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1.
Nat Commun ; 8: 15070, 2017 04 19.
Article in English | MEDLINE | ID: mdl-28429712

ABSTRACT

Semiconductor compounds are widely used for photocatalytic hydrogen production applications, where photogenerated electron-hole pairs are exploited to induce catalysis. Recently, powders of a metallic oxide (Sr1-xNbO3, 0.03

2.
Animal ; 9(11): 1749-55, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26173627

ABSTRACT

The aim of this study was to evaluate the effects of geese's maternal diet supplemented with flaxseed on the fatty acid profiles of egg yolks and the antioxidant status of their offspring. A total of 288 female Huoyan geese (42 weeks old) were randomly allotted to four experimental groups in this 56-day experiment and fed on diets containing flaxseed at 0% (control), 5%, 10% and 15%, respectively. There were nine replicate pens per treatment, with eight geese per replicate pen. The concentration of α-linolenic acid (linear, P<0.01), EPA (20:5n-3; linear, P<0.01), DHA (22:6n-3; quadratic, P=0.03) and n-3 polyunsaturated fatty acid (PUFA) (linear, P<0.01) levels in the yolk lipids increased with increasing dietary flaxseed levels. Yolk palmitic acid (16:0, linear, P=0.05), saturated fatty acid (linear, P=0.04) level and total n-6/n-3 ratio (P<0.01) decreased in a linear fashion as dietary flaxseed levels increased. Increasing dietary flaxseed levels linearly decreased (P=0.01) the total cholesterol in egg yolks. After hatching, three 1-day-old gosling were selected randomly from each replicate to determine blood characteristics and liver antioxidant status. Aspartate aminotransferase activity (linear, P=0.03), total triglycerides (linear, P=0.02) and total cholesterol (linear, P=0.05) contents in blood linearly decreased as the levels of flaxseed increased. A linear dose response to maternal dietary flaxseed was detected for the activities of the goslings' liver enzymes catalase (linear, P=0.01), superoxide dismutase (linear, P<0.01) and glutathione peroxidase (linear, P<0.01). The malondialdehyde (quadratic, P=0.03) and alkaline phosphatase content in the livers of goslings decreased as flaxseed supplementation levels increased. In conclusion, the dietary addition of flaxseed up to 15%, in the maternal diet resulted in increased n-3 PUFA levels in egg yolks and improved the antioxidant status of offspring in a dose-dependent manner.


Subject(s)
Antioxidants/metabolism , Diet/veterinary , Dietary Supplements , Flax , Geese/physiology , Animals , Animals, Newborn , Antioxidants/analysis , Blood Chemical Analysis , Cholesterol/analysis , Dose-Response Relationship, Drug , Egg Yolk/chemistry , Fatty Acids/analysis , Fatty Acids, Omega-3/analysis , Fatty Acids, Unsaturated/analysis , Female , Liver/metabolism , Triglycerides/analysis , alpha-Linolenic Acid/analysis
3.
Cell Death Dis ; 5: e995, 2014 Jan 16.
Article in English | MEDLINE | ID: mdl-24434518

ABSTRACT

Ovarian cancer is the deadliest of gynecologic cancers, largely due to the development of drug resistance in chemotherapy. Prostasin may have an essential role in the oncogenesis. In this study, we show that prostasin is decreased in an ovarian cancer drug-resistant cell line and in ovarian cancer patients with high levels of excision repair cross-complementing 1, a marker for chemoresistance. Our cell cultural model investigation demonstrates prostasin has important roles in the development of drug resistance and cancer cell survival. Forced overexpression of prostasin in ovarian cancer cells greatly induces cell death (resulting in 99% cell death in a drug-resistant cell line and 100% cell death in other tested cell lines). In addition, the surviving cells grow at a much lower rate compared with non-overexpressed cells. In vivo studies indicate that forced overexpression of prostasin in drug-resistant cells greatly inhibits the growth of tumors and may partially reverse drug resistance. Our investigation of the molecular mechanisms suggests that prostasin may repress cancer cells and/or contribute to chemoresistance by modulating the CASP/P21-activated protein kinase (PAK2)-p34 pathway, and thereafter PAK2-p34/JNK/c-jun and PAK2-p34/mlck/actin signaling pathways. Thus, we introduce prostain as a potential target for treating/repressing some ovarian tumors and have begun to identify their relevant molecular targets in specific signaling pathways.


Subject(s)
Actins/metabolism , Caspases/metabolism , Ovarian Neoplasms/enzymology , Serine Endopeptidases/metabolism , p21-Activated Kinases/metabolism , Antineoplastic Agents/pharmacology , Caspases/genetics , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Serine Endopeptidases/genetics , Signal Transduction , Tumor Cells, Cultured , p21-Activated Kinases/genetics
4.
Cell Death Dis ; 5: e1407, 2014 Sep 04.
Article in English | MEDLINE | ID: mdl-25188517

ABSTRACT

Ovarian cancer is a leading cause of cancer death as diagnosis is frequently delayed to an advanced stage. Effective biomarkers and screening strategies for early detection are urgently needed. In the current study, we identify PSP94 as a key upstream factor in mediating prostasin (a protein previously reported to be overexpressed in ovarian cancer) signaling that regulates prostasin expression and action in ovarian cancer cells. PSP94 is overexpressed in ovarian cancer cell lines and patients, and is significantly correlated with prostasin levels. Signaling pathway analysis demonstrated that both PSP94 and prostasin, as potential upstream regulators of the Lin28b/Let-7 pathway, regulate Lin28b and its downstream partner Let-7 in ovarian cancer cells. Expression of PSP94 and prostasin show a strong correlation with the expression levels of Lin28b/Let-7 in ovarian cancer patients. Thus, PSP94/prostasin axis appears to be linked to the Lin28b/Let-7 loop, a well-known signaling mechanism in oncogenesis in general that is also altered in ovarian cancer. The findings suggest that PSP94 and PSP94/prostasin axis are key factors and potential therapeutic targets or early biomarkers for ovarian cancer.


Subject(s)
Ovarian Neoplasms/pathology , Prostatic Secretory Proteins/metabolism , Serine Endopeptidases/metabolism , Biomarkers, Tumor/blood , Cell Line, Tumor , Female , Humans , MicroRNAs/metabolism , Neoplasm Staging , Ovarian Neoplasms/metabolism , Prostatic Secretory Proteins/antagonists & inhibitors , Prostatic Secretory Proteins/genetics , RNA Interference , RNA, Small Interfering/metabolism , RNA-Binding Proteins/metabolism , Signal Transduction
5.
Oncogene ; 33(45): 5288-94, 2014 Nov 06.
Article in English | MEDLINE | ID: mdl-24186202

ABSTRACT

Tumor drug resistance remains a major challenge in the treatment of cancer. Here, we show that Prostatic secretory protein 94 (PSP94) levels are reduced in ovarian cancer patients with high levels of excision repair cross-complementing 1 (ERCC1), a marker for chemoresistance. We find that PSP94 is decreased in an ovarian cancer drug-resistant cell line, and plays an important role in the development of drug resistance in vitro. Our studies indicate that PSP94 can partially reverse drug resistance in mouse tumor models in vivo and that a PSP94 peptide derivative PCK3145 suppresses chemoresistant cancer cell and tumor growth in vitro and in vivo. Our investigation of the involved molecular mechanisms suggests that PSP94 may confer drug resistance by modulating the Lin28b/Let-7 signaling pathway. We introduce PSP94 and its peptide derivative PCK3145 as potential target to reverse chemoresistance in ovarian cancer and have begun to identify their relevant molecular targets in specific signaling pathways.


Subject(s)
Ovarian Neoplasms/drug therapy , Peptide Fragments/pharmacology , Prostatic Secretory Proteins/genetics , Prostatic Secretory Proteins/pharmacology , Tumor Burden/drug effects , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Endonucleases/genetics , Endonucleases/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoblotting , Mice , MicroRNAs/genetics , Models, Genetic , Ovarian Neoplasms/genetics , Ovarian Neoplasms/metabolism , Paclitaxel/pharmacology , Prostatic Secretory Proteins/metabolism , RNA Interference , RNA-Binding Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Xenograft Model Antitumor Assays
7.
J Protein Chem ; 16(1): 59-66, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9055208

ABSTRACT

A cellobiohydrolase (CBH) with a molecular mass of 66 kD was purified from Trichoderma pseudokiningii S-38. Papain digestion produced a 59- to 60-kD core domain with 54% of intact activity on crystalline cellulose and with full activity against soluble substrates. Digestion products also included two small peptides with molecular mass of about 3-4 kD, which are heavily glycosylated and difficult to purify; the mixed peptides displayed the capacity to disorganize the cellulose fiber. The sequencing results indicated that the intact enzyme had a blocked N-terminal and there was a 10-amino-acid sequence in the N-terminal of the core protein of Ser-Gly-Thr-Ala-Val-Thr-Cys-Leu-Ala-Asp. Fluorescence and circular dichroism properties indicated that the core protein has an independent conformation and is conformationally similar to intact enzyme, suggesting that the spectroscopic properties of the intact enzyme come from the core protein.


Subject(s)
Cellulase/chemistry , Cellulase/isolation & purification , Fungal Proteins/chemistry , Fungal Proteins/isolation & purification , Protein Conformation , Protein Structure, Tertiary , Trichoderma/enzymology , Amino Acid Sequence , Catalysis , Cellulase/metabolism , Cellulose 1,4-beta-Cellobiosidase , Circular Dichroism , Fungal Proteins/metabolism , Hydrolysis , Papain , Particle Size , Sequence Analysis , Spectrometry, Fluorescence
8.
J Biol Chem ; 272(6): 3190-4, 1997 Feb 07.
Article in English | MEDLINE | ID: mdl-9013553

ABSTRACT

The high resolution refined structures of 23 enzymes were analyzed to determine the properties of amino acids involved in active site regions. These regions were found to be rich in G-X-Y or Y-X-G oligopeptides, where X and Y are polar and non-polar residues, respectively, that are small and with low polarity. Other regions of the enzyme molecules have significantly fewer of these sequences. These features suggest that glycine residues may provide flexibility necessary for enzyme active sites to change conformation, and the G-X-Y or Y-X-G oligopeptides may be a motif for the formation of enzyme active sites.


Subject(s)
Enzymes/chemistry , Glycine , Models, Molecular , Amino Acid Sequence , Binding Sites , Crystallography, X-Ray , Molecular Sequence Data , Protein Conformation , Structure-Activity Relationship , Superoxide Dismutase/chemistry
9.
J Protein Chem ; 16(7): 681-8, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9330226

ABSTRACT

To gain further insight into the difference in substrate specificity between endoglucanase and cellobiohydrolase, the intrinsic fluorescence properties of cellobiohydrolase I (CBH I) and endoglucanase I (EG I) from Trichoderma pseudokiningii S-38 were investigated. The results for the spectral characteristics, ligand binding and fluorescence quenching suggest that the fluorescence of two enzymes comes from tryptophan residues, and that tryptophan residue(s) may be involved in the function of the two enzymes. The results also suggest that the binding tryptophan in EG I may be more exposed to solvent than that in CBH I. This interpretation is supported by the observations that the effects of pH upon the fluorescence of EG I are greater than that of CBH I; spectral shifts are different in EG I and CBH I under various conditions, and fluorescence lifetime changes caused by cellobiose binding are larger for EG I than for CBH I.


Subject(s)
Cellulase/chemistry , Fluorescence , Trichoderma/enzymology , Acrylamide , Acrylamides/pharmacology , Cellulase/metabolism , Cellulose 1,4-beta-Cellobiosidase , Hydrogen-Ion Concentration , Kinetics , Ligands , Potassium Iodide/pharmacology , Spectrometry, Fluorescence , Substrate Specificity , Tryptophan/chemistry , Tryptophan/metabolism
10.
Xenobiotica ; 33(12): 1261-71, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14765546

ABSTRACT

1. A sensitive liquid chromatographic-tandem mas spectrometric assay was developed and validated to determine the major metabolite of betahistine, 2-pyridylacetic acid, in human plasma. 2. The analyte was extracted from plasma samples by liquid-liquid extraction and analysed using liquid chromatography-tandem mass spectrometry with an electrospray ionization interface. The method has a lower limit of quantitation of 1 ng ml(-1) fir a 0.5-ml plasma aliquot. The intra- and interday precision (relative standard deviation), calculated from quality control (QC) samples, was less than 10%. Accuracy as determined from QC samples was within +/-7%. 3. The validated method was successfully applied to a pharmacokinetic study of betahistine in healthy volunteers. After oral administration of a single dose of 24 mg betahistine mesylate to 20 healthy Chinese male volunteers, Cmax was 339.4 ng ml(-1) (range 77.3-776.4 ng ml(-1)). The t(1/2) was 5.2 h (range 2.0(-1)-11.4h). The AUC(0-t) obtained was 1153.5 ng ml(-1) h (range 278.5-3150.8 ng ml(-1)). The disposition of the metabolite exhibited a marked interindividual variation. 4. The plasma concentrations of the parent drug were less than 0.5 ng ml(-1), suggesting that it undergoes almost complete first-pass metabolism. The reported two active metabolites were not detected in the plasma of any volunteer. Although there is no evidence that the major metabolite has pharmacological activity, the clinical importance of 2-pyridylacetic acid in humans should be reinvestigated.


Subject(s)
Acetates/blood , Betahistine/metabolism , Betahistine/pharmacokinetics , Chromatography, Liquid/methods , Mass Spectrometry/methods , Pyridines/blood , Acetates/metabolism , Administration, Oral , Adult , Betahistine/adverse effects , Betahistine/blood , Blood Specimen Collection/methods , Calibration , Chromatography, Liquid/standards , Humans , Linear Models , Male , Mass Spectrometry/standards , Pyridines/metabolism , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/methods
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