatory effect by using arthritis model rat (adjuvant-induced arthritis rat, AA rat).

An Ophthalmic Formulation of Disulfiram Nanoparticles Prolongs Drug Residence Time in Lens.

Disulfiram (DSF) is a dimer of diethyldithiocarbamate (DDC) that we previously added to a solution of 2-hydroxypropyl-β-cyclodextrin (DSF solution). We found that the instillation of this DSF solution delayed lens opacification in a hereditary cataractous ICR/f rat. In this study, we attempted to design an ophthalmic formulation containing DSF nanoparticles for use as a lens targeted drug delivery system (nano-DSF suspension), and investigated the changes in drug content in the lens after the instillation of DSF solution or nano-DSF suspension.

Size effect of rebamipide ophthalmic nanodispersions on its therapeutic efficacy for corneal wound healing.

In a variety of tissues including gastrointestinal mucosa, rebamipide (REB) provides cytoprotection, prevents inflammation, and promotes wound healing. Clinically, REB ophthalmic dispersions are used to treat diabetic keratopathy. In this study, we investigated the optimal particle size of REB to promote corneal wound healing using a model of diabetic keratopathy, the debrided corneal epithelium from Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Hyperglycemia Enhances the Production of Amyloid β1-42 in the Lenses of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes.

Purpose: It has been reported that the accumulation of amyloid β1-42 (Aβ1-42) in human lenses can cause some forms of lens opacification. However, the factors leading to changes in the accumulation of Aβ in the lens remain obscure. In this study, we investigate the effect of hyperglycemia on Aβ1-42 accumulation in lenses.

Increased Expression of Interleukin-18 in Lenses of Ovariectomized Rats.

Previous studies showed an increased prevalence of cataracts in postmenopausal women. In this study, we investigated changes in the levels of calcium ion (Ca(2+)) and interleukin (IL)-18, which are factors in cataract development, in the lenses of ovariectomized (OVX) rats, a model of postmenopausal woman. Although the Ca(2+) content in the blood of OVX rats increased 1 month after ovariectomy and subsequently decreased, the Ca(2+) content in the lenses was unchanged in OVX rats 1-3 months after ovariectomy.

Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model.

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.

Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles.

We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KETnano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KETnano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm.

Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat.

It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h.

Lipase member H frequently overexpressed in human esophageal adenocarcinomas.

Esophageal cancer is one of the most frequent causes of cancer-related deaths worldwide. This is due to its asymptomatic nature or mild nonspecific symptoms. Most patients are diagnosed after appearance of prominent symptoms, and tumors are frequently accompanied by severe infiltration.