Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenicEscherichia coli-mediated inflammation

Background: Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogenassociated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB). Results: All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1! and MCP-1 in BIE cells by activating both NF-"B and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-"B and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3). Conclusions: BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.Fil: Takanashi, Naoya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tomosada, Yohsuke. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Tucuman. Centro de Referencia Para Lactobacilos (i); Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Murata, Kozue. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Takahashi, Takuya. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Chiba, Eriko. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tohno, Masanori. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; National Agriculture and Food Research Organization. National Institute of Livestock and Grassland Science; Japan.;Fil: Tomoyuki Shimazu. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan; Laboratory of Animal Breading and Genetics. Graduate School of Agricultural Science; Japan.;Fil: Aso, Hisashi. Cell Biology Laboratory, Graduate School of Agricultural Science. Tohoku University; Japan.;Fil: Suda, Yoshihito. Department of Food, Agriculture and Environment. Miyagi University; Japan.;Fil: Ikegami, Shuji. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Itoh, Hiroyuki. Division of Research and Development. Food Science Institut. Meiji Dairies CoOdawara; Japan;Fil: Kawai, Yasushi. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Tadao Saito. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan;Fil: Alvarez, Gladis Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); Argentina;Fil: Kitazawa, Haruki. Food and Feed Immunology Group. Laboratory of Animal Products Chemistry. Graduate School of Agricultural Science. Tohoku University; Japan

Malignant transformation arising from mature cystic teratoma of the ovary presenting as ovarian torsion: a case report and literature review

Objective: Ovarian torsion is an acute gynecological condition. Torsion is more likely to occur with benign rather than malignant tumors. Mature cystic teratoma of the ovary (MCTO) is frequent in women of reproductive age; however, the incidence of malignant transformation is approximately 2%. We report a case of malignant transformation of MCTO presenting as ovarian tumor torsion. Case report: A 51-year-old premenopausal woman was diagnosed with mature cystic teratoma in the left ovary 7 years ago. The patient visited our hospital because she had been experiencing of pain in left lower abdomen for the past two days. She was diagnosed with ovarian tumor torsion and underwent emergency surgery. The left ovarian tumor was twisted, and left salpingo-oophorectomy was performed. Histopathological examination revealed squamous cell carcinoma arising from the MCTO. We carefully followed the patients without performing staging laparotomy. On postoperative day 112, multiple lymph node metastases in the pelvic and para-aortic areas were found by positron-emission tomography and computed tomography. After referral to a university hospital, total hysterectomy, right salpingo-oophorectomy, partial omentectomy, and pelvic and paraaortic lymphadenectomy were performed. Metastases of squamous cell carcinoma were confirmed in the pelvic and para-aortic lymph nodes. Six courses of adjuvant chemotherapy with paclitaxel and carboplatin were given following radical surgery to prevent the recurrence of malignant transformation of MCTO. No recurrence of the disease has been observed during 2 years of follow-up. Conclusio: When physicians diagnose large ovarian tumor torsion cases, preoperative examinations should be performed, with the possibility of malignancy in mind

A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm

High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis

Purpose: Vitreoretinal lymphoma (VRL) is a non-Hodgkin lymphoma of the diffuse large B cell type (DLBCL), which is an aggressive cancer causing central nervous system related mortality. The pathogenesis of VRL is largely unknown. The role of microRNAs (miRNAs) has recently acquired remarkable importance in the pathogenesis of many diseases including cancers. Furthermore, miRNAs have shown promise as diagnostic and prognostic markers of cancers. In this study, we aimed to identify differentially expressed miRNAs and pathways in the vitreous and serum of patients with VRL and to investigate the pathogenesis of the disease. Materials and Methods: Vitreous and serum samples were obtained from 14 patients with VRL and from controls comprising 40 patients with uveitis, 12 with macular hole, 14 with epiretinal membrane, 12 healthy individuals. The expression levels of 2565 miRNAs in serum and vitreous samples were analyzed. Results: Expression of the miRNAs correlated significantly with the extracellular matrix (ECM) ‒receptor interaction pathway in VRL. Analyses showed that miR-326 was a key driver of B-cell proliferation, and miR-6513-3p could discriminate VRL from uveitis. MiR-1236-3p correlated with vitreous interleukin (IL)-10 concentrations. Machine learning analysis identified miR-361-3p expression as a discriminator between VRL and uveitis. Conclusions: Our findings demonstrate that aberrant microRNA expression in VRL may affect the expression of genes in a variety of cancer-related pathways. The altered serum miRNAs may discriminate VRL from uveitis, and serum miR-6513-3p has the potential to serve as an auxiliary tool for the diagnosis of VRL

Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. We performed a comprehensive analysis of 2565 miRNAs from biopsy and serum specimens of 17 cases with IgG4-ROD, where 21 cases with orbital MALT lymphoma were performed. We identified specific miRNA signatures and their miRNA target pathways, as well as the network analysis for IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. Enrichment analyses of biological pathways showed that the longevity-regulating pathway in IgG4-ROD and the mitogen-activated protein kinase (MAPK) signaling pathway in orbital MALT lymphoma was most enriched by target genes of downregulated miRNAs. This is the first evidence of miRNA profiles of biopsy and serum specimens of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating the pathogenesis of these disorders