In vitro treatment with liposome-encapsulated Mannose-1-phosphate restores N-glycosylation in PMM2-CDG patient-derived fibroblasts.

PMM2-CDG is the most common congenital disorder of glycosylation (CDG). Patients with this disease often carry compound heterozygous mutations of the gene encoding the phosphomannomutase 2 (PMM2) enzyme. PMM2 converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P), which is a critical upstream metabolite for proper protein N-glycosylation.

Elevated Serum Xanthine Oxidase and Its Correlation with Antioxidant Status in Patients with Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged.

Thoracic Intra and Extramedullary Capillary Hemangioma with Subacute Clinical Course: A Case Report and Literature Review.

Capillary hemangiomas are benign tumors comprising a lobulated proliferation of capillary vessels frequently located in the soft tissues of the neck and head. Spinal intradural capillary hemangiomas are rare, particularly intramedullary lesions. To our knowledge, only 31 cases of spinal intramedullary capillary hemangiomas have been reported.

High Tumoral STMN1 Expression Is Associated with Malignant Potential and Poor Prognosis in Patients with Neuroblastoma.

Background: Stathmin 1 (STMN1), a marker for immature neurons and tumors, controls microtubule dynamics by destabilizing tubulin. It plays an essential role in cancer progression and indicates poor prognosis in several cancers. This potential protein has not been clarified in clinical patients with neuroblastoma.

Analysis of clinicopathological features and NAB2-STAT6 fusion variants of meningeal solitary fibrous tumor with ectopic salivary gland components in the cerebellopontine angle.

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood.

Efficacy and safety of oral sulfate solution for bowel preparation in Japanese patients undergoing colonoscopy: Noninferiority-based, randomized, controlled study.

Objectives: To compare the efficacy and safety of oral sulfate solution administered using the same-day dose and the split-dose regimens with those of polyethylene glycol plus ascorbate solution, used for bowel preparation in Japanese patients undergoing colonoscopy.

Methods: This multicenter (n = 13), randomized, active-controlled, colonoscopist- and image evaluator-blinded, noninferiority study with parallel-group comparison recruited 632 patients from December 2018 to June 2019. Of these, 602 patients were divided into the oral sulfate solution same-day dose group (n = 200); oral sulfate solution split-dose group (n = 202); and polyethylene glycol plus ascorbate same-day dose group (n = 200).

Xanthine oxidase inhibition attenuates insulin resistance and diet-induced steatohepatitis in mice.

Hyperuricemia drives the development of nonalcoholic fatty liver disease (NAFLD). Pharmacological inhibition of xanthine oxidase (XO), a rate-limiting enzyme for uric acid (UA) production, has been demonstrated to improve hepatic steatosis in diet-induced obese mice. However, it remains unclear whether inhibition of XO improves nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, in terms of both liver inflammation and fibrosis.

Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study.

Aims/introduction: There is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally- and systemically-activated xanthine oxidase (XO), a rate-limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents.

Febuxostat ameliorates secondary progressive experimental autoimmune encephalomyelitis by restoring mitochondrial energy production in a GOT2-dependent manner.

Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE.

Matrix Density Engineering of Hydrogel Nanoparticles with Simulation-Guided Synthesis for Tuning Drug Release and Cellular Uptake.

The use of a nanoparticle (NP)-based antitumor drug carrier has been an emerging strategy for selectively delivering the drugs to the tumor area and, thus, reducing the side effects that are associated with a high systemic dose of antitumor drugs. Precise control of drug loading and release is critical so as to maximize the therapeutic index of the NPs. Here, we propose a simple method of synthesizing NPs with tunable drug release while maintaining their loading ability, by varying the polymer matrix density of amine- or carboxyl-functionalized hydrogel NPs.

Analysis of Staphylococcal Toxins and Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia.

It is well known that methicillin-resistant Staphylococcus aureus (MRSA) produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The aim of study was to identify staphylococcal pathogenicity that may affect the prognosis of patients with MRSA bacteremia. We obtained 149 MRSA strains from blood cultures between January 2009 and December 2014 in our institution.

Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.

Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial.

More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia.

Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan).

Changes in the Distribution of Capsular Serotypes of Streptococcus pneumoniae Isolated from Adult Respiratory Specimens in Japan.

Objective: The objective of this study was to assess whether the distribution of pneumococcal capsular types has been changed, while also providing basic data on changes in the distribution after the introduction of Pneumococcal conjugated vaccine (PCV)13 in adult medical practice.

Methods: We analyzed 431 Streptococcus pneumoniae strains (200 in 2006 and 231 in 2012) that had been isolated from respiratory infection specimens from adult patients. Capsular typing was performed by the Quellung reaction and multiplex polymerase chain reaction.

Hydrogel Nanoparticles with Thermally Controlled Drug Release.

Improving the therapeutic efficacy and reducing systemic side effects of drugs is an important aspect in chemotherapy. The strategy presented here is the use of cisplatin loaded, temperature-sensitive, hydrogel nanoparticles (CisPt-NPs) and their ability to deliver and release chemodrugs selectively, based on thermal stimuli. The specially synthesized CisPt-NPs show a temperature-dependent increase of cisplatin release, at neutral pH (as in blood and normal tissue), in both the presence and absence of common metallic ions, as well as at the low pH found in lysosomes, where endocytosed NPs often localize.

Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis in mice.

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear.

A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H.

[A case of cysticercosis with multiple lesions in the brain and femoral muscles].

A 37-year-old Nepalese man was admitted to Showa University Hospital because of a loss of consciousness and seizures. He had lived in Nepal, Qatar, Singapore, and India before the age of 34 years. He had no history of having eaten raw pork.

Xanthine oxidase mediates axonal and myelin loss in a murine model of multiple sclerosis.

Objectives: Oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS). Though reactive oxygen species (ROS) are produced by various mechanisms, xanthine oxidase (XO) is a major enzyme generating ROS in the context of inflammation. The objectives of this study were to investigate the involvement of XO in the pathogenesis of MS and to develop a potent new therapy for MS based on the inhibition of ROS.

Uric acid secretion from adipose tissue and its increase in obesity.

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity.