Publications by authors named "Liying Shi"

32 Publications

Effective diagnostic model construction based on discriminative breast ultrasound image regions using deep feature extraction.

Med Phys 2021 Mar 10. Epub 2021 Mar 10.

Department of Radiology, Affiliated Hospital of Guizhou Medical University, 28 Guiyi Road, Guiyang, China.

Purpose: This research aims to analyze the diagnostic contribution of different discriminative regions of the breast ultrasound image and develop a more effective diagnosis method taking advantage of the discriminative regions' complementarity.

Methods: First, the discriminative regions of the original breast ultrasound image as the inner region of the lesion, the marginal zone of the lesion, and the posterior echo region of the lesion were defined. The pretrained Inception-V3 network was used to analyze the diagnostic contribution of these discriminative regions. Then, the network was applied to extract the deep features of the original image and the other three discriminative region images. Since there are many features, principal components analysis (PCA) was used to reduce the dimensionality of the extracted deep features. The selected deep features from different discriminative regions were fused to original image features and sent to the stacking ensemble learning classifier for classification experiments. In this study, 479 cases of breast ultrasound images, including 356 benign lesions and 123 malignant ones, were collected retrospectively and randomly divided into the training and validation set.

Results: Experimental results show that by using Inception-V3, the diagnostic performance of each discriminative region is different, and the diagnostic accuracy and the area under the ROC curve (AUC) of the lesion marginal zone image (78.3%, 0.798) are higher than those of the lesion inner region image (73.3%, 0.763) and the posterior echo region image (71.7%, 0.688), but lower than those of the original image (80.0%, 0.817). Furthermore, the best classification performance was obtained when all the four types of deep features (from the original image and three discriminative region images) were fused, and the ensemble learning for classification evaluation was employed. Compared with the original image, the classification accuracy and AUC increased from 80.83%, 0.818 to 85.00%, 0.872, and the classification sensitivity and specificity varied from 0.710, 0.798 to 0.871, 0.787.

Conclusions: The inner region of the lesion, the marginal zone of the lesion, and the posterior echo region of the lesion play significant roles in the diagnosis of the breast ultrasound image. Deep feature fusion of these three kinds of images and the original image can effectively improve the accuracy of diagnosis.
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http://dx.doi.org/10.1002/mp.14832DOI Listing
March 2021

Thyroid imaging reporting and data system (TIRADS) for ultrasound features of nodules: multicentric retrospective study in China.

Endocrine 2021 Apr 27;72(1):157-170. Epub 2020 Aug 27.

Institute of Ultrasound in Medicine, The Affiliated Sichuan Provincial People's Hospital of Electronic Science and Technology University of China, Chengdu, 610071, China.

Purpose: To establish a practical and simplified Chinese thyroid imaging reporting and data system (C-TIRADS) based on the Chinese patient database.

Methods: A total of 2141 thyroid nodules that were neither cystic nor spongy were used in the current study. These specimens were derived from 2141 patients in 131 alliance hospitals of the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The ultrasound features, including location, orientation, margin, halo, composition, echogenicity, echotexture, echogenic foci and posterior features were assessed. Univariate and multivariate analyses were performed to investigate the association between ultrasound features and malignancy. The regression equation, the weighting, and the counting methods were used to determine the malignant risk of the thyroid nodules. The areas under the receiver operating characteristic curve (Az values) were calculated.

Results: Of the 2141 thyroid nodules, 1572 were benign, 565 were malignant, and 4 were borderline. Vertical orientation, ill-defined, or irregular margin (including extrathyroidal extension), microcalcifications, solid, and markedly hypoechoic were positively associated with malignancy, while comet-tail artifacts were negatively associated with malignancy. The logistic regression equation yielded the highest Az value of 0.913, which was significantly higher than that obtained using the weighting method (0.893) and the counting method (0.890); however, no significant difference was found between the latter two. The C-TIRADS, based on the counting method, was designed following the principle of balancing the diagnostic performance and sensitivity of the risk stratification with the ease of use.

Conclusions: A relatively simple C-TIRADS was established using the counting value of positive and negative ultrasound features.
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http://dx.doi.org/10.1007/s12020-020-02442-xDOI Listing
April 2021

In vitro Permeability and Bioavailability Enhancement of Curcumin by Nanoemulsion via Pulmonary Administration.

Curr Drug Deliv 2019 ;16(8):751-758

Department of Pharmaceutics, School of Pharmacy, Harbin Medical University, Harbin, 150086, China.

Background: Curcumin has shown considerable pharmacological activity, including antiinflammatory activity. Nevertheless, the pharmacological effect of curcumin may be limited because of poor water solubility, metabolizing rapidly and systemic elimination.

Objective: In the current research, a novel curcumin nanoemulsion (Cur-NE) was developed for improving in vitro permeability and bioavailability via pulmonary administration.

Methods: The Cur-NE was prepared by a modified emulsification-evaporation method and its surfac morphology, particles size and distribution, and encapsulation efficiencies of drug in NE were characterized. In vitro transmembrane transport experiment was performed to investigate the transport profile of curcumin across Xenopus alveolar membrane. The pharmacokinetics of Cur-NE in rabbits was evaluated.

Results: The average particles size, zeta potential, polydispersity index of Cur-NE were 234.8±1.08 nm, -19.5±0.2 mV and 0.10, respectively. Xenopus alveolar membrane was used in the transmembrane transport study, the cumulative amount of curcumin was 6.6% for curcumin suspensions, but nearly 50% for Cur-NE at the time of 8 h (P<0.05). The pharmacokinetic study in rabbits, the absolute bioavailability of curcumin for Cur-NE was 24.11%.

Conclusion: Thus, a novel Cur-NE for pulmonary drug delivery was developed for improving in vitro permeability and bioavailability, which can be an alternate to the oral administration.
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http://dx.doi.org/10.2174/1567201816666190717125622DOI Listing
May 2020

Association of a Gene Haplotype with Behcet's Disease in a Chinese Han Population.

Ocul Immunol Inflamm 2021 Feb 31;29(2):219-227. Epub 2019 Oct 31.

Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P.R. China.

: To investigate the association of gene polymorphisms with Behcet's disease (BD) and acute anterior uveitis (AAU) in a Chinese Han population.: We performed a case-control association study in 480 patients with BD, 1151 patients with AAU and 1440 healthy controls. Six single nucleotide polymorphisms (SNPs) of were genotyped, including rs4077515, rs11145769, rs59902911, rs9411205, rs4073153 and rs1135314.: None of the individual SNPs in the gene showed an association with either BD or AAU. Haplotype analysis revealed a significant decrease of the frequency of a gene haplotype CGCCA (rs4077515, rs11145769, rs59902911, rs9411205, rs4073153) in BD when compared to healthy controls (= 0.012, OR = 0.585, 95%CI = 0.409 ~ 0.837). Haplotype analysis did not show an association between and AAU.: This study shows that a five-SNP haplotype of the gene (CGCCA) may be a protective factor for BD with ocular involvement, but not for AAU.
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http://dx.doi.org/10.1080/09273948.2019.1677915DOI Listing
February 2021

Association of apoptosis genes in PDCD1 but not PDCD1LG2, FAS, and FASLG with pediatric idiopathic uveitis in Han Chinese.

Pediatr Res 2020 03 16;87(4):634-638. Epub 2019 Oct 16.

Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China.

Background: Previous studies have shown that aberrant T lymphocyte apoptosis is involved in the pathogenesis of uveitis. Genetic variants of apoptotic pathway-related factors (including PDCD1, PDCD1LG2, FAS, and FASLG) may affect apoptosis and in turn predict susceptibility to autoimmune disease. This has not yet been studied in pediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis (JIA)-associated uveitis and was therefore the subject of the study presented here.

Methods: Fourteen single-nucleotide polymorphisms (SNPs) of several apoptosis-related pathway genes were analyzed in 1238 PIU patients, 128 JIA-associated uveitis patients and 1114 healthy controls using the iPLEX Gold Assay and MassARRAY platform.

Results: A lower frequency of the PDCD1/rs6710479 CC genotype in PIU patients was found when compared to controls (Pc = 3.42 × 10). A higher frequency of the PDCD1/rs7421861 A allele (Pc = 4.85 × 10) was observed in PIU patients as compared with controls. Stratification analysis showed a positive association of band keratopathy with the PDCD1/rs7565639 CT genotype (Pc = 1.05 × 10) and a negative association of this parameter with the PDCD1/rs7565639 C allele (Pc = 3.76 × 10).

Conclusions: This study revealed that rs6710479 and rs7421861 in the PDCD1 gene confer susceptibility to PIU in Han Chinese. A stratified analysis showed that PDCD1/rs7565639 is associated with band keratopathy in PIU patients.
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http://dx.doi.org/10.1038/s41390-019-0612-4DOI Listing
March 2020

Association of TLR2 Gene Polymorphisms with Presumed Viral-Induced Anterior Uveitis in male Han Chinese.

Exp Eye Res 2019 10 26;187:107777. Epub 2019 Aug 26.

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China; The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China. Electronic address:

The purpose of this study was to investigate whether single nucleotide polymorphisms (SNPs) of TLR2, TLR3, TLR4 and TLR9 genes are associated with susceptibility to presumed viral-induced anterior uveitis (PVIAU) and Posner-Schlossman syndrome (PSS). A case-control study was performed in 205 PVIAU patients and 1007 healthy controls. A total of 15 SNPs were genotyped by MassARRAY platform and iPLEX Gold Assay. Data were analyzed using a Chi-square (χ) test and Fisher's exact calibration test. Two hundred and three PSS patients served as an extra control to investigate whether there were similar genetic factors between PVIAU and PSS in the context of these tested SNPs in TLR genes. The results showed that the frequency of TLR2/rs7656411 GG genotype and G allele were significantly higher in PVIAU patients as compared with healthy controls (P = 1.10 × 10, corrected P value [Pc] = 4.93 × 10, odds ratio [OR] = 1.848; P = 3.57 × 10, Pc = 1.07 × 10, OR = 1.478, respectively). Gender stratification analysis showed a significantly increased frequency of the G allele in male patients (P = 7.46 × 10, Pc = 2.24 × 10, OR = 1.894). A weak correlation was found between two SNPs (rs3804100 and rs5743705) of the TLR2 gene with PSS. However, after Bonferroni correction, statistical significance was lost. This study shows that the polymorphisms of TLR2/rs7656411 are positively associated with PVIAU in male Chinese patients. PVIAU and PSS have a different genetic background in the context of the tested SNPs.
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http://dx.doi.org/10.1016/j.exer.2019.107777DOI Listing
October 2019

Anticancer effect of inactivated Sendai virus strain Tianjin on human osteosarcoma HOS cells.

Gen Physiol Biophys 2019 Jul 20;38(4):335-342. Epub 2019 Jun 20.

Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

Ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) has been proved to have antitumor effects in many kinds of tumor cells. Here, we investigated the anticancer properties of UV-Tianjin on human osteosarcoma HOS cells and the underlying molecular mechanism. Apoptosis, intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential were determined by flow cytometry analysis. The expression levels of apoptosis-related proteins were tested by western blotting. The results showed that UV-Tianjin concentration-dependently induced apoptosis in HOS cells. UV-Tianjin-induced apoptosis was mediated by the mitochondrial pathway, which was confirmed by mitochondrial dysfunction, downregulation of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-xL (Bcl-xL) and myeloid cell leukemia-1 (Mcl-1), upregulation of B-cell lymphoma 2 associated X protein (Bax) and Bcl-2 Homologous Antagonist/Killer (Bak), as well as the cleavage of caspase-9 and -3. Further analysis showed that UV-Tianjin augmented the phosphorylation of c-Jun N-terminal kinase, the extracellular-regulated kinase and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, as well as the generation of ROS. Moreover, UV-Tianjin-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor. Taken together, our results indicated that UV-Tianjin exerts antitumor effects by inducing mitochondria-dependent apoptosis involving ROS generation and MAPK pathway in human osteosarcoma HOS cells.
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http://dx.doi.org/10.4149/gpb_2019015DOI Listing
July 2019

Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion.

Emerg Microbes Infect 2019 ;8(1):448-460

a Institute of Cell Biology , Zhejiang University School of Medicine , Hangzhou , People's Republic of China.

Rapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing Mycobacterium tuberculosis, the pathological significance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were significantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome-lysosome fusion in macrophages. Further investigations showed that VPS33A was the direct target of miR-423-5p, and the two CUGCCCCUC domains in VPS33A 3'-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between VPS33A and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our findings suggests that miR-423-5p could suppress autophagosome-lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis.
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http://dx.doi.org/10.1080/22221751.2019.1590129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455132PMC
August 2019

The Elevated ASK1 Expression Inhibits Proliferation and Invasion in Gastric Cancer HGC-27 Cells.

Anat Rec (Hoboken) 2018 11 15;301(11):1815-1819. Epub 2018 Oct 15.

Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, 310013, People's Republic of China.

This study aimed to evaluate the effects and mechanism of action of ASK1 gene on the growth and migration of gastric cancer (GC) cells. Total RNA was extracted from the gastric cell lines and GC tissues. The expression level of ASK1, and the association between ASK1 expression and clinicopathological characteristics was assessed by real-time polymerase chain reaction. The effects of ASK1 on the proliferation of HGC-27 cells were assessed by the CCK-8 assay. In addition, the effects of ASK1 on the migration of HGC-27 cells were analyzed by the migration assay using transwell chambers. The expression levels of signaling proteins related to cell migration were detected by Western blotting. Although no significant differences were observed in the expression levels of ASK1 between the GC tissue samples and the normal tissue samples (P = 0.241), ASK1 expression correlated with tumor lymph node metastasis (P = 0.008). Furthermore, ASK1 inhibited proliferation and migration of HGC-27 cells. The increase in the expression of ASK1 in HGC-27 cells induced the activation of the JNK and p38 signaling pathways. The findings demonstrated that increased ASK1 expression level inhibited migration and proliferation of HGC-27 gastric cancer cells, whereas the possible mechanism of action may be attributed to the activation of the JNK and p38 signaling pathways. Anat Rec, 301:1815-1819, 2018. © 2018 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ar.23906DOI Listing
November 2018

Inactivated Sendai virus strain Tianjin induces apoptosis and autophagy through reactive oxygen species production in osteosarcoma MG-63 cells.

J Cell Physiol 2019 04 26;234(4):4179-4190. Epub 2018 Aug 26.

Department of Pathogenic Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

Sendai virus strain Tianjin, a novel genotype of Sendai virus, has been proven to possess potent antitumor effect on certain cancer cell types although inactivated by ultraviolet (UV). This study was carried out to investigate the in vitro anticancer properties of UV-inactivated Sendai virus strain Tianjin (UV-Tianjin) on human osteosarcoma cells and the underlying molecular mechanism. Our studies demonstrated UV-Tianjin significantly inhibited the viability of human osteosarcoma cell lines and triggered apoptosis through activation of both extrinsic and intrinsic pathways in MG-63 cells. Meanwhile, autophagy occurred in UV-Tianjin-treated cells. Blockade of autophagy with 3-methyladenine remarkably attenuated the inhibition of cell proliferation by UV-Tianjin, suggesting that UV-Tianjin-induced autophagy may be contributing to cell death. Furthermore, UV-Tianjin induced reactive oxygen species (ROS) production, which was involved in the execution of MG-63 cell apoptosis and autophagy, as evidenced by the result that treatment of N-acetyl-L-cysteine, a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of apoptosis promoted autophagy, whereas suppression of autophagy attenuated apoptosis. Our results suggest that UV-Tianjin triggers apoptosis and autophagic cell death via generation of the ROS in MG-63 cells, which might provide important insights into the effectiveness of novel strategies for osteosarcoma therapy.
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http://dx.doi.org/10.1002/jcp.27176DOI Listing
April 2019

Regulatory Roles of Osteopontin in Production of Monocyte-Origin MCP-1.

Cell Transplant 2018 08 12;27(8):1185-1194. Epub 2018 Jul 12.

1 Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Osteopontin (OPN), expressed by various immune cells, plays a critical role in leukocyte migration. Although OPN was found to selectively induce the expression of proinflammatory chemokines, the molecular mechanisms that control OPN gene expression and its underlying mechanism for migration and recruitment of inflammatory cells remain largely unknown. In this study, real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine OPN and monocyte chemoattractant protein 1 (MCP-1) expression. Signaling and molecular events between OPN and MCP-1 were analyzed by Western blot. Leukocyte migration in the presence of OPN was measured by chemotaxis assay. Our data indicated that phosphoinositide 3-kinase (PI3K), c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) that are activated upon stimulation with lipopolysaccharide were shown to upregulate OPN expression. Endogenous production of OPN was attributable to increased production of MCP-1, and this effect could be blocked by an anti-β1 integrin antibody and JNK and p38 kinase inhibitors. Furthermore, we found that the effect of OPN on inflammatory cell migration was mediated through inducing the expression of MCP-1 in monocytes. These results support a role of OPN in monocyte migration via MCP-1, which may represent an additional mechanism for innate and adaptive immune responses.
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http://dx.doi.org/10.1177/0963689718756070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434466PMC
August 2018

The natural phenolic peperobtusin A induces apoptosis of lymphoma U937 cells via the Caspase dependent and p38 MAPK signaling pathways.

Biomed Pharmacother 2018 Jun 5;102:772-781. Epub 2018 Apr 5.

The School of Life Science and Biotechnology, Dalian University, Dalian, 116622, PR China. Electronic address:

Our previous research found the ethyl acetate extract of Peperomia tetraphylla (EAEPT) inhibited the growth of U937 cells by blocking the cell cycle and prompted apoptosis via the reactive oxygen species (ROS)-medicated mitochondria pathway. While the compounds in EAEPT which possessed the anti-tumor activity were unclear. Peperobtusin A is a phenolic compound, which was isolated from the whole plant of Peperomia tetraphylla. In this work, we found that peperobtusin A had the anti-proliferative effects against human lymphoma U937 cells and induced apoptosis in a dose dependent manner. Peperobtusin A significantly enhanced the formation of intracellular ROS and induced the loss of mitochondrial membrane potential (Δψm). And peperobtusin A could increase the ratio of Bax/Bcl-2, induce the cleavage of Bid, Caspase-3, Caspase-8 and Caspase-9 and enhance the level of P-P38. Moreover, peperobtusin A induced the accumulation of cells at S phase. Through using of inhibitors such as antioxidant NAC, pan-caspase inhibitor Z-VAD-FMK, p38 MAPK specific inhibitor SB203580, we found that intracellular ROS generation, activation of Caspases and p38 MAPK played very important roles in the apoptosis induced by peperobtusin A in U937 cells. Our results indicated that intracellular ROS generation, the Caspase-dependent and p38 MAPK signaling pathways involved in apoptosis induced by peperobtusin A in U937 cells.
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http://dx.doi.org/10.1016/j.biopha.2018.03.141DOI Listing
June 2018

Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis.

Authors:
Zhe Han Liying Shi

Biochem Biophys Res Commun 2018 01 21;495(1):947-953. Epub 2017 Nov 21.

Department of Microbiology, Basic Medical College, Tianjin Medical University, No. 22, Qixiangtai Road, Heping District, Tianjin 300070, China. Electronic address:

Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay reveled that miR-200c both targeted the 3'-UTR of LUCAT1 and ABCB1 mRNA, suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma proliferation, invasion and methotrexate resistance. Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.
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http://dx.doi.org/10.1016/j.bbrc.2017.11.121DOI Listing
January 2018

Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists.

J Med Chem 2017 01 28;60(1):362-372. Epub 2016 Dec 28.

Biochemical Technologies, Science and Technology Division, Corning , New York 14831, United States.

A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.
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http://dx.doi.org/10.1021/acs.jmedchem.6b01431DOI Listing
January 2017

Ethyl acetate extract of Peperomia tetraphylla induces cytotoxicity, cell cycle arrest, and apoptosis in lymphoma U937 cells.

Biomed Pharmacother 2016 Dec 12;84:1802-1809. Epub 2016 Nov 12.

The School of Life Science and Biotechnology, Dalian University, Dalian 116622, PR China. Electronic address:

The current study evaluated the cytotoxicity and the mechanism of apoptotic induction by Peperomia tetraphylla in U937 lymphoma cells. The results showed that P. tetraphylla ethyl acetate extract (EAEPT) inhibited the cell growth in U937 cells by MTT assay. After the U937 cells were treated with EAEPT, the cells exhibited marked morphological features of apoptosis (Hoechst 33342 staining) and the number of apoptotic cell (Annexin V-FITC/PI staining) increased. The treatment of EAEPT could induce loss of mitochondrial membrane potential (MMP) and increase the ROS level. Moreover, EAEPT treatment resulted in the accumulation of cells at S phase. We found that EAEPT could induce the cleavage of the caspase 3, caspase 8, caspase 9 and Bid. And the treatment of EAEPT could increase expression of Bax and down-regulate the expression of CCNB1, CCND1 and CDK1. The sub-fraction of EAEPT, namely EASub1 demonstrated the highest cytotoxicity activity on U937 cells. It was confirmed that EAEPT could inhibit the growth of U937 cells by blocking the cell cycle and prompted apoptosis via the ROS-medicated mitochondria pathway in vitro.
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http://dx.doi.org/10.1016/j.biopha.2016.10.092DOI Listing
December 2016

Inactivated Tianjin strain, a novel genotype of Sendai virus, induces apoptosis in HeLa, NCI-H446 and Hep3B cells.

Oncol Lett 2016 Jul 13;12(1):49-56. Epub 2016 May 13.

Department of Microbiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, P.R. China.

The Sendai virus strain Tianjin is a novel genotype of the Sendai virus. In previous studies, ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) demonstrated antitumor effects on human breast cancer cells. The aim of the present study was to investigate the antitumor effects of UV-Tianjin on the human cervical carcinoma HeLa, human small cell lung cancer NCI-H446 and human hepatocellular carcinoma Hep 3B cell lines, and the possible underlying mechanisms of these antitumor effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that UV-Tianjin treatment inhibited the proliferation of HeLa, NCI-H446 and Hep 3B cells in a dose- and time-dependent manner. Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide double staining indicated that UV-Tianjin induced dose-dependent apoptosis in all three cell lines with the most significant effect observed in the HeLa cell line. In the HeLa cell line, UV-Tianjin-induced apoptosis was further confirmed by the disruption of the mitochondria membrane potential and the activation of caspases, as demonstrated by fluorescent cationic dye and colorimetric assays, respectively. In addition, western blot analysis revealed that UV-Tianjin treatment resulted in significant upregulation of cytochrome , apoptosis protease activating factor-1, Fas, Fas ligand and Fas-associated protein with death domain, and activated caspase-9, -8 and -3 in HeLa cells. Based on these results, it is hypothesized that UV-Tianjin exhibits anticancer activity in HeLa, NCI-H446 and Hep 3B cell lines via the induction of apoptosis. In conclusion, the results of the present study indicate that in the HeLa cell line, intrinsic and extrinsic apoptotic pathways may be involved in UV-Tianjin-induced apoptosis.
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http://dx.doi.org/10.3892/ol.2016.4570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907004PMC
July 2016

Label-free cell phenotypic profiling and pathway deconvolution of neurotensin receptor-1.

Pharmacol Res 2016 06 23;108:39-45. Epub 2016 Apr 23.

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China. Electronic address:

Neurotensin (NT), an endogenous peptide found in the central nervous system and in peripheral tissues, contributes to the pathophysiology of neurodegenerative and psychiatric diseases, cancer, inflammation, and immunomodulatory disease. NT exerts its physiological effects predominantly through its cognate high-affinity neurotensin receptor-1 (NTS1). NTS1 emerges as a druggable target; however, there are limited numbers of NTS1 active compounds reported to date. Here we reported a label-free cell phenotypic profiling model for screening NTS1 ligands and differentiating their biased agonism. Resonant waveguide grating enabled dynamic mass redistribution (DMR) assay was first optimized against cell confluency and then used to characterize the endogenous NTS1 in HT-29 cell using known agonists and antagonists. Pathway modulators were also used to deconvolute the signaling pathways of endogenous NTS1. Results showed that the NTS1 DMR assay is robust for screening and can differentiate biased agonism; and the activation of NTS1 in HT-29 triggers multiple pathways including G signaling and epidermal growth factor receptor transactivation. This study highlighted the power of label-free DMR assay to characterize receptor signaling and pharmacology of distinct classes of ligands for NTS1, G protein-coupled receptors in general.
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http://dx.doi.org/10.1016/j.phrs.2016.04.018DOI Listing
June 2016

Anti-gastric cancer activity in three-dimensional tumor spheroids of bufadienolides.

Sci Rep 2016 Apr 21;6:24772. Epub 2016 Apr 21.

Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

Multicellular spheroids of cancer cells have been increasingly used to screen anti-tumor compounds, owing to their in vivo like microenvironment and structure as well as compatibility to high-throughput/high-content screening. Here we report the potency and efficacy of a family of bufadienolides to inhibit the growth of gastric cancer cell line HGC-27 in three-dimensional (3D) spheroidal models. Examining the morphological and growth patterns of several cell lines in round-bottomed ultra-low attachment microplate suggested that HGC-27 cells formed reproducibly multicellular spheroidal structures. Profiling of 15 natural bufadienolides isolated from toad skin indicated that 8 14-hydroxy bufadienolides displayed inhibitory activity of the growth of HGC-27 spheroids in a dose-dependent manner. Notably, compared to clinical drugs taxol and epirubicin, active bufadienolides were found to penetrate more effectively into the HGC-27 spheroids, but with a narrower effective concentration range and a shorter lasting inhibitory effect. Furthermore, compared to two-dimensional (2D) cell monolayer assays, active bufadienolides exhibited weaker efficacy and different potency in 3D spheroid model, demonstrating the great potential of 3D multicellular cell spheroid models in anti-cancer drug discovery and development.
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http://dx.doi.org/10.1038/srep24772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838868PMC
April 2016

Molecularly imprinted polymers based on SBA-15 for selective solid-phase extraction of baicalein from plasma samples.

Anal Bioanal Chem 2015 Jan 14;407(2):509-19. Epub 2014 Nov 14.

School of Pharmacy, Nanjing Medical University, Nanjing, 210029, China.

Highly selective molecularly imprinted mesoporous silica polymer ([email protected]) for baicalein (BAI) extraction was synthesized using a surface molecular imprinting technique on the SBA-15 supporter. Computational simulation was used to predict the optimal functional monomer for the rational design of [email protected] Meanwhile, high adsorption capacity was obtained when a suitable yield of molecularly imprinted polymers (MIPs) layer was grafted onto the surface of SBA-15. Characterization and performance tests of the obtained polymer revealed that [email protected] possessed a highly ordered mesoporous structure, reached saturated adsorption within 60 min, and exhibited higher sorption capacity to the target molecule BAI compared with non-imprinted mesoporous silica polymer ([email protected]) and SBA-15. Finally, [email protected] was successfully applied to solid-phase extraction (SPE) coupled with high-performance liquid chromatography and ultraviolet detection (HPLC-UV) for the determination of trace BAI in plasma samples. Mean recoveries of BAI through the molecularly imprinted solid-phase extraction (MISPE) sorbent, non-imprinted solid-phase extraction (NISPE) sorbent, and SBA-15 solid-phase extraction (SBA-15-SPE) sorbent were 94.4, 22.7, and 10.7 %, respectively, and the relative standard deviations were 2.9, 2.6, and 3.6 %, respectively. These results reveal that [email protected] as a SPE sorbent has good applicability to selectively separate and enrich trace BAI from complex samples.
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http://dx.doi.org/10.1007/s00216-014-8285-7DOI Listing
January 2015

[Anti-tumor effect of Sendai virus Tianjin strain defective interfering particles on tumor-bearing mice].

Zhonghua Zhong Liu Za Zhi 2014 Mar;36(3):177-82

Department of Microbiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.

Objective: To explore the anti-tumor effect and its mechanism of Sendai virus Tianjin strain defective interfering particles (DIP) on mouse models of colon carcinoma.

Methods: CT26 cells (5×10(6)/0.1 ml) were subcutaneously injected into the back of Bal B/c mice to establish murine colon carcinoma model. After the tumors reached 5 mm in diameter, the mice were randomly divided into Tianjin strain DIP group and saline control group. The former was intratumorally injected with Tianjin strain DIP (0.1 ml) once a day on day 4, 7, 10 and 13 after CT26 cell inoculation. The latter was intratumorally injected with the same volume of saline. Tumor volume and survival rate of the mice were calculated to confirm the anti-tumor effect of DIP. Flow cytometry and ELISA were used to examine the maturation and release of cytokines IL-6, IFN-α and TNF-α from murine myeloid dendritic cells (DCs) induced by Tianjin strain DIP. Moreover, real-time RT-PCR and immunohistochemistry were performed to identify whether the Tianjin strain DIP could induce infiltration of CD11c(+) DCs, CD4(+) and CD8(+) T cells in the tumors.

Results: On day 22 after CT26 cell inoculation, the average tumor volume of the Tianjin strain DIP group was (33.2 ± 2.0) mm(3), significantly smaller than that of the control group [(2 376.0 ± 130.8)mm(3), P < 0.01]. On day 50 after CT26 cell inoculation, the survival rate of mice was 90.0% in the Tianjin strain DIP group, much higher than that of the control group (30.0%, P < 0.01). Flow cytometry analysis showed that the expression of markers of DCs maturation, including CD40, CD80 and CD86, was dose-dependently increased by DIP or intact virus. No statistically significant difference was found betweent the DIP and intact virus groups. ELISA results showed that DIP could stimulate the secretion of IL-6, IFN-α and TNF-α from mouse DCs. The secretion of all of the cytokines was dose-dependently increased by DIP or intact virus. Real-time RT-PCR revealed that the expression of CD4, CD8 and CD11c mRNAs was increased in tumors treated with DIP compared with that of the saline group at all time points. Moreover, the expression level of all of them remained maximal at 120 h after the last treatment. Immunohistochemical staining revealed that the ratios of CD4(+), CD8(+) T cells or CD11c(+) DCs to total cells were (21.60 ± 1.49)%, (22.12 ± 2.84)% and (23.05 ± 2.91)%, respectively, in the DIP-treated tumors. In the tumors treated by saline, the ratios were (2.62 ± 0.60)%, (4.05 ± 0.12)% and (3.10 ± 0.09)%, respectively. The difference between experimental group and control group had statistical significance.

Conclusions: Tianjin strain DIP may exert anti-tumor effect on tumor-bearing mice. The mechanism is related with the antitumor immunity induced by DCs and T cells.
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March 2014

Inactivated Sendai virus strain Tianjin, a novel genotype of Sendai virus, inhibits growth of murine colon carcinoma through inducing immune responses and apoptosis.

J Transl Med 2013 Sep 5;11:205. Epub 2013 Sep 5.

Department of Microbiology, Basic Medical College, Tianjin Medical University, Tianjin 300070, China.

Background: Ultraviolet-inactivated, replication-defective Sendai virus particles (Z strain) have displayed antitumor effect through enhancing the immune responses or inducing apoptosis in a variety of carcinomas. Sendai virus strain Tianjin was isolated from the lungs of marmoset and proved to be a novel genotype of Sendai virus. In this study, we explored the antitumor effect and its mechanism of ultraviolet-inactivated, replication-defective Sendai virus strain Tianjin (UV-Tianjin) in mice bearing CT26 colon carcinoma.

Methods: Three injections of UV-Tianjin were delivered into CT26 tumors growing on the back of BALB/c mice. Tumor size was measured in a blinded manner and survival rate of mice was calculated. In order to make clear antitumor mechanism of UV-Tianjin, the maturation and interleukin-6 (IL-6) release from murine myeloid dendritic cells (DCs) was examined by flow cytometry or ELISA assay after induced by UV-Tianjin and compared with those of live virus. Moreover, real-time RT-PCR and immunohistochemistry was performed to identify whether UV-Tianjin could induce infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay was done to observe the apoptosis of CT26 tumor cells after UV-Tianjin injection.

Results: In animal model, UV-Tianjin could obviously inhibit the growth of CT26 tumors and prolong the survival of the tumor-bearing mice compared with control group (P < 0.01). In vitro murine DCs stimulated by UV-Tianjin underwent dose-dependent maturation, similar to that elicited by live virus. And the secretion amount of IL-6 from DCs induced by UV-Tianjin was a little lower than that released in the presence of live virus. Real-time RT-PCR and immunohistochemistry revealed that UV-Tianjin induced a remarkable infiltration of DCs, CD4⁺ and CD8⁺ T cells into tumors. The TUNEL assay showed that the apoptosis index of tumor tissues injected with UV-Tianjin was significantly higher than that of control group (P < 0.01).

Conclusions: Our results have demonstrated that UV-Tianjin alone could inhibit the growth of CT26 tumor in mice through enhancing host antitumor immunity and inducing apoptosis of tumor cells. Therefore, UV-Tianjin shows its prospect as a novel drug for carcinoma therapy.
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http://dx.doi.org/10.1186/1479-5876-11-205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844535PMC
September 2013

Two novel potent α-amylase inhibitors from the family of acarviostatins isolated from the culture of Streptomyces coelicoflavus ZG0656.

Chem Biodivers 2013 Mar;10(3):452-9

Tianjin State Laboratory of Cellular and Molecular Immunology, Department of Microbiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, PR China.

Two novel aminooligosaccharides were separated from the culture filtrate of Streptomyces coelicoflavus ZG0656. Their chemical structures were determined by acidic hydrolysis, electrospray-ionization tandem mass spectrometry (ESI-MS/MS), and NMR spectroscopy. The compounds were named acarviostatins III0(-1) and III23 according to the nomenclature of this group of metabolites. The two novel acarviostatins were both mixed noncompetitive inhibitors of porcine pancreatic α-amylase (PPA). The inhibition constants (K(i)) for acarviostatins III0(-1) and III23 were 0.009 and 0.026 μM, respectively, 151 and 52 times more potent than acarbose.
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http://dx.doi.org/10.1002/cbdv.201100451DOI Listing
March 2013

[Individualized partial laryngectomy during surgery of epiglottic carcinoma].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2012 Dec;26(24):1105-7

Department of Otolaryngology Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate an individualized operative modality of partial laryngectomy for suprahyoid epiglottis centered epiglottic carcinoma.

Method: Eleven cases of epiglottic squamous carcinoma which primarily focused in the suprahyoid region were included. Preoperative CT indicated that obvious margin with low density existed in the pre-epiglottic space in 3 cases, and pre-epiglottic space were involved in 8 cases, among which the arytenoid region were involved in 2 cases. An individualized partial laryngectomy was manipulated beyond the safe margin, an arytenoid epiglottic fold-plasty was performed and the remaining epiglottis was fixed to the tongue base. Adjuvant postoperative radiotherapy and chemotherapy were applied to all patients and the follow-up time lasted from 1 to 6 years with mean time of 3 years and 6 months.

Result: One patient died of recurrence in the tongue base after one year postoperatively, one was lost to follow-up 2 years after surgery. The overall 3-year survival rate was 81.8%. Nine patients were free from tracheal cannulation within one year postoperatively and the other two patients went on with tracheal tube assisted respiration. Aspiration gradually disappeared within 1-3 months.

Conclusion: Individualized partial laryngectomy in treatment of epiglottic carcinoma could preserve more laryngeal tissue and result in better laryngeal function preservation.
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December 2012

Berberine protects human renal proximal tubular cells from hypoxia/reoxygenation injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways.

J Transl Med 2013 Jan 29;11:24. Epub 2013 Jan 29.

Department of Anesthesiology, Tianjin First Center Hospital, Tianjin 300192, China.

Background: Ischemia/reperfusion injury plays a crucial role in renal transplantation, and represents a significant risk factor for acute renal failure and delayed graft function. The pathophysiological contribution of endoplasmic reticulum and mitochondria stress to ischemia/reperfusion injury has also been highlighted. Berberine (BBR) has been showed to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The study was carried out to investigate whether the pretreatment of BBR could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting mitochondria stress and endoplasmic reticulum stress pathways.

Methods: The cultured human renal proximal tubular cell line HK-2 cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 3 h reoxygenation (5% CO2, 21% O2, 74% N2). And BBR was added to the culture medium 2h prior to the treatment. Then the cell viability, oxidative stress level, morphological change of apoptosis and apoptotic rate were determined. In addition, Western blot analysis was performed to identify the expression of apoptotic pathway parameters, including Bcl-2, Bax and cytochrome C involved in mitochondrial-dependent pathway and ER stress hallmarks such as glucose-regulated protein 78 and CCAAT/enhancer binding protein homologous protein.

Results: H/R produced dramatic injuries in HK-2 cells. The cell viability and the oxidative stress level in group H/R was significantly decreased. The classical morphological change of apoptosis was found, while the apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased (p<0.05). Administration of BBR significantly inhibited these H/R induced changes (p<0.05).

Conclusion: This study revealed that BBR pretreatment serves a protective role against H/R induced apoptosis of human renal proximal tubular cells, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress pathways.
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http://dx.doi.org/10.1186/1479-5876-11-24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599611PMC
January 2013

Rational design of core-shell molecularly imprinted polymer based on computational simulation and Doehlert experimental optimization: application to the separation of tanshinone IIA from Salvia miltiorrhiza Bunge.

Anal Bioanal Chem 2012 Jul 11;403(9):2691-703. Epub 2012 May 11.

School of Pharmacy, Nanjing Medical University, Nanjing, China.

Computational simulation and Doehlert experimental optimization were done for the rational design of a core-shell molecularly imprinted polymer (CS-MIP) for use in the highly selective separation of Tanshinone IIA (TSIIA) from the crude extracts of Salvia miltiorrhiza Bunge (SMB). The functional monomer layer of the polymer shells directed the selective occurrence of imprinting polymerization at the surface of silica through the copolymerization of vinyl end groups with functional monomers and also drove TSIIA templates into the formed polymer shells through the charge-transfer complex interactions between TSIIA and the functional monomer layer. As a result, the maximum rebinding capacity was achieved with the use of optimal grafting ratio by the Doehlert design. The CS-MIP exhibited high recognition selectivity and binding affinity to TSIIA. When the imprinted particles were used as dispersive solid phase extraction sorbents, the recovery yield of TSIIA reached 93% by a one-step extraction from the crude extracts of SMB, and the purity of TSIIA was larger than 98% by HPLC analysis. These results show the possibility of a highly selective separation and enrichment of TSIIA from the SMB using the TSIIA-imprinted core-shell molecularly imprinted polymers.
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http://dx.doi.org/10.1007/s00216-012-6078-4DOI Listing
July 2012

New bibenzyl glycosides from leaves of Camellia oleifera Abel. with cytotoxic activities.

Fitoterapia 2011 Apr 8;82(3):481-4. Epub 2011 Jan 8.

College of Bioengineering, Dalian University, Dalian, China.

Studies on the chemical constituents of leaves of Camellia oleifera Abel. led to the isolation of 3 new bibenzyl glycosides. Their structures have been elucidated as 1-(3',5'-dihydroxy)phenyl-2-(4″-O-β-D-glucopyranosyl)phenylethane (1), 1-(3',5'-dimethoxy)phenyl-2-(4″-O-β-D-glucopyranosyl)phenylethane (2) and 1-(3',5'-dimethoxy)phenyl-2-[4″-O-β-D-glucopyranosyl(6→1)-O-α-L-rhamnopyranosyl]phenylethane (3) through spectral studies including HR-ESI-MS, ((1))H NMR, ((13))C NMR and 2D NMR experiments. All the above 3 bibenzyl glycosides showed cytotoxic activities to Hela and hep2 cell lines.
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http://dx.doi.org/10.1016/j.fitote.2010.12.009DOI Listing
April 2011

Two new secolignan glycosides from the roots of Urtica triangularis Hand.-Mazz.

Fitoterapia 2010 Sep 6;81(6):607-9. Epub 2010 Mar 6.

College of Bioengineering, Dalian University, Dalian 116622, China.

Two secolignan glycoside isomers, urticaside A (1) and urticaside B (2), were isolated from the roots of Urtica triangularis Hand.-Mazz. Their structures were elucidated by means of spectral analyses including 1D, 2D NMR and HR-EI-MS.
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http://dx.doi.org/10.1016/j.fitote.2010.03.002DOI Listing
September 2010

Model-based seizure detection method using statistically optimal filters.

Conf Proc IEEE Eng Med Biol Soc 2004;2006:45-8

Dept. of Electr. & Comput. Eng., Concordia Univ., Montreal, Que., Canada.

In this paper, a model-based seizure detection method using statistically optimal filters (SONFs) is presented. A template seizure from a patient is first selected and the basis functions required by the SONF are derived from this template seizure using wavelet transform. Subsequent EEG (electroencephalogram) recording is processed by the SONF and the output represents the noise-free estimate of the seizure. The energy ratio between the output and the input of the SONF is calculated and used as the test statistic for the seizure detection. Experiments using the SEEG (stereoelectroencephalogram, or intracerebral EEG) recordings of two patients show that this is an effective and promising method, with the possibility of reduced false detections.
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http://dx.doi.org/10.1109/IEMBS.2004.1403086DOI Listing
May 2007

A novel ZnII-sensitive fluorescent chemosensor assembled within aminopropyl-functionalized mesoporous SBA-15.

Inorg Chem 2006 Aug;45(17):6844-50

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.

A novel Zn2+-sensitive fluorescent chemosensor SC/SBA-15 has been obtained by the self-assembly of 4-chloroaniline-N-salicylidene (SC), a Schiff base ligand, within the channel of silylation-modified SBA-15 without destroying its hexagonally ordered mesoporous structure. The remarkable 200-fold fluorescence enhancement with a large Stokes shift of 180 nm in luminescence emission upon the addition of Zn2+ is attributed to the formation of a coordinate complex of a large rigid conjugate system and Zn2+ ions.
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http://dx.doi.org/10.1021/ic0516562DOI Listing
August 2006

Hypouricemic effects of acacetin and 4,5-o-dicaffeoylquinic acid methyl ester on serum uric acid levels in potassium oxonate-pretreated rats.

Biol Pharm Bull 2005 Dec;28(12):2231-4

Division of Natural Products Chemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-0194, Japan.

The effects of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2), compounds contained in the flowers of Chrysanthemum sinense SABINE, on the serum uric acid level were investigated using the rats pretreated with the uricase inhibitor potassium oxonate as an animal model for hyperuricemia. When administered per orally at doses of 20 and 50 mg/kg, 1 reduced the serum uric acid level by 49.9 and 63.9%, respectively and 2 reduced the level by 31.2 and 44.4%, respectively. On the other hand, when the same doses were given intraperitoneally, both of compounds also exhibited a dose-dependent and more marked reduction of the serum uric acid level (% reduction at 20 and 50 mg/kg were 63.0 and 95.1% in 1, respectively and 66.9 and 86.5% in 2, respectively). Furthermore, the compounds 1 and 2 inhibited the rat liver xanthine oxidase activity with IC(50) values of 2.22 muM and 5.27 muM, respectively. These results demonstrated the hypouricemic action of 1 and 2, which may be attributable to their xanthine oxidase inhibitory activity.
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http://dx.doi.org/10.1248/bpb.28.2231DOI Listing
December 2005