Characterization of the Bacteriocinogenic Lactic Acid Bacteria Lactobacillus curvatus Strain Y108 Isolated from Nozawana-Zuke Pickles

We characterized the antibacterial activity of Lactobacillus curvatus strain Y108 isolated from the traditional Japanese pickle Nozawana-zuke, and partially identified the antibacterial agent produced by the strain. The Y108 strain exhibited antibacterial activity against L. curvatus JCM 1096, Listeria monocytogenes JCM7671, Staphylococcus aureus subsp. aureus JCM20624, and Serratia marcescens JCM20012. The antibacterial activity was abolished upon treatment with several proteases and lipase but not catalase, and it was moderately stable against heat treatment for 2 h at 100 degrees C. The Y108 strain showed higher antibacterial activity when grown at 20 degrees C than at 30 degrees C, which is its optimal growth temperature. SDS-PAGE analysis of the purified culture supernatant revealed the presence of two antibacterial peptide agents, F3-I and F3-II, with net molecular weights of 5.5 and 4.5 kDa, respectively. The IN-terminal amino acid sequences of F3-I and F3-II were homologous to those of lactocin 705 alpha and 705 beta, respectively. However, molecular masses and individual antibacterial activities of the two peptides were considerably different from those reported for lactocin 705.ArticleFOOD SCIENCE AND TECHNOLOGY RESEARCH. 16(3):253-262 (2010)journal articl

Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver

Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction

Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway

PARP inhibitors have changed the management of advanced high-grade epithelial ovarian cancer (EOC), especially homologous recombinant (HR)-deficient advanced high-grade EOC. However, the effect of PARP inhibitors on HR-proficient (HRP) EOC is limited. Thus, new therapeutic strategy for HRP EOC is desired. In recent clinical study, the combination of PARP inhibitors with anti-angiogenic agents improved therapeutic efficacy, even in HRP cases. These data suggested that anti-angiogenic agents might potentiate the response to PARP inhibitors in EOC cells. Here, we demonstrated that anti-angiogenic agents, bevacizumab and cediranib, increased the sensitivity of olaparib in HRP EOC cells by suppressing HR activity. Most of the γ-H2AX foci were co-localized with RAD51 foci in control cells. However, most of the RAD51 were decreased in the bevacizumab-treated cells. RNA sequencing showed that bevacizumab decreased the expression of CRY1 under DNA damage stress. CRY1 is one of the transcriptional coregulators associated with circadian rhythm and has recently been reported to regulate the expression of genes required for HR in cancer cells. We found that the anti-angiogenic agents suppressed the increase of CRY1 expression by inhibiting VEGF/VEGFR/PI3K pathway. The suppression of CRY1 expression resulted in decrease of HR activity. In addition, CRY1 inhibition also sensitized EOC cells to olaparib. These data suggested that anti-angiogenic agents and CRY1 inhibitors will be the promising candidate in the combination therapy with PARP inhibitors in HR-proficient EOC

Improved clonality detection in B-cell lymphoma using a semi-nested modification of the BIOMED-2 PCR assay for IGH rearrangement: A paraffin-embedded tissue study

The BIOMED-2 PCR protocol for targeting the IGH gene is widely employed for detecting clonality in B-cell malignancies. Unfortunately, the detection of clonality with this method is not very sensitive when paraffin sections are used as a DNA source. To increase the sensitivity, we devised a semi-nested modification of a JH consensus primer. The clonality detection rates of three assays were compared: the standard BIOMED-2, BIOMED-2 assay followed by BIOMED-2 re-amplification, and BIOMED-2 assay followed by semi-nested BIOMED-2. We tested more than 100 cases using paraffin-embedded tissues of various B-cell lymphomas, and found that the clonality detection rates with the above three assays were 63.9%, 79.6%, and 88.0%, respectively. While BIOMED-2 re-amplification was significantly more sensitive than the standard BIOMED-2, the semi-nested BIOMED-2 was significantly more sensitive than both the standard BIOMED-2 and BIOMED-2 re-amplification. An increase in sensitivity was observed in all lymphoma subtypes examined. In conclusion, tumor clonality may be detected in nearly 90% of B-cell lymphoma cases with semi-nested BIOMED-2. This ancillary assay may be useful when the standard BIOMED-2 fails to detect clonality in histopathologically suspected B-cell lymphomas

Paraimmunobiotic bifidobacteria modulate the expression patterns of peptidoglycan recognition proteins in porcine intestinal epitheliocytes and antigen presenting ells

Peptidoglycan recognition proteins (PGLYRPs) are a family of pattern recognition receptors (PRRs) that are able to induce innate immune responses through their binding to peptidoglycan (PGN), lipopolysaccharide, or lipoteichoic acid, or by interacting with other PRR-ligands. Recently, progress has been made in understanding the immunobiology of PGLYRPs in human and mice, however, their functions in livestock animals have been less explored. In this study, we characterized the expression patterns of PGLYRPs in porcine intestinal epithelial (PIE) cells and antigen-presenting cells (APCs) and their modulation by the interactions of host cells with PRR-ligands and non-viable immunomodulatory probiotics referred to as paraimmunobiotics. We demonstrated that PGLYRP-1, -2, -3, and -4 are expressed in PIE cells and APCs from Peyer?s patches, being PGLYPR-3 and -4 levels higher than PGLYRP-1 and -2. We also showed that PGLYRPs expression in APCs and PIE cells can be modulated by different PRR agonists. By using knockdown PIE cells for TLR2, TLR4, NOD1, and NOD2, or the four PGLYRPs, we demonstrated that PGLYRPs expressions would be required for activation and functioning of TLR2, TLR4, NOD1, and NOD2 in porcine epitheliocytes, but PGLYRPs activation would be independent of those PRR expressions. Importantly, we reported for the first time that PGLYRPs expression can be differentially modulated by paraimmunobiotic bifidobacteria in a strain-dependent manner. These results provide evidence for the use of paraimmunobiotic bifidobacteria as an alternative for the improvement of resistance to intestinal infections or as therapeutic tools for the reduction of the severity of inflammatory damage in diseases in which a role of PGLYRPs-microbe interaction has been demonstrated.Fil: Iida, Hikaru. Tohoku University; JapónFil: Tohno, Masanori. National Agriculture and Food Research Organization. Central Region Agricultural Research Centre; JapónFil: Islam, Md. Aminul. Tohoku University; Japón. Agricultural University. Faculty of Veterinary Science. Department of Medicine; BangladeshFil: Sato, Nana. Tohoku University; JapónFil: Kobayashi, Hisakazu. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Tohoku University; Japón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Humayun Kober, AKM. Tohoku University; JapónFil: Ikeda-Ohtsubo, Wakako. Tohoku University; JapónFil: Suda, Yoshihito. Miyagi University. Department of Food, Agriculture and Environment; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Nochi, Tomonori. Tohoku University; JapónFil: Miyazaki, Ayako. National Institute of Animal Health. Viral Diseases and Epidemiology Research Division; JapónFil: Uenishi, Hirohide. National Agriculture And Food Research Organization; JapónFil: Iwabuchi, Noriyuki. Morinaga Milk Industry Co., Ltd.; JapónFil: Xiao, Jin-zhong. Morinaga Milk Industry Co., Ltd.; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Solitary Peutz-Jeghers type hamartomatous polyps in the duodenum are not always associated with a low risk of cancer: two case reports

INTRODUCTION: A hamartomatous polyp without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome is diagnosed as a solitary Peutz-Jeghers type hamartomatous polyp. As compared with Peutz-Jeghers Syndrome, Peutz-Jeghers type hamartomatous polyps are diagnosed with a lower risk of cancer and are regarded as a different disorder. CASE PRESENTATION: In case one, we describe an 84-year-old Japanese man with a 14 mm duodenal polyp. Endoscopic mucosal resection was performed and histological examination showed findings suggestive of a hamartomatous polyp with a focus of well-differentiated adenocarcinoma. In case two, we describe a 76-year-old Japanese man who had been treated for prostate, rectal and lung cancer. Upper gastrointestinal endoscopy revealed a duodenal polyp measuring 15 mm in diameter. Endoscopic mucosal resection was performed, and histological examination showed findings suggestive of a hamartomatous polyp. Liver and thyroid cancers were found after the endoscopic treatment. CONCLUSION: Although duodenal solitary hamartomatous polyps are associated with a lower risk of cancer, four patients, including our cases, have been diagnosed with cancerous polyps. Patients with duodenal solitary hamartomatous polyps should be treated by endoscopic or surgical resection and need whole-body screening

Usefulness of Ω-shaped Incision in Skin Tumor Excision

Summary: We devised the Ω-shaped incision as a technique for skin tumor resection on the areas of skin with an arc-shaped fold. With this technique, the dog-ear that is formed during 6 wound closure can be resected within the range of the first skin incision. We report this technique after performing it on the face or trunk of 18 patients and confirmed its usefulness