Type I nitric oxide synthase (NOS) is the predominant NOS in rat small intestine. Regulation by platelet-activating factor

AbstractConstitutive nitric oxide synthase (cNOS) may play an important protective role in the intestine, since our previous study has shown that the degree of bowel injury induced by platelet-activating factor (PAF), a potent inflammatory mediator, is inversely related to the cNOS content of the intestine. This study aims to examine the composition of the cNOS system in rat small intestine, and its regulation by PAF. We found that an approximately 120 kDa NOS I (neuronal NOS) is the predominant NOS in rat intestine, as evidenced by the following: (a) immunoblotting with specific antibodies detected a NOS I of approximately 120 kDa, but little NOS III; (b) the Ca2+-dependent, constitutive NOS (cNOS) activity of the rat intestine was removed by immunoprecipitation with the anti-NOS I, but not anti-NOS II or anti-NOS III antibodies; (c) RT–PCR revealed constitutive expression of NOS I in the intestinal tissue, but only a minute amount of NOS III. Immunofluorescent staining with anti-NOS I located NOS in the Auerbach plexus and nerve fibers in the muscle layer. We also found that this 120 kDa NOS I is rapidly (within 1 h) down-regulated in response to PAF administration. The protein level, enzyme activity as well as mRNA of nNOS were all decreased in the intestine

Decision Theory-Based COI-SNP Tagging Approach for 126 Scombriformes Species Tagging

The mitochondrial gene cytochrome c oxidase I (COI) is commonly used for DNA barcoding in animals. However, most of the COI barcode nucleotides are conserved and sequences longer than about 650 base pairs increase the computational burden for species identification. To solve this problem, we propose a decision theory-based COI SNP tagging (DCST) approach that focuses on the discrimination of species using single nucleotide polymorphisms (SNPs) as the variable nucleotides of the sequences of a group of species. Using the example of 126 teleost mackerel fish species (order: Scombriformes), we identified 281 SNPs by alignment and trimming of their COI sequences. After decision rule making, 49 SNPs in 126 fish species were determined using the scoring system of the DCST approach. These COI-SNP barcodes were finally transformed into one-dimensional barcode images. Our proposed DCST approach simplifies the computational complexity and identifies the most effective and fewest SNPs to resolve or discriminate species for species tagging

Enhanced oxidative stress and the glycolytic switch in superficial urothelial carcinoma of urinary bladder

AbstractObjectiveTo examine whether oxidative stress and the glycolytic switch are correlated to tumor grading, tumor recurrence, and disease progression in urothelial carcinoma (UC) of the urinary bladder (UB).MethodsAll surgical specimens obtained from 27 patients (each containing their UC and normal tissues of UB) were subjected to a pathological examination by computerized tomography, and a portion of each specimen was used for the analysis of molecular biomarkers. The mRNA expression levels of pyruvate dehydrogenase kinase-1 (PDK1), hypoxia-inducible factor 1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase, and glucose transporter protein 1 (Glut-1) were measured using TaqMan-based real-time quantitative polymerase chain reaction. In addition, 8-hydroxy-2-deoxyguanosine (8-OHdG) and the mitochondrial DNA (mtDNA) copy number were also determined.ResultsThe 8-OHdG content and glycolytic genes expression were higher in UC of the UB than those in the normal tissues of UB, whereas the mtDNA copy number was depleted. According to the multivariate analysis, patients with Grade 3 tumors had higher expression levels of HIF-1α, LDHA, and Glut-1 than those with Grades 1 and 2 tumors. In addition, patients with locally recurrent tumors had a higher expression of HIF-1α and LDHA than those with nonrecurrent tumors. Furthermore, patients under disease progression had higher levels of HIF-1α and PDK1 than those not under disease progression.ConclusionsUC of the UB manifested that the glycolytic phenotype would reflect the Warburg effect. We suggest that the molecular mechanism in the regulation of glycolytic switch in UC of the UB might provide a specific biomarker for the future development of cancer diagnosis

Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report

Sarcomatoid hepatocellular carcinoma (HCC) is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (< 20 ng/mL) through the whole course of treatment. We considered sarcomatoid hepatocellular carcinoma bone metastasis a highly aggressive lesion with unusual metastatic pattern. Surgical treatment with adequate safe margin in such a huge tumor with hypervascularity and extensive invasion in the pelvis was difficult; and radiotherapy maybe refractory regarding the sarcomatous nature. Therefore, debulking operation with local symptoms control may provide a better quality of life. And the clinical course suggests sarcomatoid hepatocellular carcinoma is derived from the transition of an ordinary hepatocellular carcinoma

Delivery of chemotherapeutic agents using drug-loaded irradiated tumor cells to treat murine ovarian tumors

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the leading cause of death among women with gynecologic malignancies in the United States. Advanced ovarian cancers are difficult to cure with the current available chemotherapy, which has many associated systemic side effects. Doxorubicin is one such chemotherapeutic agent that can cause cardiotoxicity. Novel methods of delivering chemotherapy without significant side effects are therefore of critical need.</p> <p>Methods</p> <p>In the current study, we generated an irradiated tumor cell-based drug delivery system which uses irradiated tumor cells loaded with the chemotherapeutic drug, doxorubicin.</p> <p>Results</p> <p>We showed that incubation of murine ovarian cancer cells (MOSEC) with doxorubicin led to the intracellular uptake of the drug (MOSEC-dox cells) and the eventual death of the tumor cell. We then showed that doxorubicin loaded MOSEC-dox cells were able to deliver doxorubicin to MOSEC cells in vivo. Further characterization of the doxorubicin transfer revealed the involvement of cell contact. The irradiated form of the MOSEC-dox cells were capable of treating luciferase-expressing MOSEC tumor cells (MOSEC/luc) in C57BL/6 mice as well as in athymic nude mice resulting in improved survival compared to the non drug-loaded irradiated MOSEC cells. Furthermore, we showed that irradiated MOSEC-dox cells was more effective compared to an equivalent dose of doxorubicin in treating MOSEC/luc tumor-bearing mice.</p> <p>Conclusions</p> <p>Thus, the employment of drug-loaded irradiated tumor cells represents a potentially innovative approach for the delivery of chemotherapeutic drugs for the control of ovarian tumors.</p

RINGdb: An integrated database for G protein-coupled receptors and regulators of G protein signaling

BACKGROUND: Many marketed therapeutic agents have been developed to modulate the function of G protein-coupled receptors (GPCRs). The regulators of G-protein signaling (RGS proteins) are also being examined as potential drug targets. To facilitate clinical and pharmacological research, we have developed a novel integrated biological database called RINGdb to provide comprehensive and organized RGS protein and GPCR information. RESULTS: RINGdb contains information on mutations, tissue distributions, protein-protein interactions, diseases/disorders and other features, which has been automatically collected from the Internet and manually extracted from the literature. In addition, RINGdb offers various user-friendly query functions to answer different questions about RGS proteins and GPCRs such as their possible contribution to disease processes, the putative direct or indirect relationship between RGS proteins and GPCRs. RINGdb also integrates organized database cross-references to allow users direct access to detailed information. The database is now available at . CONCLUSION: RINGdb is the only integrated database on the Internet to provide comprehensive RGS protein and GPCR information. This knowledgebase will be useful for clinical research, drug discovery and GPCR signaling pathway research

Fluoroquinolone Resistance in Salmonella enterica Serotype Choleraesuis, Taiwan, 2000–2003

Salmonella enterica serotype Choleraesuis is a highly invasive pathogen that infects humans and causes systemic infections that require antimicrobial therapy. Surveillance in Taiwan showed that fluoroquinolone resistance in S. Choleraesuis markedly increased from 2000 to 2003, reaching approximately 70% in 2003

Ultrasmall all-optical plasmonic switch and its application to superresolution imaging

Because of their exceptional local-field enhancement and ultrasmall mode volume, plasmonic components can integrate photonics and electronics at nanoscale, and active control of plasmons is the key. However, all-optical modulation of plasmonic response with nanometer mode volume and unity modulation depth is still lacking. Here we show that scattering from a plasmonic nanoparticle, whose volume is smaller than 0.001 μm3, can be optically switched off with less than 100 μW power. Over 80% modulation depth is observed, and shows no degradation after repetitive switching. The spectral bandwidth approaches 100 nm. The underlying mechanism is suggested to be photothermal effects, and the effective single-particle nonlinearity reaches nearly 10−9 m2/W, which is to our knowledge the largest record of metallic materials to date. As a novel application, the non-bleaching and unlimitedly switchable scattering is used to enhance optical resolution to λ/5 (λ/9 after deconvolution), with 100-fold less intensity requirement compared to similar superresolution techniques. Our work not only opens up a new field of ultrasmall all-optical control based on scattering from a single nanoparticle, but also facilitates superresolution imaging for long-term observation