Discovery of a cystathionine γ-lyase (CSE) selective inhibitor targeting active-site pyridoxal 5'-phosphate (PLP) via Schiff base formation.

D,L-Propargylglycine (PAG) has been widely used as a selective inhibitor to investigate the biological functions of cystathionine γ-lyase (CSE), which catalyzes the formation of reactive sulfur species (RSS). However, PAG also inhibits other PLP (pyridoxal-5'-phosphate)-dependent enzymes such as methionine γ-lyase (MGL) and L-alanine transaminase (ALT), so highly selective CSE inhibitors are still required. Here, we performed high-throughput screening (HTS) of a large chemical library and identified oxamic hydrazide 1 as a potent inhibitor of CSE (IC = 13 ± 1 μM (mean ± S.

[Stenotic ischemic enteritis secondary to intraperitoneal band infiltration: a case report].

A 55-year-old man presented with vomiting and upper abdominal pain. Two months later, computed tomography revealed jejunal wall thickening and contrast enhancement. Double-balloon endoscopy revealed severe jejunal stenosis and mucosal prolapse.

Colorectal Cancer Patients Have Four Specific Bacterial Species in Oral and Gut Microbiota in Common-A Metagenomic Comparison with Healthy Subjects.

Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Use of the Multilayer Fragment Molecular Orbital Method to Predict the Rank Order of Protein-Ligand Binding Affinities: A Case Study Using Tankyrase 2 Inhibitors.

In computational drug discovery, ranking a series of compound analogues in the order that is consistent with the experimental binding affinities remains a challenge. Many of the computational methods available for evaluating binding affinities have adopted molecular mechanics (MM)-based force fields, although they cannot completely describe protein-ligand interactions. By contrast, quantum mechanics (QM) calculations play an important role in understanding the protein-ligand interactions; however, their huge computational costs hinder their application in drug discovery.

Theoretical study on photo-induced processes of 1-methyl-3-(N-(1,8-naphthalimidyl)ethyl)imidazolium halide species: an application of constrained density functional theory.

1-Methyl-3-(N-(1,8-naphthalimidyl)ethyl)imidazolium (MNEI) has potential as a versatile sensor that can measure the electronegativity of anions based on the fluorescence intensity upon irradiation. To clarify the factors that determine the fluorescence intensity, constrained density functional theory (CDFT) was applied to explore the electron transfer (ET) states of MNEI halide species (MNEI-X; X = F, Cl, Br, I). According to the CDFT potential energy surface, intra-molecular ET (S) states on MNEI are responsible for the intensity of absorption and fluorescence spectra.

BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.

Methods: The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue.

Expression of glucose transporter-1 is correlated with hypoxia-inducible factor 1α and malignant potential in pancreatic neuroendocrine tumors.

The present study aimed to investigate the prognostic usefulness of the expression of glucose transporter type 1 (GLUT-1) and GLUT-2, hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor II messenger RNA-binding protein 3 (IMP3) in pancreatic neuroendocrine tumors (pNETs). Immunohistochemical staining for GLUT-1, GLUT-2, HIF-1α and IMP3 was performed in 70 pNET specimens. The expression of GLUT-1 and HIF-1α was significantly higher in the World Health Organization grade 2 (G2), neuroendocrine carcinoma cases and mixed-type pNETs compared with the G1 cases.

Intermolecular electron transfer states of 1-methyl-3-(N-(1,8-naphthalimidyl)ethyl)imidazolium iodide obtained by constrained density functional theory.

Electron transfer (ET) states of 1-methyl-3-(N-(1,8-naphthalimidyl)ethyl)imidazolium iodide are responsible for its photophysics. Investigation of an ET state based on constrained density functional theory (CDFT) revealed that nonradiative decay from the ET excited state is mediated by the interaction of the iodine atom with the 1,8-naphthalimide or the imidazolium group.

Assessment and acceleration of binding energy calculations for protein-ligand complexes by the fragment molecular orbital method.

In the field of drug discovery, it is important to accurately predict the binding affinities between target proteins and drug applicant molecules. Many of the computational methods available for evaluating binding affinities have adopted molecular mechanics-based force fields, although they cannot fully describe protein-ligand interactions. A noteworthy computational method in development involves large-scale electronic structure calculations.

Metabolic Profiling of Developing Pear Fruits Reveals Dynamic Variation in Primary and Secondary Metabolites, Including Plant Hormones.

Metabolites in the fruits of edible plants include sweet sugars, visually appealing pigments, various products with human nutritional value, and biologically active plant hormones. Although quantities of these metabolites vary during fruit development and ripening because of cell division and enlargement, there are few reports describing the actual dynamics of these changes. Therefore, we applied multiple metabolomic techniques to identify the changes in metabolite levels during the development and ripening of pear fruits (Pyrus communis L.

Trimer effects in fragment molecular orbital-linear combination of molecular orbitals calculation of one-electron orbitals for biomolecules.

The fragment molecular orbital (FMO)-linear combination of molecular orbitals (LCMO) method incorporates as an efficient post-process calculation of one-electron orbitals of the whole system after the FMO total energy calculation. A straightforward way to increase the accuracy is inclusion of the trimer effect. Here, we derive a comprehensive formulation called the FMO3-LCMO method.

MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis.

Background: MicroRNAs (miRNAs) have been gaining attention as new, key molecules that contribute to carcinogenesis. In pancreatic cancer, previous profiling analyses of miRNA expression have shown that several miRNAs are differently expressed in normal and cancerous tissues. Several pancreatic cancer-specific miRNAs differed, however, in each analysis.

Effects of freeze-drying of samples on metabolite levels in metabolome analyses.

Freeze-drying (FD) is a useful technique for removing water from biological tissues, such as food samples. Cellular components freeze at once, and the ice sublimates under conditions of high vacuum and low temperatures. Because biological activity is restricted during FD, the degradation of cellular metabolites is often believed to be limited.

Classification of cerebellar atrophy using voxel-based morphometry and SPECT with an easy Z-score imaging system.

Objective: With conventional MRI and single-photon emission computed tomography (SPECT), accurate diagnosis and precise classification of cerebellar atrophy are often difficult. The objective was to verify the utility of MRI voxel-based morphometry (VBM) in combination with SPECT using easy Z-score imaging (eZIS) for diagnosing and classifying cerebellar atrophy.

Patients And Methods: We assessed gray matter atrophy using VBM and blood perfusion using SPECT with eZIS in fifteen patients with different types of cerebellar atrophy, such as the cerebellar variant of multiple system atrophy (MSA-C), spinocerebellar ataxia type 3 (SCA3), SCA6, and autoimmune cerebellar ataxia (AICA).

Carcinoembryonic antigen-related cell adhesion molecule 1 modulates experimental autoimmune encephalomyelitis via an iNKT cell-dependent mechanism.

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a CEA family member that has been reported to have an important role in the regulation of Th1-mediated colitis. In this study, we examined the role of CEACAM1 in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Treatment of C57BL/6J mice with CEACAM1-Fc fusion protein, a homophilic ligand of CEACAM1, inhibited the severity of EAE and reduced myelin oligodendrocyte glycoprotein-derived peptide (MOG(35-55))-reactive interferon-gamma and interleukin-17 production.

Efficacy of major hepatectomy for large hepatocellular carcinoma.

Background/aims: Large hepatocellular carcinomas (HCC) with diameter >10 cm reportedly displays poor prognosis. The role of hepatic resection in the treatment of large HCC remains controversial. We evaluated the efficacy of hepatic resection, particularly major hepatectomy, for large HCC.

Intravenous immunoglobulin therapy for autoantibody-positive cerebellar ataxia.

Objective: It has been reported that autoimmune cerebellar ataxias, such as anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia and gluten ataxia, are treatable. Here, we examined the therapeutic efficacy of intravenous immunoglobulin (IVIg) on autoantibody-positive cerebellar ataxia.

Patients And Methods: IVIg therapy was administered in seven autoantibody-positive cerebellar ataxia patients.

[A case of anti-gliadin-antibody-positive cerebellar ataxia effectively treated with intravenous immunoglobulin in which voxel-based morphometry and FineSRT were diagnostically useful].

We present the case of a 51-year-old man with a 5-year history of slowly progressive gait ataxia and dysarthria who showed a wide-based gait requiring assistance. The patient's score on the Revised Hasegawa Dementia Scale (HDS-R) was 22/30 and constructional apraxia was also evident. Cerebrospinal fluid analysis showed 3 cells/microl, and the protein concentration was 58 mg/dl.

Description of core excitations by time-dependent density functional theory with local density approximation, generalized gradient approximation, meta-generalized gradient approximation, and hybrid functionals.

Time-dependent density functional theory (TDDFT) is employed to investigate exchange-correlation-functional dependence of the vertical core-excitation energies of several molecules including H, C, N, O, and F atoms. For the local density approximation (LDA), generalized gradient approximation (GGA), and meta-GGA, the calculated X1s-->pi* excitation energies (X = C, N, O, and F) are severely underestimated by more than 13 eV. On the other hand, time-dependent Hartree-Fock (TDHF) overestimates the excitation energies by more than 6 eV.

Wavelet transform analysis of ab initio molecular dynamics simulation: application to core-excitation dynamics of BF3.

We propose a novel analysis method of ab initio molecular dynamics (AIMD) simulation using a continuous wavelet transform (c-WT) technique. The c-WT technique, one of the time-frequency signal analysis methods, provides a clear view of the dynamical information in time developments. Combined with the auto-correlation function of velocity by AIMD simulation, c-WT analysis enables us to well understand dynamical distribution, such as the vibrational properties following a change of electronic structure in a molecular system.

Time-dependent density functional theory calculations for core-excited states: assessment of standard exchange-correlation functionals and development of a novel hybrid functional.

A new hybrid functional for accurate descriptions of core and valence excitations, the core-valence Becke's three-parameter exchange (B3)+Lee-Yang-Paar (LYP) correlation functional (CV-B3LYP), is proposed. The construction of the new hybrid functional is based on the assessment that B3LYP performs well for properties concerning valence electrons and Becke's half-and-half exchange+LYP functional (BHHLYP), which includes 50% portion of Hartree-Fock exchange, performs well for core excitations. By using the appropriate portions of Hartree-Fock exchange for core and valence regions separately, CV-B3LYP overcomes the disadvantages of BHHLYP and B3LYP, which give inferior descriptions of valence and core excitations, respectively.