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Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.

Head and neck squamous cell carcinoma (HNSCC) has a high capacity for invasion. To identify microRNAs (miRNAs) that regulate HNSCC invasion, we compared miRNA expression profiles between a parent HNSCC cell line and a highly invasive clone. The miR-200 family and miR-203 were downregulated in the clone. Here we focused on the role of miR-203 in invasion and epithelial-mesenchymal transition (EMT) induction in HNSCC. miR-203 was downregulated during EMT induction. Moreover, ectopic overexpression of miR-203 suppressed the invasion and induced mesenchymal-epithelial transition (MET) in HNSCC cells. Interestingly, we identified NUAK family SNF1-like kinase 1 (NUAK1) as a novel target gene of miR-203 by cyclopedic analysis using anti-Ago2 antibody. Increased expression of NUAK1 was observed during EMT induction, and ectopic expression of miR-203 delayed EMT induction by suppressing NUAK1 expression. Moreover, NUAK1 overexpression promoted the invasion of HNSCC cells. Importantly, NUAK1 expression was well correlated with poor differentiation, invasiveness, and lymph node metastasis in HNSCC cases. Overall, miR-203 has a tumor-suppressing role in invasion and EMT induction by targeting NUAK1 in HNSCC, suggesting miR-203 as a potential new diagnostic and therapeutic target for the treatment of HNSCC.

A red blood cell (RBC) from human exhibited direct electron transfer (DET) activity on a bare indium tin oxide (ITO) electrode. A formal potential of 0.152 V vs. a silver-silver chloride saturated potassium chloride (AglAgClIKCI(satd.)) was estimated for the human RBC (type AB) from a pair of redox peaks at around 0.089 and 0.215 V (vs. AglAgClIKC1(satd.)) on cyclic voltammetric (CV) measurements in a phosphate buffered saline (PBS; 39 mM; pH 7.4) solution. The results agreed well with those of a redox couple for iron-bearing heme groups in hemoglobin molecules (HbFe(1I)/HbFe(III)) on the bare ITO electrodes, indicated that DET active species were hemoglobin (Hb) molecules encapsulated by a phospholipid bilayer membrane of the human BBC. The quantity of electrochemically active Hb in the human RBC was estimated to be 30 pmol cm(-2). In addition, the human RBC exhibited oxygen reduction reaction (ORR) activity in the dioxygen (O2) saturated PBS solution at the negative potential from ca. 0.15 V (vs. AglAgClIKC1(satd.)). A single cell test proved that a biofuel cell (BFC) with an O2IRBCIITO cathode showed the open-circuit voltage (OCV) of ca. 0.43 V and the maximum power density of ca. 0.6811W cm(-2)., Article, BIOSENSORS & BIOELECTRONICS. 55:14-18 (2014)

We prepared hybrid systems of chiral Schiff base Cu(II) complexes incorporating threonine derivatives Schiff base and micro particles of TiO2. Under N2 atmosphere, it has been known UV light irradiation resulting in photo-induced reduction reaction of Cu(II) species to Cu(I) ones. In this study, we have investigated conditions of redox reactions in view of concentration of reactive species and reversible or irreversible exchanging ligands. We could summarize proposed reaction mechanism by present information.

The conversion of soluble, nontoxic amyloid β-proteins (Aβ) to aggregated, toxic forms rich in β-sheets is considered to be a key step in the development of Alzheimer's disease. Accumulating evidence suggests that lipid-protein interactions play a crucial role in the aggregation of amyloidogenic proteins like Aβ. Our group has previously reported that amyloid fibrils of Aβ formed on membranes containing clusters of GM1 ganglioside (M-fibrils) exhibit greater cytotoxicity than fibrils formed in aqueous solution (W-fibrils) [ Okada ( 2008 ) J. Mol. Biol. 382 , 1066 - 1074 ]. W-fibrils are considered to consist of in-register parallel β-sheets. However, the precise molecular structure of M-fibrils and force driving the formation of toxic fibrils remain unclear. In this study, we hypothesized that low-polarity environments provided by GM1 clusters drive the formation of toxic fibrils and compared the structure and cytotoxicity of W-fibrils, M-fibrils, and aggregates formed in a low-polarity solution mimicking membrane environments. First, we determined solvent conditions which mimic the polarity of raftlike membranes using Aβ-(1-40) labeled with the 7-diethylaminocoumarin-3-carbonyl dye. The polarity of a mixture of 80% 1,4-dioxane and 20% water (v/v) was found to be close to that of raftlike membranes. Aβ-(1-40) formed amyloid fibrils within several hours in 80% dioxane (D-fibrils) or in the presence of raftlike membranes, whereas a much longer incubation time was required for fibril formation in a conventional buffer. D-fibrils were morphologically similar to M-fibrils. Fourier-transform infrared spectroscopy suggested that M-fibrils and D-fibrils contained antiparallel β-sheets. These fibrils had greater surface hydrophobicity and exhibited significant toxicity against human neuroblastoma SH-SY5Y cells, whereas W-fibrils with less surface hydrophobicity were not cytotoxic. We concluded that ganglioside clusters mediate the formation of toxic amyloid fibrils of Aβ with an antiparallel β-sheet structure by providing less polar environments.

It is widely accepted that the conversion of the soluble, nontoxic amyloid β-protein (Aβ) monomer to aggregated toxic Aβ rich in β-sheet structures is central to the development of Alzheimer's disease. However, the mechanism of the abnormal aggregation of Aβ in vivo is not well understood. We have proposed that ganglioside clusters in lipid rafts mediate the formation of amyloid fibrils by Aβ, the toxicity and physicochemical properties of which are different from those of amyloids formed in solution. In this paper, the mechanism by which Aβ-(1-40) fibrillizes in raftlike lipid bilayers composed of monosialoganglioside GM1, cholesterol, and sphingomyelin was investigated in detail on the basis of singular-value decomposition of circular dichroism data and analysis of fibrillization kinetics. At lower protein densities in the membrane (Aβ:GM1 ratio of less than ∼0.013), only the helical species exists. At intermediate protein densities (Aβ:GM1 ratio between ∼0.013 and ∼0.044), the helical species and aggregated β-sheets (∼15-mer) coexist. However, the β-structure is stable and does not form larger aggregates. At Aβ:GM1 ratios above ∼0.044, the β-structure is converted to a second, seed-prone β-structure. The seed recruits monomers from the aqueous phase to form amyloid fibrils. These results will shed light on a molecular mechanism for the pathogenesis of the disease.

The abnormal deposition of amyloids by amyloid-β protein (Aβ) is a pathological hallmark of Alzheimer's disease (AD). Aged rodents rarely develop the characteristic lesions of the disease, which is different from the case in humans. Rodent Aβ (rAβ) differs from human Aβ (hAβ) only in the three substitutions of Arg to Gly, Tyr to Phe, and His to Arg at positions 5, 10, and 13, respectively. Understanding the reason why rodent Aβ does not form amyloids is important to revealing factors that cause the abnormal aggregation of Aβ under pathologic conditions. We have proposed that the binding of Aβ to membranes with ganglioside clusters plays an important role in the abnormal aggregation of Aβ. In this study, we compared hAβ and rAβ in terms of aggregation on neuronal cells, on raftlike model membranes, and in buffer. We found that rAβ formed amyloid fibrils similar to those of hAβ in buffer solution. In contrast, on cell membranes and raftlike membranes, hAβ formed toxic, mature amyloid fibrils, whereas rAβ produced less toxic protofibrils that were not stained by the amyloid-specific dye Congo red. Thus, our ganglioside cluster-mediated amyloidogenesis hypothesis explains the immunity of rodents from cerebral Aβ amyloid deposition, strengthening the importance of ganglioside clusters as a platform of abnormal Aβ deposition in the pathology of AD.

The microRNA miR-22 targets CDK6, SIRT1, and Sp1—genes involved in regulation of the senescence program—to suppress cell growth and proliferation., Cellular senescence acts as a barrier to cancer progression, and microRNAs (miRNAs) are thought to be potential senescence regulators. However, whether senescence-associated miRNAs (SA-miRNAs) contribute to tumor suppression remains unknown. Here, we report that miR-22, a novel SA-miRNA, has an impact on tumorigenesis. miR-22 is up-regulated in human senescent fibroblasts and epithelial cells but down-regulated in various cancer cell lines. miR-22 overexpression induces growth suppression and acquisition of a senescent phenotype in human normal and cancer cells. miR-22 knockdown in presenescent fibroblasts decreased cell size, and cells became more compact. miR-22–induced senescence also decreases cell motility and inhibits cell invasion in vitro. Synthetic miR-22 delivery suppresses tumor growth and metastasis in vivo by inducing cellular senescence in a mouse model of breast carcinoma. We confirmed that CDK6, SIRT1, and Sp1, genes involved in the senescence program, are direct targets of miR-22. Our study provides the first evidence that miR-22 restores the cellular senescence program in cancer cells and acts as a tumor suppressor.