Synthesis and Biological Evaluation of Heterocyclic Ring-substituted Chalcone Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

Zhen-Hua Chen,Liang-Peng Sun,Wei Zhang,Qiang Shen,Li-Xin Gao,Jia Li,Hu-Ri Piao 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.5

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound (4) was first observed to have moderate inhibitory activity against PTP1B with an IC50 value of 13.72 ± 1.53 μM. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound (4) as the lead compound. Compound 4l (IC50 = 3.12 ± 0.18 μM) was 4.4-fold more potent than the lead compound 4 (IC50 = 13.72 ± 1.53 μM), and more potent than the positive control, ursolic acid (IC50 = 3.40 ± 0.21 μM). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells

Zhen-Xian Du,Hai-Yan Zhang,Da-Xin Gao,Hua-Qin Wang,Yong-Jun Li,Guo-Liang Liu 생화학분자생물학회 2006 Experimental and molecular medicine Vol.38 No.3

apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (MTC) and a MTC cell line TT, correlate suvivin expression with clinicopathologic features of MTC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffinembedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin- targeted gene therapy for MTC.

Post-fire Bond Behaviors Between Grout and Steel Rebar

Liang-Lin Liu,Chun-Yong Luo,Lu-Xia Ouyang,Zhen-Hua Xia,Wei-Hua Li 한국콘크리트학회 2022 International Journal of Concrete Structures and M Vol.16 No.5

Firstly, according to the theoretical analysis, the force mechanism and failure modes were assured for the bond behavior between grout and steel rebar. Then, a pull-out experiment was exerted to probe the bond behavior developments of specimens after exposed to 500 °C. It is found that the mixed measures of pre-drying and slow elevating rate, i.e., 5 °C/min, inhibits the explosive spalling in grout with compressive strength of 76.7 MPa. In addition, there are two failure modes including the steel rebar fracture and the bond slip failure in the test. Based on the elevated temperature, compressive strength of post-fire grout, diameter of steel rebar and its embedment length, a new expression has been built to calculate the bond strength between grout and steel rebar of post-fire specimens. Furthermore, the finite element simulation is employed to investigate the bond behaviors of pull-out specimens after exposed to elevated temperatures up to 500 °C. The steel rebar fracture is captured firstly in the pull-out test simulation. Moreover, it is found that the peak slips increase and peak loads decrease along with the temperature elevating. Finally, it is proposed that the crucial elevated temperatures of the failure mode change should be 300, 300 and 400 °C for the specimens with embedment lengths of 6, 7 and 8 times diameter of steel rebar with diameter of 16 mm, respectively, which is beneficial for evaluating the fire safety of the existing structure elements.

Synthesis and Biological Evaluation of Heterocyclic Ring-substituted Chalcone Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B

Chen, Zhen-Hua,Sun, Liang-Peng,Zhang, Wei,Shen, Qiang,Gao, Li-Xin,Li, Jia,Piao, Hu-Ri Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.5

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound ($\mathbf{4}$) was first observed to have moderate inhibitory activity against PTP1B with an $IC_{50}$ value of $13.72{\pm}1.53{\mu}M$. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound ($\mathbf{4}$) as the lead compound. Compound $\mathbf{4l}$ ($IC_{50}=3.12{\pm}0.18{\mu}M$) was 4.4-fold more potent than the lead compound $\mathbf{4}$ ($IC_{50}=13.72{\pm}1.53{\mu}M$), and more potent than the positive control, ursolic acid ($IC_{50}=3.40{\pm}0.21{\mu}M$). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

Effect of polymer and additive on the structure and property of porous stainless steel hollow fiber

Xiao-Hua Ma,Zhen-Liang Xu,Yu Bai,Yue Cao 한국화학공학회 2014 Korean Journal of Chemical Engineering Vol.31 No.8

Porous stainless steel hollow fiber has been widely used due to its high mechanical strength, excellentthermal conductivity and good sealing properties compared with other porous supports. We successfully prepared porousstainless steel hollow fibers using polyacrylonitrile (PAN) as polymer via dry-wet spinning followed by sintering throughtemperature programming method. The PAN concentration had an obvious impact on the structure and property ofporous stainless steel hollow fiber even if it would be burned off during sintering. The results showed that the morphologycould be tuned by adjusting the concentration of PAN. With increasing PAN concentration in casting solutionfor spinning, the viscosity was increased dramatically, resulting in much compact structures with high pure water flux(higher than 3×105 L·m−2·h−1·Pa−1). A more dense structure could be obtained by adding additive polyvinylpyrrolidone(PVP) as viscosity enhancer.

Highly heat-resistant NF membrane modified by quinoxaline diamines for Li+ extraction from the brine

Huan-Yin Xie,Run-Hua Tang,Gui-E Chen,Zhen-Liang Xu,Haifang Mao 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.112 No.-

The Functional layers with excellent heat-resistence nanofiltration (HRN) property were designed by fixingthermal stabilized quinoxaline diamines (QHDA) on poly (m-phenyleneisophthalamide) (PMIA) substratethrough interfacial polymerization. QHDA was used as aqueous monomer while cinnamoylchloride (CNC), isophthaloyl chloride (IPC) and trimesoyl chloride (TMC) were served as organic monomersto realize the immobilization of thermally stable N heterocycles. The experimental results statedclearly that the compact package reaction of QHDA with TMC lead a raise of thermal stability and saltsrejection at high temperature stream. With the optimal TMC and 0.5 wt.% QHDA, the as-developed membraneachieved the excellent NF performance and thermal stability. The rejection of MgSO4 reached to94.6 % at 30 C and hardly decrease at 90 C. The reduction in rejection was satisfactory at high temperatures. The functional layer still showed highly stability after 10 h long-term operation at 90 C with only2.8 % reduction in MgSO4 rejection. Besides, the excellent Mg2+ and poor Li+ rejection made this membranehave huge potential in the application of extracting Li+ from brine. The separation factor ofMg2+-Li+ at high temperature was satisfactory. Over all, this study offered a prospect technology toexploit heat-resistant membranes for extraction lithium at high temperature.

Subcellular Characterization of Porcine Oocytes with Different Glucose-6-phosphate Dehydrogenase Activities

Fu, Bo,Ren, Liang,Liu, Di,Ma, Jian-Zhang,An, Tie-Zhu,Yang, Xiu-Qin,Ma, Hong,Zhang, Dong-Jie,Guo, Zhen-Hua,Guo, Yun-Yun,Zhu, Meng,Bai, Jing Asian Australasian Association of Animal Productio 2015 Animal Bioscience Vol.28 No.12

The in vitro maturation (IVM) efficiency of porcine embryos is still low because of poor oocyte quality. Although brilliant cresyl blue positive (BCB+) oocytes with low glucose-6-phosphate dehydrogenase (G6PDH) activity have shown superior quality than BCB negative (-) oocytes with high G6PDH activity, the use of a BCB staining test before IVM is still controversial. This study aimed to shed more light on the subcellular characteristics of porcine oocytes after selection using BCB staining. We assessed germinal vesicle chromatin configuration, cortical granule (CG) migration, mitochondrial distribution, the levels of acetylated lysine 9 of histone H3 (AcH3K9) and nuclear apoptosis features to investigate the correlation between G6PDH activity and these developmentally related features. A pattern of chromatin surrounding the nucleoli was seen in 53.0% of BCB+ oocytes and 77.6% of BCB+ oocytes showed peripherally distributed CGs. After IVM, 48.7% of BCB+ oocytes had a diffused mitochondrial distribution pattern. However, there were no significant differences in the levels of AcH3K9 in the nuclei of blastocysts derived from BCB+ and BCB- oocytes; at the same time, we observed a similar incidence of apoptosis in the BCB+ and control groups. Although this study indicated that G6PDH activity in porcine oocytes was correlated with several subcellular characteristics such as germinal vesicle chromatin configuration, CG migration and mitochondrial distribution, other features such as AcH3K9 level and nuclear apoptotic features were not associated with G6PDH activity and did not validate the BCB staining test. In using this test for selecting porcine oocytes, subcellular characteristics such as the AcH3K9 level and apoptotic nuclear features should also be considered. Adding histone deacetylase inhibitors or apoptosis inhibitors into the culture medium used might improve the efficiency of IVM of BCB+ oocytes.

Plasma metabolites associated with physiological and biochemical indexes indicate the effect of caging stress on mallard ducks (Anas platyrhynchos)

Zheng Chao,Wu Yan,Liang Zhen Hua,Pi Jin Song,Cheng Shi Bin,Wei Wen Zhuo,Liu Jing Bo,Lu Li Zhi,Zhang Hao 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.2

Objective: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks. Methods: Liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database. Results: The results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. Conclusion: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted. Objective: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks.Methods: Liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database.Results: The results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism.Conclusion: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted.

Characteristics and Comparisons of Morphometric Measurements and Computed Tomography Hounsfield Unit Values of C2 Laminae for Translaminar Screw Placement Between Patients With and Without Basilar Invagination

Lu-Ping Zhou,Jin Shang,Zhi-Gang Zhang,Zhen-Fei Jiang,Hua-Qing Zhang,Chong-Yu Jia,Ren-Jie Zhang,Cai-Liang Shen 대한척추신경외과학회 2022 Neurospine Vol.19 No.4

Objective: Patients with basilar invagination (BI) had high incidences of vertebral variations and high-riding vertebral artery (HRVA) that might restrict the use of pedicle or pars screw and increase the use of translaminar screw on axis. Here, we conducted a radiographic study to investigate the feasibility of translaminar screws and the bone quality of C2 laminae in patients with BI, which were compared with those without BI as control to provide guidelines for safe placement. Methods: In this study, a total of 410 patients (205 consecutive patients with BI and 205 matched patients without BI) and 820 unilateral laminae of the axis were included at a 1:1 ratio. Comparisons with regard to insertion parameters (laminar length, thickness, angle, and height) for C2 translaminar screw placement and Hounsfield unit (HU) values for the assessment of the appropriate bone mineral density of C2 laminae between BI and control groups were performed. Besides, the subgroup analyses based on the Goel A and B classification of BI, HRVA, atlas occipitalization, and C2/3 assimilation were also carried out. Furthermore, the factors that might affect the insertion parameters and HU values were explored through multiple linear regression analyses. Results: The BI group showed a significantly smaller laminar length, thickness, height, and HU value than the control group, whereas no significant difference was observed regarding the laminar angle. By contrast, the control group showed significantly higher rates of acceptability for unilateral and bilateral translaminar screw fixations than the BI group. Subgroup analyses showed that the classification of Goel A and B, HRVA, atlas occipitalization, and C2/3 assimilation affected the insertion parameters except the HU values. Multiple linear regression indicated that the laminar length was significantly associated with the male gender (B = 0.190, p < 0.001), diagnoses of HRVA (B = -0.109, p < 0.001), Goel A (B = -0.167, p < 0.001), and C2/3 assimilation (B = -0.079, p = 0.029); the laminar thickness was significantly associated with the male gender (B = 0.353, p < 0.001), diagnoses of HRVA (B = -0.430, p < 0.001), Goel B (B = -0.249, p = 0.026), and distance from the top of odontoid to the Chamberlain line (B = -0.025, p = 0.003); laminar HU values were significantly associated with age (B = -2.517, p < 0.001), Goel A (B = -44.205, p < 0.001), Goel B (B = -25.704, p = 0.014), and laminar thickness (B = -11.706, p = 0.001). Conclusion: Patients with BI had narrower and smaller laminae with lower HU values and lower unilateral and bilateral acceptability for translaminar screws than patients without BI. Preoperative 3-dimensional computed tomography (CT) and CT angiography were needed for BI patients.