Preparation of natural high-mannose-type oligosaccharides (GlcManGlcNAc) with the asparagine-glycine-threonine as consensus sequence from chicken egg yolk.

High-mannose-type glycan structure of N-glycoproteins plays important roles in the proper folding of proteins in sorting glycoprotein secretion and degradation of misfolded proteins in the endoplasmic reticulum (ER). The GlcManGlcNAc (G1M9)-type N-glycan is one of the most important signaling molecules in the ER. However, current chemical synthesis strategies are laborious, warranting more practical approaches for G1M9-glycopeptide development.

In vitro demetalation of central magnesium in various chlorophyll derivatives using Mg-dechelatase homolog from the chloroflexi Anaerolineae.

In the metabolic pathway of chlorophylls (Chls), an enzyme called STAY-GREEN or SGR catalyzes the removal of the central magnesium ion of Chls and their derivatives to their corresponding free bases, including pheophytins. The substrate specificity of SGR has been investigated through in vitro reactions using Chl-related molecules. However, information about the biochemical properties and reaction mechanisms of SGR and its substrate specificity remains elusive.

Predicted Structure of the BciC Enzyme Catalyzing the Removal of the C13-Methoxycarbonyl Group for Biosynthesis of Chlorosomal Chlorophylls: A Mechanism for Dual Catalytic Functions of Hydrolysis and Decarboxylation inside Its Active Site.

Green photosynthetic bacteria, one of the phototrophs, have the largest and most efficient light-harvesting antenna systems, called chlorosomes. The core part of chlorosomes consists of unique bacteriochlorophyll // molecules. In the biosynthetic pathway of these molecules, a BciC enzyme catalyzes the removal of the C13-methoxycarbonyl group of chlorophyllide .

In vitro reversible dehydration in C3-substituents of zinc chlorophyll analogs by BchF and BchV enzymes: Stereoselectivity and substrate specificity in the dehydration.

In the biosynthetic pathway of bacteriochlorophyll(BChl)-a/b/c/d/e molecules, BchF and BchV enzymes catalyze the hydration of a C3-vinyl to C3-1-hydroxyethyl group. In this study, the in vitro reactions catalyzed by BchF and BchV partially afforded a C3-epimeric mixture of the hydrated products (secondary alcohols), with the primary recovery of the C3-vinylated substrate. The stereoselectivity and substrate specificity for the in vitro reverse enzymatic dehydration were examined using zinc chlorophyll analogs as model substrates by BchF and BchV, which were obtained from extracts of Escherichia coli overexpressing the respective genes from Chlorobaculum tepidum and used without further purification.

Chiral-phase HPLC separation of (divinyl-)protochlorophyllide-a enantiomers as key precursors in chlorophyll biosynthesis from their 13-stereoisomeric prime forms.

Protochlorophyllide(PChlide)-a and its 8-vinylated analog, divinyl(DV)-PChlide-a, are common and essential intermediates in the biosynthesis of all naturally occurring chlorophyll (Chl) pigments. These porphyrinoid-type pigments have a single optically active (asymmetric) carbon atom at the 13-position, so their stereoisomers are (13R)- and (13S)-enantiomers. The former and latter are called (DV-)PChlide-a and (DV-)PChlide-a', respectively.

Characterization of regioisomeric diterpenoid tails in bacteriochlorophylls produced by geranylgeranyl reductase from Halorhodospira halochloris and Blastochloris viridis.

Geranylgeranyl reductase (GGR) encoded by the bchP gene catalyzes the reductions of three unsaturated C = C double bonds (C6 = C7, C10 = C11, and C14 = C15) in a geranylgeranyl (GG) group of the esterifying moiety in 17-propionate residue of bacteriochlorophyll (BChl) molecules. It was recently reported that GGR in Halorhodospira halochloris potentially catalyzes two hydrogenations, yielding BChl with a tetrahydrogeranylgeranyl (THGG) tail. Furthermore, its engineered GGR, in which N-terminal insertion peptides characteristic for H.

Effect of early nutritional initiation on post-cerebral infarction discharge destination: A propensity-matched analysis using machine learning.

Aim: Malnutrition is associated with poor outcomes in cerebral infarction patients, with research indicating that early nutritional initiation may improve the short-term prognosis of patients. However, evidence supported by big data is lacking. Here, to determine the effect of nutritional initiation during the first 3 days after hospital admission on home discharge rates, propensity score matching was conducted in patients with acute cerebral infarction.

Enhanced G1 arrest and apoptosis via MDM4/MDM2 double knockdown and MEK inhibition in wild-type colon and gastric cancer cells with aberrant KRAS signaling.

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin-ligase activity. MDM4 cooperates with MDM2-mediated p53 degradation, directly inhibiting p53 transcription by binding to its transactivation domain. Our previous study reported that the simultaneous inhibition of MDM2 and MDM4 using nutlin-3 (an inhibitor of the MDM2-p53 interaction) and chimeric small interfering RNA with DNA-substituted seed arms (named chiMDM2 and chiMDM4) more potently activated p53 than the MDM2 or MDM4 inhibitor alone and synergistically augmented antitumor effects in various types of cancer cells with the wild-type (wt) .

MDM4 as a Prognostic Factor for Patients With Gastric Cancer With Low Expression of p53.

Background/aim: The oncoproteins murine double minute (MDM) 2 and MDM4 inactivate tumor-suppressor protein p53. Their mutual relationship with the prognosis of gastric cancer (GC) remains unknown.

Patients And Methods: Expression of MDM2, MDM4, and p53 in tumors of 241 patients with GC were evaluated immunohistochemically.

Detection of 13-carboxy-chlorin produced by the in vitro BciC enzymatic hydrolysis of zinc chlorophyllide.

Green photosynthetic bacteria with an efficient light-harvesting system contain special chlorophyll molecules, called bacteriochlorophylls c, d, e, in their main antennae. In the biosynthetic pathway, a BciC enzyme is proposed to catalyze the hydrolysis of the C13-methoxycarbonyl group of chlorophyllide a, but the resulting C13-carboxy group has not been detected yet because it is spontaneously removed due to the instability of the β-keto-carboxylic acid. In this study, the in vitro BciC enzymatic reactions of zinc methyl (13R/S)-hydroxy-mesochlorophyllides a were examined and a carboxylic acid possessing the C13S-OH was first observed as the hydrolyzed product of the C13-COOCH.

In Vitro Hydrolysis of Zinc Chlorophyllide Homologues by a BciC Enzyme.

Chlorosomes in green photosynthetic bacteria are the largest and most efficient light-harvesting antenna systems of all phototrophs. The core part of chlorosomes consists of bacteriochlorophyll , , or molecules. In their biosynthetic pathway, a BciC enzyme catalyzes the removal of the C13-methoxycarbonyl group of chlorophyllide .

In vitro C13-dealkoxycarbonylations of zinc chlorophyll a derivatives including C13-substitutes by a BciC enzyme.

Chlorosomes in the green photosynthetic bacteria are the largest and most efficient light-harvesting antenna systems of all phototrophs. The core part of chlorosomes consists of bacteriochlorophyll c, d, e, or f molecules. In their biosynthetic pathway, a BciC enzyme catalyzes the removal of the C13-methoxycarbonyl group of chlorophyllide a.

BciC-Catalyzed C13 -Demethoxycarbonylation of Metal Pheophorbide a Alkyl Esters.

Bacteriochlorophyll c molecules self-aggregate to form large oligomers in the core part of chlorosomes, which are the main light-harvesting antenna systems of green photosynthetic bacteria. In the biosynthetic pathway of bacteriochlorophyll c, a BciC enzyme catalyzes the removal of the C13 -methoxycarbonyl group of chlorophyllide a, which possesses a free propionate residue at the C17-position and a magnesium ion as the central metal. The in vitro C13 -demethoxycarbonylations of chlorophyll a derivatives with various alkyl propionate residues and central metals were examined by using the BciC enzyme derived from one green sulfur bacteria species, Chlorobaculum tepidum.

Synthesis of chlorophyll-a homologs by C13-substitutions and their physico- and biochemical properties.

A mixture of pheophytins-a/a', metal-free forms of photosynthetically active chlorophyll(Chl)s-a/a' bearing the 13-methoxycarbonyl group, was substituted at the C13-position by bimolecular nucleophilic substitution with methyl bromoacetate or Michael addition with methyl acrylate, followed by C13-demethoxycarbonylation and magnesium insertion at the central position, to afford Chl-a/a' homologs possessing a methoxycarbonylmethyl or 2-methoxycarbonylethyl group at the C13-position, respectively. These C13-methylene- and ethylene-inserted homologs were characterized by 1D/2D H NMR spectroscopy, and the optical properties of their C13-epimerically pure samples are investigated using visible absorption, fluorescence emission, and circular dichroism spectroscopies. The stereochemistry at the C13-chiral center of these Chl-a/a' homologs was not inverted in a basic solution, and the Chl-a homologs were effective for the substrates for the chlorophyllase reaction, hydrolysis of the phytyl ester.

Influence of Living Environment during Childhood on Helicobacter pylori Infection in Japanese Young Adults.

Introduction: Helicobacter pylori infection is usually established during childhood, for which certain responsible environmental factors have been identified. However, the details of the infection routes remain unclear.

Objective: To determine the relation between H.

Stereoselective C3-substituent modification and substrate channeling by oxidoreductase BchC in bacteriochlorophyll a biosynthesis.

We report the in vitro activity of recombinant BchC oxidoreductase involved in bacteriochlorophyll a biosynthesis. BchC of Rhodobacter capsulatus preferentially oxidizes 3 R-3-(1-hydroxyethyl)-chlorophyllide a and 3 R-3-(1-hydroxyethyl)-bacteriochlorophyllide a in the presence of NAD to 3-acetyl-chlorophyllide a and bacteriochlorophyllide a, respectively, leaving the unreacted 3 S-epimers. In the reverse reaction, BchC with NADH predominately produces 3 R-epimeric alcohols from the 3-acetyl-(bacterio)chlorins.

Augmented antitumor activity of 5-fluorouracil by double knockdown of MDM4 and MDM2 in colon and gastric cancer cells.

Inactivation of the TP53 tumor suppressor gene is essential during cancer development and progression. Mutations of TP53 are often missense and occur in various human cancers. In some fraction of wild-type (wt) TP53 tumors, p53 is inactivated by upregulated murine double minute homolog 2 (MDM2) and MDM4.

Newly developed endoscopic detachable snare ligation therapy for colonic diverticular hemorrhage: a multicenter phase II trial (with videos).

Background And Aims: We previously reported preliminary safety results for a new method, endoscopic detachable snare ligation (EDSL), for diverticular hemorrhage. This method does not need endoscope removal to attach a ligation device after detection of the bleeding site. The aim of the present study was to evaluate the efficacy and safety of EDSL in a larger patient population.

MDM4 expression as an indicator of TP53 reactivation by combined targeting of MDM2 and MDM4 in cancer cells without TP53 mutation.

MDM2 and MDM4, a structurally related MDM2 homolog, negatively regulates expression and functions of TP53 tumor suppressor gene. To explore the precise expression patterns and function of MDM2 and MDM4 in wild-type (wt) TP53 cancer cells, we analyzed 11 various cancer cell lines with wt TP53. All cell lines exhibited deregulated expression of MDM2 and MDM4, and were divided into two distinct types; the one expressing high levels of MDM4 and another expressing low levels of MDM4.

Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

Up-regulated sirtuin 1 (SIRT1), an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer.

Effectiveness of an endoscopic biopsy procedure using EUS-FNA and EMR-C for diagnosing adenocarcinoma arising from ectopic pancreas: two case reports and a literature review.

Adenocarcinomas arising from the ectopic pancreas in the gastrointestinal wall are rarely described in the literature. In addition, obtaining an accurate preoperative diagnosis is difficult in most cases because these adenocarcinomas occur primarily in the submucosal layer and form submucosal tumors. Endoscopic ultrasonography-guided fine-needle aspiration and endoscopic mucosal resection with a transparent plastic cap-fitted panendoscope followed by a biopsy are useful for histological typing and making the differential diagnosis of adenocarcinoma, gastrointestinal stromal tumor, malignant lymphoma or other.

The sirtuin inhibitor tenovin-6 upregulates death receptor 5 and enhances cytotoxic effects of 5-fluorouracil and oxaliplatin in colon cancer cells.

It has been reported that upregulated SIRT1 (NAD(+)-dependent class III histone deacetylase) deacetylates the p53 protein, represses its function, and allows for tumor cell growth in various cancers. Here we investigated antitumor effects of tenovin-6, a small-molecule inhibitor of SIRT1 and SIRT2, in various colon cancer cell lines. Tenovin-6 induced apoptosis in all five colon cancer cell lines investigated (two cell lines with wild-type p53 and three with mutant p53) regardless of the p53 mutation status.

Predicting skin toxicity according to EGFR polymorphisms in patients with colorectal cancer receiving antibody against EGFR.

Background/aim: Monoclonal antibodies against epidermal growth factor receptor (EGFR) can extend progression-free survival (PFS) and overall survival (OS) in patients with unresectable colorectal cancer; however, skin toxicity often interferes with therapy continuation.

Patients And Methods: We analyzed the polymorphisms in EGFR and IgG fragment C receptor (FCGR) genes and determined their associations with clinical outcomes including PFS, OS, and skin toxicity. Five polymorphisms in EGFR and FCGR genes in 32 patients with unresectable colorectal cancer who were treated with antibodies against EGFR were examined.

A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S-1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric cancer.

Background: S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients.

Methods: In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v.

Synthesis of submicrometer-sized titania spherical particles with a sol-gel method and their application to colloidal photonic crystals.

A synthetic method for preparing submicrometer-sized titania particles is proposed, which is based on hydrolysis of titanium alkoxide with the use of a cosolvent and an amine catalyst for alkoxide hydrolysis. The preparation was performed with different amines of ammonia, methylamine (MA), and dimethylamine (DMA) in different solvents of ethanol/acetonitrile, ethanol/methanol, ethanol/acetone, ethanol/acetonitrile, and ethanol/formamide for 0.1-0.