Publications by authors named "Michio Sato"

81 Publications

Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria.

BMC Microbiol 2021 Aug 24;21(1):235. Epub 2021 Aug 24.

Department of Pharmaceutical Sciences, University of Shizuoka, 422-8526, Shizuoka, Japan.

Background: The Escherichia coli strain that is known to produce the genotoxic secondary metabolite colibactin is linked to colorectal oncogenesis. Therefore, understanding the properties of such colibactin-positive E. coli and the molecular mechanism of oncogenesis by colibactin may provide us with opportunities for early diagnosis or prevention of colorectal oncogenesis. While there have been major advances in the characterization of colibactin-positive E. coli and the toxin it produces, the infection route of the clb + strain remains poorly characterized.

Results: We examined infants and their treatments during and post-birth periods to examine potential transmission of colibactin-positive E. coli to infants. Here, analysis of fecal samples of infants over the first month of birth for the presence of a colibactin biosynthetic gene revealed that the bacterium may be transmitted from mother to infant through intimate contacts, such as natural childbirth and breastfeeding, but not through food intake.

Conclusions: Our finding suggests that transmission of colibactin-positive E. coli appears to be occurring at the very early stage of life of the newborn and hints at the possibility of developing early preventive measures against colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02292-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386082PMC
August 2021

Differentiation of THP-1 monocytes to macrophages increased mitochondrial DNA copy number but did not increase expression of mitochondrial respiratory proteins or mitochondrial transcription factor A.

Arch Biochem Biophys 2021 10 16;710:108988. Epub 2021 Jul 16.

School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan. Electronic address:

Monocytes are differentiated into macrophages. In this study, mitochondrial DNA copy number (mtDNAcn) levels and downstream events such as the expression of respiratory chain mRNAs were investigated during the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of monocytes. Although PMA treatment increased mtDNAcn, the expression levels of mRNAs encoded in mtDNA were decreased. The levels of mitochondrial transcription factor A mRNA and protein were also decreased. The levels of coenzyme Q10 remained unchanged. These results imply that, although mtDNAcn is considered as a health marker, the levels of mtDNAcn may not always be consistent with the parameters of mitochondrial functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2021.108988DOI Listing
October 2021

Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults.

BMC Microbiol 2021 Jun 28;21(1):196. Epub 2021 Jun 28.

Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan.

Background: Colibactin-producing Escherichia coli containing polyketide synthase (pks E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of pks E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals.

Results: Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of pks E. coli was determined by using specific primers for pks E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks E. coli was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of pks E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant.

Conclusions: These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02255-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240356PMC
June 2021

Structural determination of the sheath-forming polysaccharide of Sphaerotilus montanus using thiopeptidoglycan lyase which recognizes the 1,4 linkage between α-d-GalN and β-d-GlcA.

Int J Biol Macromol 2021 Jul 6;183:992-1001. Epub 2021 May 6.

Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya, Yokohama 240-8501, Japan. Electronic address:

Sphaerotilus natans is a filamentous sheath-forming bacterium commonly found in activated sludge. Its sheath is assembled from a thiolic glycoconjugate called thiopeptidoglycan. S. montanus ATCC-BAA-2725 is a sheath-forming member of stream biofilms, and its sheath is morphologically similar to that of S. natans. However, it exhibits heat susceptibility, which distinguishes it from the S. natans sheath. In this study, chemical composition and solid-state NMR analyses suggest that the S. montanus sheath is free of cysteine, indicating that disulfide linkage is not mandatory for sheath formation. The S. montanus sheath was successfully solubilized by N-acetylation, allowing solution-state NMR analysis to determine the sugar sequence. The sheath was susceptible to thiopeptidoglycan lyase prepared from the thiopeptidoglycan-assimilating bacterium, Paenibacillus koleovorans. The reducing ends of the enzymatic digests were labeled with 4-aminobenzoic acid ethyl ester, followed by HPLC. Two derivatives were detected, and their structures were determined. We found that the sheath has no peptides and is assembled as follows: [→4)-β-d-GlcA-(1→4)-β-d-Glc-(1→3)-β-d-GalNAc-(1→4)-α-d-GalNAc-(1→4)-α-d-GalN-(1→] (β-d-Glc and α-d-GalNAc are stoichiometrically and substoichiometrically 3-O-acetylated, respectively). Thiopeptidoglycan lyase was thus confirmed to cleave the 1,4 linkage between α-d-GalN and β-d-GlcA, regardless of the peptide moiety. Furthermore, vital fluorescent staining of the sheath demonstrated that elongation takes place at the tips, as with the S. natans sheath.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.05.001DOI Listing
July 2021

The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis.

Nat Commun 2021 05 5;12(1):2529. Epub 2021 May 5.

Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

In the past decade, many long noncoding RNAs (lncRNAs) have been identified and their in vitro functions defined, although in some cases their functions in vivo remain less clear. Moreover, unlike nuclear lncRNAs, the roles of cytoplasmic lncRNAs are less defined. Here, using a gene trapping approach in mouse embryonic stem cells, we identify Caren (short for cardiomyocyte-enriched noncoding transcript), a cytoplasmic lncRNA abundantly expressed in cardiomyocytes. Caren maintains cardiac function under pathological stress by inactivating the ataxia telangiectasia mutated (ATM)-DNA damage response (DDR) pathway and activating mitochondrial bioenergetics. The presence of Caren transcripts does not alter expression of nearby (cis) genes but rather decreases translation of an mRNA transcribed from a distant gene encoding histidine triad nucleotide-binding protein 1 (Hint1), which activates the ATM-DDR pathway and reduces mitochondrial respiratory capacity in cardiomyocytes. Therefore, the cytoplasmic lncRNA Caren functions in cardioprotection by regulating translation of a distant gene and maintaining cardiomyocyte homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22735-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099897PMC
May 2021

Isolation of New Colibactin Metabolites from Wild-Type and Trapping of a Mature Colibactin Derivative.

J Am Chem Soc 2021 04 31;143(14):5526-5533. Epub 2021 Mar 31.

Adenoprevent Co., Ltd., Shizuoka 422-8526, Japan.

Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis. Here, using the high-colibactin-producing wild-type strain we isolated from a clinical sample with the activity-based fluorescent probe we developed earlier, we were able to identify colibactin 770, which was recently identified and proposed as the complete form of colibactin, along with colibactin 788, 406, 416, 420, and 430 derived from colibactin 770 through structural rearrangements and solvolysis. Furthermore, we were able to trap the degrading mature colibactin species by converting the diketone moiety into quinoxaline in the crude culture extract to form colibactin 860 at milligram scale. This allowed us to determine the stereochemically complex structure of the rearranged form of an intact colibactin, colibactin 788, in detail. Furthermore, our study suggested that we were capturing only a few percent of the actual colibactin produced by the microbe, providing a crude quantitative insight into the inherent instability of this compound. Through the structural assignment of colibactins and their degradative products by the combination of LC-HRMS and NMR spectroscopies, we were able to elucidate further the fate of inherently unstable colibactin, which could help acquire a more complete picture of colibactin metabolism and identify key DNA adducts and biomarkers for diagnosing colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.1c01495DOI Listing
April 2021

Cesium-Catalyzed Hydrogen Production by the Gasification of Woody Biomass for Forest Decontamination.

ACS Omega 2021 Mar 16;6(8):5233-5243. Epub 2021 Feb 16.

Faculty of Symbiotic Systems Science, Fukushima University, 1 Kanayagawa, Fukushima, Fukushima 960-1296, Japan.

The large quantities of contaminated wood produced following the radioactive cesium decontamination of forests after the Fukushima Daiichi Nuclear Power Plant accident in 2011 can be used as a biomass resource for energy production via thermal treatment (e.g., gasification). To store the radioactive Cs ash produced from gasification, the immobilization of Cs in the pollucite structure is possible and requires stable Cs additives. In this study, a Cs additive (CsCO, CsCl, CsNO, or CsSO) was doped with timber waste sawdust (1-30 wt %). Fixed-bed downdraft-type continuous steam gasification experiments (0.7 g/min) showed that CsCO enhanced H production by 157% at 800 °C. X-ray absorption fine structure analysis and scanning electron microscopy observations revealed that the form of Cs on the surface of the char was CsCO, which provided the active sites for gasification acceleration. Thermogravimetric pyrolysis and CO gasification experiments showed that CsCO lowered the activation energy and frequency factor while also enhancing the reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c05237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931182PMC
March 2021

-Anisidine Dimer, 2-Methoxy--(2-methoxyphenyl) Benzene-1,4-diamine, in Rat Urine Associated with Urinary bladder Carcinogenesis.

Chem Res Toxicol 2021 03 15;34(3):912-919. Epub 2021 Feb 15.

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 4228526, Japan.

Monocyclic aromatic amines, -toluidine (-Tol) and its structural analog -anisidine (-Ans), are IARC Group 1 and Group 2A urinary bladder carcinogens, respectively, and are involved in metabolic activation and DNA damage. Our recent study revealed that 2-methyl--(2-methylphenyl) benzene-1,4-diamine (MMBD), a -semidine-type homodimer of -Tol, was detected and identified in an reaction of -Tol with S9 mix and urinary samples of -Tol-exposed rats. Potent mutagenic, genotoxic, and cytotoxic activities were reported with MMBD, suggesting its involvement in urinary bladder carcinogenesis. However, it remains unknown whether -Ans is converted to active metabolites to induce DNA damage in a similar manner as -Tol. In this study, we report that a novel -Ans metabolite, 2-methoxy--(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), a dimer by head-to-tail binding (-semidine form), was for the first time identified in -Ans-exposed rat urine. MxMxBD induced a stronger mutagenicity in -acetyltransferase overexpressed strains and potent genotoxicity and cytotoxicity in human bladder carcinoma T24 cells compared with -Ans. These results suggest that MxMxBD may to some extent contribute toward urinary bladder carcinogenesis. In addition to homodimerization, such as MxMxBD, heterodimerizations were observed when -Ans was coincubated with -Tol or aniline (Ani) in reactions with S9 mix. This study highlights the important consideration of homodimerizations and heterodimerizations of monocyclic aromatic amines, including -Ans, -Tol, and Ani, in the evaluation of the combined exposure risk of bladder carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrestox.0c00536DOI Listing
March 2021

Biosynthesis of the Immunosuppressant (-)-FR901483.

J Am Chem Soc 2021 01 29;143(1):132-136. Epub 2020 Dec 29.

Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

We report characterization of the biosynthetic pathway of the potent immunosuppressant (-)-FR901483 () through heterologous expression and enzymatic assays. The biosynthetic logic to form the azatricyclic alkaloid is consistent with those proposed in biomimetic syntheses and involves aza-spiro annulation of dityrosyl-piperazine to form a ketoaldehyde intermediate, followed by regioselective aldol condensation, stereoselective ketoreduction, and phosphorylation. A possible target of is proposed based on the biosynthetic studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c12352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094545PMC
January 2021

Specialized Flavoprotein Promotes Sulfur Migration and Spiroaminal Formation in Aspirochlorine Biosynthesis.

J Am Chem Soc 2021 01 22;143(1):206-213. Epub 2020 Dec 22.

Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Chemistry and Infection Biology (HKI), Beutenbergstrasse 11a, 07745 Jena, Germany.

Epidithiodiketopiperazines (ETPs) are a class of ecologically and medicinally important cyclodipeptides bearing a reactive transannular disulfide bridge. Aspirochlorine, an antifungal and toxic ETP isolated from used in sake brewing, deviates from the common ETP scaffold owing to its unusual ring-enlarged disulfide bridge linked to a spiroaminal ring system. Although this disulfide ring system is implicated in the biological activity of ETPs the biochemical basis for this derailment has remained a mystery. Here we report the discovery of a novel oxidoreductase (AclR) that represents the first-in-class enzyme catalyzing both a carbon-sulfur bond migration and spiro-ring formation, and that the pathway involves a cryptic acetylation as a prerequisite for the rearrangement. Genetic screening in identified as the candidate for the complex biotransformation, and the -deficient mutant provided the biosynthetic intermediate, unexpectedly harboring an acetyl group. In vitro assays showed that AclR alone promotes 1,2-sulfamyl migration, elimination of the acetoxy group, and spiroaminal formation. AclR features a thioredoxin oxidoreductase fold with a noncanonical CXXH motif that is distinct from the CXXC in the disulfide forming oxidase for the ETP biosynthesis. Crystallographic and mutational analyses of AclR revealed that the CXXH motif is crucial for catalysis, whereas the flavin-adenine dinucleotide is required as a support of the protein fold, and not as a redox cofactor. AclR proved to be a suitable bioinformatics handle to discover a number of related fungal gene clusters that potentially code for the biosynthesis of derailed ETP compounds. Our results highlight a specialized role of the thioredoxin oxidoreductase family enzyme in the ETP pathway and expand the chemical diversity of small molecules bearing an aberrant disulfide pharmacophore.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c08879DOI Listing
January 2021

Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.

Atherosclerosis 2020 12 2;315:18-23. Epub 2020 Nov 2.

Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan. Electronic address:

Background And Aims: Chronic low-grade inflammation is receiving much attention as a critical pathology that induces various aging phenotypes, a concept known as "inflammaging". Uremic patients undergoing hemodialysis therapy show vascular aging phenotypes characterized by greater arterial stiffness and calcification compared to healthy controls of the same generation. In the current study, we investigated whether levels of inflammaging markers in the circulation were associated with vascular aging phenotypes in hemodialysis patients, as estimated by the cardio-ankle vascular index (CAVI).

Methods: We conducted a multicenter cross-sectional study of 412 patients receiving hemodialysis and evaluated the relationship between circulating hs-CRP or ANGPTL2 levels, as markers of inflammaging, and CAVI.

Results: Of 412 patients, 376 were analyzed statistically. While circulating hs-CRP levels had no significant association with CAVI, generalized linear models revealed that high circulating ANGPTL2 levels were significantly associated with increasing CAVI after adjustment for classical metabolic factors and hemodialysis-related parameters [β 0.63 (95%CI 0.07-1.18)]. Exploratory analysis revealed that high circulating ANGPTL2 levels were also strongly associated with increased CAVI, particularly in patients with conditions of increased vascular mechanical stress, such elevated blood pressure [β 1.00 (95%CI 0.23-1.76)], elevated pulse pressure [β 0.75 (95%CI 0.52-0.98)], or excess body fluid [β 1.25 (95%CI 0.65-1.84)].

Conclusions: We conclude that circulating levels of ANGPTL2 rather than hs-CRP are positively associated with CAVI in the uremic population and that ANGPTL2 could be a unique marker of progression of vascular aging in patients receiving hemodialysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2020.10.890DOI Listing
December 2020

Stroma-derived ANGPTL2 establishes an anti-tumor microenvironment during intestinal tumorigenesis.

Oncogene 2021 01 13;40(1):55-67. Epub 2020 Oct 13.

Department of Molecular Genetics, Graduate School of Medical Science, Kumamoto University, Kumamoto, 860-8556, Japan.

Previous studies show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) functions as a tumor promoter in some cancer contexts. However, we recently reported that host ANGPTL2 also shows tumor suppressive activity by enhancing dendritic cell-mediated CD8 T cell anti-tumor immune responses in mouse kidney cancer and murine syngeneic models. However, mechanisms underlying ANGPTL2-mediated tumor suppression are complex and not well known. Here, we investigated ANGPTL2 tumor suppressive function in chemically-induced intestinal tumorigenesis. ANGPTL2 deficiency enhanced intestinal tumor growth in an experimental mouse colitis-associated colon cancer (CAC) model. Angptl2-deficient mice also showed a decrease not only in CD8 T cell responses but in CD4 T cell responses during intestinal tumorigenesis. Furthermore, we show that stroma-derived ANGPTL2 can activate the myeloid immune response. Notably, ANGPTL2 drove generation of immunostimulatory macrophages via the NF-κB pathway, accelerating CD4 T helper 1 (Th1) cell activation. These findings overall provide novel insight into the complex mechanisms underlying ANGPTL2 anti-tumor function in cancer pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-020-01505-7DOI Listing
January 2021

Association between dietary intake and the prevalence of tumourigenic bacteria in the gut microbiota of middle-aged Japanese adults.

Sci Rep 2020 09 16;10(1):15221. Epub 2020 Sep 16.

Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8636, Japan.

The relative contribution of diet to colorectal cancer (CRC) incidence is higher than that for other cancers. Animal models have revealed that Escherichia coli containing polyketide synthase (pks E. coli) in the gut participates in CRC development. The purpose of this cross-sectional study was to examine the relationship between dietary intake and the prevalence of pks E. coli isolated from the microbiota in faecal samples of 223 healthy Japanese individuals. Dietary intake was assessed using a previously validated brief-type self-administered diet history questionnaire. The prevalence of pks E. coli was evaluated using faecal samples collected from participants and specific primers that detected pks E. coli. The prevalence of pks E. coli was 26.9%. After adjusting for baseline confounders, the prevalence of pks E. coli was negatively associated with the intake of green tea (odds ratio [OR], 0.59 [95% confidence interval (CI) 0.30-0.88] per 100 g/1,000 kcal increment) and manganese (OR, 0.43 [95% CI 0.22-0.85] per 1 mg/1,000 kcal increment) and was positively associated with male sex (OR, 2.27 [95% CI 1.05-4.91]). While futher studies are needed to validate these findings, these results provide insight into potential dietary interventions for the prevention of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-72245-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495490PMC
September 2020

Bioconversion of biphenyl to a polyhydroxyalkanoate copolymer by Alcaligenes denitrificans A41.

AMB Express 2020 Aug 26;10(1):155. Epub 2020 Aug 26.

Microbial Genetics Laboratory, Department of Agricultural Chemistry, School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawsaki, Kanagawa, 214-8571, Japan.

A polyhydroxyalkanoate (PHA) copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)], was biosynthesized from biphenyl as the sole carbon source using Alcaligenes (currently Achromobacter) denitrificans A41. This strain is capable of degrading polychlorinated biphenyls (PCBs) and biphenyl. This proof-of-concept of the conversion of aromatic chemicals such as the environmental pollutant PCBs/biphenyl to eco-friendly products such as biodegradable polyester PHA was inspired by the uncovering of two genes encoding PHA synthases in the A. denitrificans A41 genome. When the carbon/nitrogen (C/N) ratio was set at 21, the cellular P(3HB-co-3HV) content in strain A41 reached its highest value of 10.1% of the cell dry weight (CDW). A two-step cultivation protocol improved the accumulation of P(3HB-co-3HV) by up to 26.2% of the CDW, consisting of 13.0 mol % 3HV when grown on minimum salt medium without nitrogen sources. The highest cellular content of P(3HB-co-3HV) (47.6% of the CDW) was obtained through the two-step cultivation of strain A41 on biphenyl as the sole carbon source. The purified copolymer had ultra-high molecular weight (weight-average molecular weight of 3.5 × 10), as revealed through gel-permeation chromatography. Based on the genomic information related to both polymer synthesis and biphenyl degradation, we finally proposed a metabolic pathway for the production of P(3HB-co-3HV) associated with the degradation of biphenyl by strain A41.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13568-020-01093-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450020PMC
August 2020

Total endoscopic thyroidectomy after open neck biopsy of the follicular lymphoma of the thyroid gland.

Asian J Endosc Surg 2021 Apr 12;14(2):275-278. Epub 2020 Aug 12.

Department of Surgery, International Goodwill Hospital, Yokohama, Japan.

Remote-access total endoscopic thyroidectomy (TET) is a recently established approach that can avoid producing scars in the neck. There are no clear surgical indications for TET for benign nodules or for malignant tumors at present. We report a successful TET in a 50-year-old Japanese woman with follicular lymphoma of the thyroid gland after an open neck biopsy. She had been referred to us with a neck tumor noted 2 months earlier. Because of adhesion, we performed a combined resection of the thyroid and partial right sternohyoid muscle. To the best of our knowledge, there is no other report of a TET performed after open neck surgery. Our patient's case demonstrates that (a) the cosmetic outcome of TET is clearly superior to that of conventional open neck surgery, and (b) a TET can be suitable even for reoperation if carefully selected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ases.12847DOI Listing
April 2021

Characterization of Colibactin-Producing Escherichia coli Isolated from Japanese Patients with Colorectal Cancer.

Jpn J Infect Dis 2020 Nov 29;73(6):437-442. Epub 2020 May 29.

Department of Pharmaceutical Sciences, University of Shizuoka, Japan.

We investigated the relationship between colibactin-producing (clb) Escherichia coli and colorectal adenocarcinoma. In total, 729 E. coli colonies were isolated from tumor and surrounding non-tumor regions in resected specimens from 34 Japanese patients; 450 colonies were from the tumor regions and 279 from the non-tumor regions. clb bacteria were found in tumor regions of 11 patients (11/34, 32.4%) and they were also detected in the non-tumor regions of 7 out of these 11 patients (7/34, 20.6%). The prevalence of clb isolates was 72.7% (327/450) and 44.1% (123/279) in tumor and non-tumor regions, respectively. All the recovered clb isolates belonged to the phylogenetic group B2 and were the most predominant type in tumor regions. Hemolytic (α-hemolysin-positive, hlyA) and non-hemolytic (α-hemolysin-negative, hlyA) clb isolates were obtained from patient #19; however, the prevalence of hlyA clb isolates was significantly higher in tumor regions (35/43, 81.4%) than in non-tumor regions (3/19, 15.8%). Moreover, a significantly higher production of N-myristoyl-D-asparagine, a by-product of colibactin biosynthesis, was observed in hlyA clb isolates than in hlyA clb isolates. Our results suggest that hlyA clb E. coli may have a selective advantage in colorectal colonization and, consequently, might play a role in carcinogenesis. The presence of hlyA clb bacteria in healthy individuals is a potential risk marker of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7883/yoken.JJID.2020.066DOI Listing
November 2020

Heterochronous Suture Line Recurrences in the Jejunal Pouch following Total Gastrectomy for Stage II Gastric Cancer: A Case Report and Literature Review.

Case Rep Oncol 2020 Jan-Apr;13(1):225-232. Epub 2020 Mar 19.

Department of Surgery, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan.

We report the case of a 65-year-old male who developed heterochronous local recurrences of gastric cancer in the jejunal pouch (J-pouch) four times after total gastrectomy. He underwent total gastrectomy, J-pouch, and Roux-en-Y reconstruction for stage II gastric cancer in 2005. Four local recurrences appeared on the esophago-jejunal anastomosis, the suture line within the pouch, the esophago-jejunal anastomosis, and the anastomosis between the jejunum and Y-loop, which were resected by partial excision or endoscopic submucosal dissection. Suture line recurrence of gastric cancer is rare. The common features for each recurrence included the surgically negative resection margins, observation of the same histopathological subtype, absence of remote metastasis or peritoneal seeding, and the recurrence on the anastomotic suture line, suggesting that the cause of recurrence was the implantation of exfoliated cancer cells probably in the suture line. However, there is no established procedure for preventing implantation recurrence currently, the effectiveness of lumen lavage is suggested.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000505392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154264PMC
March 2020

Elevated levels of proinflammatory volatile metabolites in feces of high fat diet fed KK-A mice.

Sci Rep 2020 03 30;10(1):5681. Epub 2020 Mar 30.

School of Food Nutritional Sciences, Shizuoka, Japan.

When the microfloral composition deteriorates, it triggers low-level chronic inflammation associated with several lifestyle-related diseases including obesity and diabetic mellitus. Fecal volatile organic compounds (VOCs) have been found to differ in gastrointestinal diseases as well as intestinal infection. In this study, to evaluate a potential association between the pathogenesis of lifestyle-related diseases and VOCs in the intestinal tract, fecal VOCs from obese/diabetic KK-A mice (KK) or controls (C57BL/6J mice; BL) fed a normal or high fat diet (NFD or HFD) were investigated using headspace sampler-GC-EI-MS. Principal component analysis (PCA) of fecal VOC profiles clearly separated the experimental groups depending on the mouse lineage (KK vs BL) and the diet type (NFD vs HFD). 16 s rRNA sequencing revealed that the PCA distribution of VOCs was in parallel with the microfloral composition. We identified that some volatile metabolites including n-alkanals (nonanal and octanal), acetone and phenol were significantly increased in the HFD and/or KK groups. Additionally, these volatile metabolites induced proinflammatory activity in the RAW264 murine macrophage cell line indicating these bioactive metabolites might trigger low-level chronic inflammation. These results suggest that proinflammatory VOCs detected in HFD-fed and/or diabetic model mice might be novel noninvasive diagnosis biomarkers for diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-62541-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105489PMC
March 2020

Genotyping of a gene cluster for production of colibactin and in vitro genotoxicity analysis of strains obtained from the Japan Collection of Microorganisms.

Genes Environ 2020 11;42:12. Epub 2020 Mar 11.

2Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.

Introduction: Colibactin is a small genotoxic molecule produced by enteric bacteria, including certain () strains harbored in the human large intestine. This polyketide-peptide genotoxin is considered to contribute to the development of colorectal cancer. The colibactin-producing ( ) microorganisms possess a 54-kilobase genomic island ( gene cluster). In the present study, to assess the distribution of the gene cluster, genotyping analysis was carried out among strains randomly chosen from the Japan Collection of Microorganisms, RIKEN BRC, Japan.

Findings: The analysis revealed that two of six strains possessed a gene cluster. These strains JCM5263 and JCM5491 induced genotoxicity in in vitro micronucleus (MN) tests using rodent CHO AA8 cells. Since the induction level of MN by JCM5263 was high, a bacterial test was carried out with a cell extract of the strain, revealing that the extract had SOS-inducing potency in the tester bacterium.

Conclusion: These results support the observations that the gene cluster is widely distributed in nature and having genotoxic potencies is not rare among microorganisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s41021-020-00149-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065307PMC
March 2020

A new class of dimeric product isolated from the fungus Chaetomium globosum: evaluation of chemical structure and biological activity.

J Antibiot (Tokyo) 2020 05 5;73(5):320-323. Epub 2020 Feb 5.

Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.

Chaetomium globosum is a filamentous fungus from which we have previously isolated a series of interesting natural products. Here, we isolated a previously unknown natural product from the culture of C. globosum. Through spectroscopic and crystallographic characterization, we determined the compound to be a new dimerized azaphilone-type product which we termed cochliodone J (1). Furthermore, our investigation into the biological activity of the natural product determined that 1 was cytotoxic to human cervix carcinoma HeLa cells with an IC of 17.3 µM. Lastly, a plausible biosynthetic mechanism for 1 is suggested based on our previous study on the biosynthesis of a closely related compound, cochliodone A (2).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41429-020-0281-xDOI Listing
May 2020

Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study.

Nephrol Dial Transplant 2020 05;35(5):854-860

Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Background: Patients undergoing hemodialysis treatment have a poor prognosis, as many develop premature aging. Systemic inflammatory conditions often underlie premature aging phenotypes in uremic patients. We investigated whether angiopoietin-like protein 2 (ANGPTL 2), a factor that accelerates the progression of aging-related and noninfectious inflammatory diseases, was associated with increased mortality risk in hemodialysis patients.

Methods: We conducted a multicenter prospective cohort study of 412 patients receiving maintenance hemodialysis and evaluated the relationship between circulating ANGPTL2 levels and the risk for all-cause mortality. Circulating ANGPTL2 levels were log-transformed to correct for skewed distribution and analyzed as a continuous variable.

Results: Of 412 patients, 395 were included for statistical analysis. Time-to-event data analysis showed high circulating ANGPTL2 levels were associated with an increased risk for all-cause mortality after adjustment for age, sex, hemodialysis vintage, nutritional status, metabolic parameters and circulating high-sensitivity C-reactive protein levels {hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.10-3.77]}. High circulating ANGPTL2 levels were also strongly associated with an increased mortality risk, particularly in patients with a relatively benign prognostic profile [HR 3.06 (95% CI 1.86-5.03)]. Furthermore, the relationship between circulating ANGPTL2 levels and mortality risk was particularly strong in patients showing few aging-related phenotypes, such as younger patients [HR 7.99 (95% CI 3.55-18.01)], patients with a short hemodialysis vintage [HR 3.99 (95% CI 2.85-5.58)] and nondiabetic patients [HR 5.15 (95% CI 3.19-8.32)].

Conclusion: We conclude that circulating ANGPTL2 levels are positively associated with mortality risk in patients receiving maintenance hemodialysis and that ANGPTL2 could be a unique marker for the progression of premature aging and subsequent mortality risk in uremic patients, except those with significant aging-related phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfz236DOI Listing
May 2020

In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient.

J Toxicol Sci 2019 ;44(12):871-876

Department of Pharmaceutical Sciences, University of Shizuoka.

Colibactin is a polyketide-peptide genotoxin produced by enteric bacteria such as E. coli, and is considered to contribute to the development of colorectal cancer. We previously isolated E. coli strains from Japanese colorectal cancer patients, and in the present study we investigated the genotoxic potency of the colibactin-producing (clb) E. coli strains that carry the polyketide synthases "pks" gene cluster (pks) and an isogenic clb mutant in which the colibactin-producing ability is impaired. Measurement of phosphorylated histone H2AX indicated that DNA double strand breaks were induced in mammalian CHO AA8 cells infected with the clb E. coli strains. Induction of DNA damage response (SOS response) by crude extract of the clb strains was 1.7 times higher than that of the clb E. coli in an umu assay with a Salmonella typhimurium TA1535/pSK1002 tester strain. Micronucleus test with CHO AA8 cells revealed that infection with the clb strains induced genotoxicity, i.e., the frequencies of micronucleated cells infected with clb strain were 4-6 times higher than with the clb strain. Since the intestinal flora are affected by dietary habits that are strongly associated with ethnicity, these data may contribute to both risk evaluation and prevention of colorectal cancer in the Japanese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2131/jts.44.871DOI Listing
April 2020

Aging- and obesity-related peri-muscular adipose tissue accelerates muscle atrophy.

PLoS One 2019 23;14(8):e0221366. Epub 2019 Aug 23.

Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221366PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707561PMC
March 2020

Treatment of aortoesophageal fistula developed after thoracic endovascular aortic repair: a questionnaire survey study.

Esophagus 2020 01 20;17(1):81-86. Epub 2019 Jun 20.

The Japan Esophageal Society, 2-3-13 Taihei, Sumida-ku, Tokyo, 103-0012, Japan.

Background: Aortoesophageal fistula (AEF) is a life-threatening late complication that can occur after thoracic endovascular aortic repair (TEVAR). More data are required to identify the optimal treatment strategy for AEF developed after TEVAR. The aim of this study was to clarify the current status of surgical treatments for AEF developed after TEVAR and the outcomes of these treatments.

Methods: The Japan Esophageal Society conducted a questionnaire survey targeting authorized or semi-authorized institutes at Authorized Institutes for Board Certified Esophageal Surgeons. Thirty-nine patients with AEF developed after TEVAR were identified from 15 institutes. Data on patient demographics, treatment performed, and survival rate were obtained by the questionnaire. The Kaplan-Meier method was used for survival analysis and differences in the survival rates.

Results: Esophagectomy and aortic replacement were performed in 32 and 22 patients, respectively, and 22 underwent both procedures. Postoperative complications were observed in 24 patients (75.0%). Complications with Clavien-Dindo Grade III or higher were observed in 53.1% of patients. Operative and hospital mortality rates were 3.1% and 18.8%, respectively. The survival rate in patients who underwent esophagectomy was higher than in those who did not (P < 0.0001). The survival of patients who underwent both esophagectomy and aortic replacement was also higher than in those who did not (P < 0.0001).

Conclusion: Esophagectomy combined with aortic replacement can offer a long-term treatment strategy with higher survival rates in patients who develop AEF after TEVAR. Because of the high incidence of postoperative morbidity and mortality, these types of surgery should only be performed in centers with both experienced esophageal and cardiovascular surgical teams.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10388-019-00683-yDOI Listing
January 2020

Activity-Based Probe for Screening of High-Colibactin Producers from Clinical Samples.

Org Lett 2019 06 13;21(12):4490-4494. Epub 2019 Jun 13.

Department of Pharmaceutical Sciences , University of Shizuoka , Shizuoka 422-8526 , Japan.

While high-colibactin-producing Escherichia coli is thought to be associated with colorectal oncogenesis, this study is complicated part due to an inability to isolate colibactin adequately. Here, we created fluorescent probes activated by ClbP, the colibactin-maturing peptidase, to identify high-colibactin-producing strains. Our probe served as a valuable clinical diagnostic tool that allowed simple high-throughput diagnostic screening of clinical samples. Furthermore, the probe also allowed identification of high-colibactin producers that would help advance our understanding of colibactin biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b01345DOI Listing
June 2019

Alzheimer Aβ Assemblies Accumulate in Excitatory Neurons upon Proteasome Inhibition and Kill Nearby NAKα3 Neurons by Secretion.

iScience 2019 Mar 28;13:452-477. Epub 2019 Feb 28.

Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address:

We identified ∼30-mer amyloid-β protein (Aβ) assemblies, termed amylospheroids, from brains of patients with Alzheimer disease (AD) as toxic entities responsible for neurodegeneration and showed that Na,K-ATPase α3 (NAKα3) is the sole target of amylospheroid-mediated neurodegeneration. However, it remains unclear where in neurons amylospheroids form and how they reach their targets to induce neurodegeneration. Here, we present an in vitro culture system designed to chronologically follow amylospheroid formation in mature neurons expressing amyloid precursor protein bearing early-onset AD mutations. Amylospheroids were found to accumulate mainly in the trans-Golgi network of excitatory neurons and were initially transported in axons. Proteasome inhibition dramatically increased amylospheroid amounts in trans-Golgi by increasing Aβ levels and induced dendritic transport. Amylospheroids were secreted and caused the degeneration of adjacent NAKα3-expressing neurons. Interestingly, the ASPD-producing neurons later died non-apoptotically. Our findings demonstrate a link between ASPD levels and proteasome function, which may have important implications for AD pathophysiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isci.2019.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443839PMC
March 2019

Identifying the Biosynthetic Gene Cluster for Triacsins with an N-Hydroxytriazene Moiety.

Chembiochem 2019 05 18;20(9):1145-1149. Epub 2019 Mar 18.

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, 2151 Berkeley Way, Berkeley, CA, 94704, USA.

Triacsins are a family of natural products having in common an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, their biosynthesis has remained unknown. Here we report the identification of the triacsin biosynthetic gene cluster in Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producer Streptomyces tsukubaensis NRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performed in vivo to advance the understanding of N-hydroxytriazene biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbic.201800762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590916PMC
May 2019

Biosynthesis of lagopodins in mushroom involves a complex network of oxidation reactions.

Org Biomol Chem 2019 01;17(2):234-239

Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

Use of the ku70-deficient strain of Coprinopsis cinerea enabled confirmation within the native context of the central role the sesquiterpene synthase Cop6 plays in lagopodin biosynthesis. Furthermore, yeast in vivo bioconversion and in vitro assays of two cytochrome P450 monooxygenases Cox1 and Cox2 allowed elucidation of the network of oxidation steps that build structural complexity onto the α-cuprenene framework during the biosynthesis of lagopodins. Three new compounds were identified as intermediates formed by the redox enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8ob02814aDOI Listing
January 2019

Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice.

Circ J 2019 01 27;83(2):368-378. Epub 2018 Nov 27.

Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University.

Background: The rapid increase in the number of heart failure (HF) patients in parallel with the increase in the number of older people is receiving attention worldwide. HF not only increases mortality but decreases quality of life, creating medical and social problems. Thus, it is necessary to define molecular mechanisms underlying HF development and progression. HMGB2 is a member of the high-mobility group superfamily characterized as nuclear proteins that bind DNA to stabilize nucleosomes and promote transcription. A recent in vitro study revealed that HMGB2 loss in cardiomyocytes causes hypertrophy and increases HF-associated gene expression. However, it's in vivo function in the heart has not been assessed. Methods and Results: Western blotting analysis revealed increased HMGB2 expression in heart tissues undergoing pressure overload by transverse aorta constriction (TAC) in mice. Hmgb2 homozygous knockout (Hmgb2) mice showed cardiac dysfunction due to AKT inactivation and decreased sarco(endo)plasmic reticulum Ca-ATPase (SERCA)2a activity. Compared to wild-type mice, Hmgb2 mice had worsened cardiac dysfunction after TAC surgery, predisposing mice to HF development and progression.

Conclusions: This study demonstrates that upregulation of cardiac HMGB2 is an adaptive response to cardiac stress, and that loss of this response could accelerate cardiac dysfunction, suggesting that HMGB2 plays a cardioprotective role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-18-0925DOI Listing
January 2019

Disinfection by Ozone Microbubbles Can Cause Morphological Change of f. sp. Spores.

Plant Pathol J 2018 Aug 1;34(4):335-340. Epub 2018 Aug 1.

School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571, Japan.

To investigate the difference in the disinfectant efficiency of ozone microbubbles (OMB) and ozone millibubbles (OMMB), the morphological change of the treated f. sp. spores was observed with scanning and transmission electron microscopies (SEM and TEM). The disinfectant efficiency of OMB on f. sp. spores was greater than that of OMMB. On observation with SEM, it was revealed that morphological change of f. sp. spores was caused by OMB and OMMB, and damage to the spore surfaces by OMB occurred sooner than that by OMMB. On observation with TEM, it was furthermore confirmed that f. sp. spores treated with OMB induced wavy deformation of cell membrane and the intracellular change different from that with OMMB. Therefore, the greater disinfection efficiency of OMB was suggested to be caused due to the function of the MB in addition to the oxidative power of O.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5423/PPJ.NT.11.2017.0234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097823PMC
August 2018
-->