Insights Into the Inhibition of MOX-1 β-Lactamase by S02030, a Boronic Acid Transition State Inhibitor.

The rise of multidrug resistant (MDR) Gram-negative bacteria has accelerated the development of novel inhibitors of class A and C β-lactamases. Presently, the search for novel compounds with new mechanisms of action is a clinical and scientific priority. To this end, we determined the 2.

Uniformity and Efficacy of Dry Powders Delivered to the Lungs of a Mycobacterial-Surrogate Rat Model of Tuberculosis.

Purpose: Pulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than systemic medication. However, in the pre-clinical study phase, there is a lack of devices for effective delivery of dry powders to the lungs of small rodents. In this study, an administration device which utilizes Venturi effect to deliver dry powders to the lungs homogeneously was developed.

Sitafloxacin reduces tumor necrosis factor alpha (TNFα) converting enzyme (TACE) phosphorylation and activity to inhibit TNFα release from lipopolysaccharide-stimulated THP-1 cells.

Sepsis is a systemic reaction to an infection and resulting in excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study aimed to identify quinolone antibiotics that can reduce tumor necrosis factor alpha (TNFα) production and to elucidate mechanisms underlying inhibition of TNFα production.

Genes for tRNA recycling are upregulated in response to infection with Theiler's mouse encephalitis virus.

The concept of tRNA recycling has recently emerged from the studies of ribosome-associated quality control. Therein tRNase Z removes the 2', 3'>p from the ANKZF1-cleaved tRNA and the subsequent TRNT1 action re-generates the intact tRNA. To know the roles of the tRNA recycling in vivo, we investigated how viral infection affects the tRNA recycling system by analyzing the mRNA levels of tRNase Z and TRNT1.

Endothelial-specific depletion of TGF-β signaling affects lymphatic function.

Background: Transforming growth factor (TGF)-β is a multifunctional cytokine involved in cell differentiation, cell proliferation, and tissue homeostasis. Although TGF-β signaling is essential for maintaining blood vessel functions, little is known about the role of TGF-β in lymphatic homeostasis.

Methods: To delineate the role of TGF-β signaling in lymphatic vessels, TβRII mice were crossed with Prox1-Cre mice to generate TβRII; Prox1-Cre mice.

Fungal Planet description sheets: 1284-1382.

Novel species of fungi described in this study include those from various countries as follows: , from coastal sea sand. , on soil, on dead wood, from roots and leaves of and from capsules of , (incl. gen.

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice.

Elimination of senescent cells (senolysis) was recently reported to improve normal and pathological changes associated with aging in mice. However, most senolytic agents inhibit antiapoptotic pathways, raising the possibility of off-target effects in normal tissues. Identification of alternative senolytic approaches is therefore warranted.

Perturbing the Normal Level of SIDT1 Suppresses the Naked ASO Effect.

Although antisense oligonucleotide (ASO) therapeutics can be taken up by living cells without carrier molecules, a large part of incorporated ASOs are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism of cellular uptake and intracellular trafficking of ASOs. In this study, we investigated how SIDT1 affects cellular uptake and intracellular trafficking of ASOs.

Risk of Pregabalin-Induced Hypoglycemia: Analysis of the Japanese Adverse Drug Event Report Database.

Pregabalin is a first-line treatment option for neuropathic pain. Recently, some cases of pregabalin-induced hypoglycemia have been reported, which can complicate the treatment of neuropathic pain and worsen patient outcomes. Therefore, a better understanding of the clinical condition of patients with pregabalin-induced hypoglycemia is desirable.

Transcription from the proximal promoter of ELAC1, a gene for tRNA repair, is upregulated by interferons.

tRNase Z (ELAC1) and TRNT1 function in tRNA recycling. Recently, we have shown that these genes are upregulated in the cells infected with Theiler's mouse encephalitis virus (TMEV), implying that tRNA recycling functions in response to viral infection. To address the molecular mechanism underlying the ELAC1 upregulation in the cells infected with TMEV, we performed luciferase assays using various plasmid constructs harboring the ELAC1 promoter region.

Pharmacist involved education program in a multidisciplinary team for oral mucositis: Its impact in head-and-neck cancer patients.

Objectives: This retrospective study examined how a pharmacist-involved education program in a multidisciplinary team (PEMT) for oral mucositis (OM) affected head-and-neck cancer (HNC) patients receiving concurrent chemoradiotherapy (CCRT).

Materials And Methods: Total samples data of 53 patients during the stipulated timeframe were retrospectively collected from electronic medical records from February 2017 to January 2019. We compared the presence/absence of OM (OM: yes/no) between patients with and without PEMT (PEMT: yes/no) as the primary endpoint and OM severity as the secondary endpoint.

Space Exposure of Amino Acids and Their Precursors during the Tanpopo Mission.

Amino acids have been detected in extraterrestrial bodies such as carbonaceous chondrites (CCs), which suggests that extraterrestrial organics could be the source of the first life on Earth, and interplanetary dust particles (IDPs) or micrometeorites (MMs) are promising carriers of extraterrestrial organic carbon. Some amino acids found in CCs are amino acid precursors, but these have not been well characterized. The Tanpopo mission was conducted in Earth orbit from 2015 to 2019, and the stability of glycine (Gly), hydantoin (Hyd), isovaline (Ival), 5-ethyl-5-methylhydantoin (EMHyd), and complex organics formed by proton irradiation from CO, NH, and HO (CAW) in space were analyzed by high-performance liquid chromatography and/or gas chromatography/mass spectrometry.

Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat.

Background: The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP.

Suppression of Tumor Growth in a Rabbit Hepatic Cancer Model by Boron Neutron Capture Therapy With Liposomal Boron Delivery Systems.

Background/aim: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between B and thermal neutrons. The accumulation of B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation.

Two-Body Metastable Dissociation of -Pentane and -Hexane Triplet Dications in Intense Femtosecond-Laser Fields.

Mass spectra of -pentane and -hexane ionized through femtosecond-laser pulses were measured using a time-of-flight mass spectrometer. Fragment ions ejected with large kinetic energies were identified as side peaks in which a two-body dissociation pathway, CH → CH + CH, was identified for -pentane, and two for -hexane, CH → CH + CH and CH + CH, based on momentum matching of the fragments. The two-body dissociation pathways were observed when the polarization direction of the linearly polarized laser light was perpendicular to the molecular axis.

Manganese toxicity disrupts indole acetic acid homeostasis and suppresses the CO assimilation reaction in rice leaves.

Despite the essentiality of Mn in terrestrial plants, its excessive accumulation in plant tissues can cause growth defects, known as Mn toxicity. Mn toxicity can be classified into apoplastic and symplastic types depending on its onset. Symplastic Mn toxicity is hypothesised to be more critical for growth defects.

Low-Protein Diet: History and Use of Processed Low-Protein Rice for the Treatment of Chronic Kidney Disease.

The epidemiology of chronic kidney disease (CKD) shows increasing trends in prevalence and mortality and has become the leading health problem worldwide. Reducing the amount of proteins ingested from rice is an easy way to control the total intake of proteins, saving energy sources, particularly in rice-eating countries. In Japan, low-protein white rice had been developed, but the taste and function were not satisfactory for CKD patients.

Genomic and Metabolomic Analyses of a Piezosensitive Mutant of and Application for Generation of Piezosensitive Niigata- Yeast Strains.

A sparkling-type draft cloudy (Japanese rice wine), AWANAMA, was recently developed using high hydrostatic pressure (HHP) treatment as a non-thermal pasteurization method. This prototype has a high potential market value, since it retains the fresh taste and flavor similar to draft while avoiding over-fermentation. From an economic point of view, a lower pressure level for HHP pasteurization is still required.

The impact that family members' health care experiences have on patients' trust in physicians.

Background: A family member's negative experiences with medical care have long-term effects on a patient's attitudes and emotions. However, the impact of family members' experiences on patients' trust in their own physicians and in physicians generally is poorly understood. This study aims to quantify these associations.

Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells.

The aim of this study was to identify genes that are specifically expressed in pancreatic islet β-cells (hereafter referred to as β-cells). Large-scale complementary DNA-sequencing analysis was performed for 3,429 expressed sequence tags derived from murine MIN6 β-cells, through homology comparisons using the GenBank database. Three individual ESTs were found to code for protease serine S1 family member 53 ().

Altered microbiota by a high-fat diet accelerates lethal myeloid hematopoiesis associated with systemic SOCS3 deficiency.

The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined.

p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis.

Background: The neuronal ceroid lipofuscinosis (NCL) are a group of autosomal recessive neurodegenerative disorders that are characterized by the accumulation of ceroid lipofuscins. The NCLs are categorized into four classes based on the age of onset. Kufs disease is a rare adult-onset NCL caused by mutations in the CLN6 gene, which is rarely observed in the Japanese population.