Metabolomic profiling of urine-derived extracellular vesicles from rat model of drug-induced acute kidney injury.

Extracellular vesicles (EVs) are lipid bilayer particles that are released by various cells and provide a real-time snapshot of the state of these cells in tissue in a noninvasive manner. EVs contain components, including mRNA, miRNAs, proteins, and metabolites. Therefore, EVs hold promise for the discovery of liquid biopsy-based biomarkers for disease diagnosis. In the present study, metabolome analysis of urine EVs in rats with kidney injury caused by cisplatin and puromycin aminonucleoside was performed using liquid chromatography/mass spectrometry to identify candidate biomarkers that reflect the type and extent of injury in drug-induced nephrotoxicity. A total of 396 metabolites were detected in urine EVs, of which 65 were identified as potential biomarkers in urine EVs of drug-induced nephrotoxicity. Pathway analysis revealed that these metabolites may reflect changes occurring within damaged cells during kidney injury, suggesting that metabolomics of urine EVs could be a useful informative tool.

[A case of inoperable advanced bile duct cancer treated effectively with combined chemotherapy of gemcitabine and S-1].

The patient was a 63-year-old male. He was admitted to our department due to obstructive jaundice and acute renal failure, and was diagnosed with a lower bile duct cancer. As a result of a stent placement into the bile duct and hemodialysis, jaundice and renal failure improved. As scattered metastases were recognized on the superior surface of both hepatic lobes in intraoperative findings, only a portoenterostomy was performed. After that, 1,000 mg/m(2) of gemcitabine(day 1)and 60 mg/m(2) day of S-1(days 1-7)were administered repeatedly every other week as a course. One year and four months after the start of chemotherapy, radiation therapy of 40 Gy was performed at the site considered to be the remaining primary tumor according to the PET-CT findings. While chemotherapy was continued without change thereafter, the time passed with no visualization of lesions by CT. Two years and five months after the start of chemotherapy, duodenal stenosis and a metastasis in the liver occurred, resulting thereafter in aggravated conditions and death. The entire course lasted two years and eight months. We considered that combined therapy of gemcitabine and S-1 would be a useful option in chemotherapy for biliary tract cancer.

Helicobacter pylori-negative Gastric Adenocarcinoma Mimicking Verrucous Gastritis in the Antrum: A Case Report and Literature Review.

A 46-year-old man was referred to our hospital for the examination of a flat elevated lesion with an erosion-like depression, located on the greater curvature of the antrum. Endoscopic submucosal dissection was performed. Histological findings of the resected specimen demonstrated a well-differentiated tubular adenocarcinoma with a diameter of 12 mm. No atrophy was observed in the tumor-adjacent mucosa. Serum Helicobacter pylori antibody estimation and 13C-urea breath tests yielded negative results. Immunohistochemical staining was positive for both gastric mucin and intestinal mucin. The final diagnosis was well-differentiated tubular adenocarcinoma with a gastrointestinal phenotype that originated in mucosa uninfected by H. pylori.

The fibroblast growth factor homolog of Bombyx mori nucleopolyhedrovirus enhances systemic virus propagation in B. mori larvae.

All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast growth factor homolog (vFGF). Recently, we generated a Bombyx mori nucleopolyhedrovirus (BmNPV) mutant lacking functional vfgf and found that BmNPV vfgf contributes to virus virulence in B. mori larvae. However, the steps at which BmNPV vFGF works during in vivo virus infection were unclear. To uncover the role of vFGF during systemic infection of silkworm larvae, we generated a BmNPV mutant, BmIEGFP, possessing an ie-1 promoter-driven green fluorescent protein gene, and its derivative BmIEGFP/FGFD, in which vfgf was partially deleted from the genome of BmIEGFP. Intrahemocoelic and oral infection experiments using these viruses revealed that the loss of functional vFGF reduces viral infectivity in B. mori hemocytes. Our results suggest that BmNPV vFGF is required for efficient systemic infection, presumably by a chemotactic effect that allows budded virus to infect hemocytes efficiently.

Excellent prognosis of lepidic-predominant lung adenocarcinoma: low incidence of lymphatic vessel invasion as a key factor.

AIM: To clarify the prognostic value of predominant histological subtypes for small-sized lung adenocarcinoma. MATERIALS AND METHODS: Sixty-four specimens of resected invasive lung adenocarcinoma less than 20 mm in diameter with no lymph node metastasis were studied. These specimens were microscopically classified into predominant histological subtypes (21 lepidic, 16 acinar, 24 papillary, and three solid) according to the International association for the study of lung cancer/American thoracic society/European respiratory society adenocarcinoma classification. The relationships between tumor relapse and predominant histological subtypes were statistically analyzed. In addition the relationships between several pathological factors and predominant histological subtypes were statistically assessed. RESULTS: Kaplan-Meier relapse-free curves showed a five-year relapse-free rate of 100% in 64 patients with lepidic-predominant adenocarcinoma, compared with a rate of 73.7% (p=0.035 by log rank test) in patients with non-lepidic-predominant adenocarcinoma (papillary, acinar, and solid). The only statistically significant pathological factor between lepidic-predominant and non-lepidic-predominant histological subtypes was lymphatic vessel invasion as assessed by logistic regression analysis. CONCLUSION: In small-sized lung adenocarcinoma, lepidic-predominant histological subtype is the best prognostic factor, and a low incidence of lymphatic vessel invasion in the histological subtype is a key factor for an excellent prognosis.

Current-voltage characteristics of organic photovoltaic cells following deposition of cathode electrode.

The current-voltage characteristics of benzoporphine-fullerene solar cells were measured subsequent to the deposition of Al as a cathode material. Even in vacuum, a shift in the open circuit voltage was observed at 20 min after Al deposition. Moreover, the displacement of inert gases (N(2)or Ar) in the evaporation chamber enhanced the photovoltaic parameters. The power conversion efficiency was increased by 24% over the initial characteristics (from 1.04% to 1.29%), which indicates that the structure of the organic-metal interface changed rapidly after Al deposition, even if the process was performed in an air-free glovebox.

In vivo and in vitro analyses of a Bombyx mori nucleopolyhedrovirus mutant lacking functional vfgf.

All lepidopteran baculovirus genomes sequenced to date encode a viral fibroblast growth factor homolog (vfgf), suggesting that vfgf may play an important role in the infection cycle of lepidopteran baculoviruses. Here, we describe the characterization of a Bombyx mori nucleopolyhedrovirus (BmNPV) mutant lacking functional vfgf. We constructed a vfgf deletion mutant (BmFGFD) and characterized it in BmN cells and B. mori larvae. We observed that budded virus (BV) production was reduced in BmFGFD-infected BmN cells and B. mori larvae. The larval bioassays also revealed that deletion of vfgf did not reduce the infectivity; however, the mutant virus did take 20 h longer to kill B. mori larvae than wild-type BmNPV, when tested either by BV injection or by polyhedrin-inclusion body ingestion. These results suggest that BmNPV vfgf is involved in efficient virus production in BmN cells and B. mori larvae.

N-linked glycans of Bombyx mori nucleopolyhedrovirus fibroblast growth factor are crucial for its secretion.

Bombyx mori nucleopolyhedrovirus (BmNPV) fibroblast growth factor (BmFGF) is a glycosylated protein that is efficiently secreted into the medium. Here, we constructed mutant NPVs expressing His-tagged wild-type (wt) or mutant BmFGFs and showed that the two residues, asparagine 44 and 171, are the glycosylation sites of BmFGF. Also, removal of N-linked glycans from BmFGF resulted in almost complete inhibition of the secretion into the medium, suggesting that N-linked glycans of BmFGF are required for its secretion. These residues are not conserved in closely related Autographa californica NPV (AcMNPV)-encoded vFGF (AcFGF). Western blot analysis suggested that AcFGF is not glycosylated and is poorly secreted. A mutant AcFGF possessing two N-linked glycosylation sites was secreted into the medium more abundantly than that which occurred for wt AcFGF. This is the first direct evidence showing the role of N-linked glycans in the secretion process of a baculovirus protein.