Genipin induces cyclooxygenase-2 expression via NADPH oxidase, MAPKs, AP-1, and NF-kB in RAW 264.7 cells

( Tilak Khanal ),( Hyung Gyun Kim ),( Minh Truong Do ),( Jae Ho Choi ),( Yong Chul Chung ),( Hee Suk Kim ),( Youn Joon Park ),( Tae Cheon Jeong ),( Hye Gwang Jeong ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Genipin is a compound found in gardenia fruit extract with diverse pharmacological activities. However, the mechanism underlying genipin-induced cyclooxygenase-2 (COX-2) expression remains unknown. In this study, we investigated the effects of genipin on COX-2 expression and determined that exposure to genipin dose-dependently enhanced the production of prostaglandin E2 (PGE2), a major COX-2 metabolite, in RAW 264.7 cells. These effects were mediated by genipin-induced activation of the COX-2 promoter, as well as AP-1 and NF-κB luciferase constructs. Phosphatidylinositol-3-kinase/Akt and MAPKs were also significantly activated by genipin, and Akt and MAPKs inhibitors (PD98059, SB20358, SP600125, and LY294002) inhibited genipin-induced COX-2 expression. Moreover, genipin increased production of the ROS and the ROS-producing NAPDH-oxidase (NOX) family oxidases, NOX2 and NOX3. Inhibition of NADPH with diphenyleneiodonium attenuated ROS production, COX-2 expression and NF-κB and AP-1 activation. These results suggest that the molecular mechanism mediating ROS-dependent COX-2 up-regulation and PGE2 production by genipin involves activation of Akt, MAPKs and AP-1/NF-κB.ⓒ2013 Elsevier Ltd. All rights reserved.

NONDIFFERENTIABLE SECOND-ORDER MINIMAX MIXED INTEGER SYMMETRIC DUALITY

Tilak Raj Gulati,Shiv Kumar Gupta 대한수학회 2011 대한수학회지 Vol.48 No.1

In this paper, a pair of Wolfe type nondifferentiable second order symmetric minimax mixed integer dual problems is formulated. Symmetric and self-duality theorems are established under η1/η2-boncavity assumptions. Several known results are obtained as special cases. Examples of such primal and dual problems are also given.

Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERα pathway

( Tilak Khanal ),( Hyung Gyun Kim ),( Minh Truong Do ),( Jae Ho Choi ),( Seong Su Won ),( Wonku Kang ),( Young Chul Chung ),( Tae Cheon Jeong ),( Hye Gwang Jeong ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells.ⓒ2014 Elsevier inc. All rights resenved.

Influence of MWCNT Fillers on the Elastic Properties of GFRP Hybrid Honeycomb Core: Numerical Study with Experimental Verification

Tilak Rana,Mesfin Kebede Kassa,Abhishek Shinde,Paul Praveen A,Sushila Chowdhary,Ananda Babu Arumugam 한국섬유공학회 2022 Fibers and polymers Vol.23 No.6

In this study, the elastic properties of the various honeycomb core configurations tailored with MWCNT filledglass fiber reinforced polymer composite materials (GFRP) were investigated numerically using vibration based techniquesand verified with experimental works. The shear properties of GFRP and CNT-GFRP strips corrugated hybrid honeycombcore structures with the influence of Armchair and Zigzag arrangement in CNTs using the vibration analysis have beencarried out along the out of plane with respect to Gxz and Gyz directions. The fabrication of honeycomb core using MWCNTfilled glass fiber reinforced polymer composite materials (GFRP) were prepared with corrugation method after preparing thelamina using vacuum bagging assisted hand layup technique and tested using vibration based techniques for verifying thedeveloped numerical formulation. Finally, the parametric study was carried out to identify the effects of the addition ofvarious different types of CNT; weight percentages of MWCNT, different ply orientations of the fibers, various honeycombconfigurations and honeycomb cell size. It was observed that significant difference is noticed in the shear characteristics ofthe honeycomb with respect to the variations in the parameters considered. Further, it was noticed from the analysis that thehoneycomb structures made by the insertion of strips in various locations of the hexagonal honeycomb cells could yieldhigher shear moduli than that of the conventional honeycomb structure. It can be concluded that the vibration basedtechniques implemented for evaluation the elastic properties of the various honeycomb core configurations tailored withMWCNT filled GFRP composite materials and results extracted could support the designers for developing various cell corewith the addition of MWCNT for the light weight applications such robots, aircraft and automobile applications.

Second-order symmetric duality in multiobjective programming over cones

Tilak Raj Gulati,Geeta Mehndiratta 대한수학회 2016 대한수학회지 Vol.53 No.1

In this paper, some omissions in Mishra and Lai \cite{mishralai'07}, have been pointed out and their corrective measures have been discussed briefly.

Protective role of metabolism by intestinal microflara in butyl paraben-induced toxicity in HepG2 cell cultures

( Tilak Khanal ),( Hyung Gyun Kim ),( Sun Woo Jin ),( Eol Shim ),( Hwa Jeong Han ),( Keumhan Noh ),( Sunkyoung Park ),( Dae Hun Lee ),( Wonku Kang ),( Hee Kyung Yeo ),( Dong Hyun Kim ),( Tae Cheon Jeo 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

Parabens are alkyl esters of p-hydroxybenzoic acid (BA), including methyl paraben (MP), ethyl paraben, propyl paraben (PP), and butyl paraben (BP). In the present study, possible role of metabolism by fecalase in BP-induced cytotoxicity was investigated in HepG2 cell cultures. As an intestinal bacterial metabolic system, a human fecalase prepared from human fecal specimen was employed. Among the parabens tested, cytotoxicity of BP was most severe. BA, the de-esterified metabolite, did not induce cytotoxicity when compared to other parabens. When BP was incubated with fecalase, it rapidly disappeared, in association with reduced cytotoxicity in HepG2 cells. In addition, BP incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved caspase-3. Moreover, anti-apoptotic effect by the incubation of BP with fecalase was also confirmed by the TUNEL assay. Furthermore, BP induced a sustained activation of the phosphorylation of JNK only when it was treated alone. Meanwhile, BP-induced cell death was reversed by the pre-incubation of BP with either fecalase or SP600125. Taken together, the findings suggested that metabolism of BP by human fecalase might have protective effects against BP-induced toxicity in HepG2 cells. ⓒ2012 Elsevier lreland Lrd. Al rights reserved.

Finite Element Modeling of Steel–Concrete–Steel Sandwich Beams with Bolt Connectors Under Drop Weight Impact

Tilak Prasad Sah,Yonghui Wang,Jingyi Lu 한국강구조학회 2021 International Journal of Steel Structures Vol.21 No.5

This paper develops a three-dimensional Finite Element (FE) model using the non-linear explicit code in LS-DYNA to predict the impact behavior of Steel–Concrete–Steel (SCS) sandwich beams with bolt connectors. The accuracy of the developed FE model is validated by comparing the FE-predicted impact force and displacement–time histories with the experimental results of the SCS sandwich beams. The FE prediction shows a close match with the test results. Using the validated FE model, parametric studies are carried out to investigate the infl uences of diff erent parameters, i.e., spacing of connectors, strength of concrete, presence of endplates, location of impact, mass of drop weight, and height of drop. It is found that the spacing of connectors and the strength of concrete have a limited infl uence on the impact resistance of the SCS sandwich beams with bolt connectors. However, the concrete strength signifi cantly aff ects the inertial peak impact force. The SCS sandwich beam without endplates shows higher deformation compared to the beam with endplates, and the location of impact exhibits infl uence on the impact resistance of the SCS sandwich beams. It is also revealed that the maximum displacements of the SCS sandwich beams could substantially rise with the increase in mass of drop weight and height of drop.

Life Science : Protective role of inestinal bacterial metabolism against baicalin-induced toxicity in HepG2 cell cultures

( Tilak Khanal ),( Hyung Gyun Kim ),( Jae Ho Choi ),( Bong Hwan Park ),( Minh Truong Do ),( Mi Jeong Kang ),( Hee Kyung Yeo ),( Dong Hyun Kim ),( Won Ku Kang ),( Tae Cheon Jeong ),( Hye Gwang Jeong ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

Baicalin, a glycoside present in Scutellaria baicalensis Georgi, is metabolized to its aglycone, baicalein, in intestine. In the present study, possible role of metabolism of baicalin by intestinalbacteria to baicalein in baicalin-induced toxicity was investigated in HepG2 cell cultures. As anintestinal bacterial metabolic system for baicalin, human fecal preparation containing intestinalmicroflora (fecalase) was employed. Initially, when cytotoxic effects of baicalin and baicalein were compared, baicalin was more cytotoxic than baicalein in HepG2 cells. When baicalin was incubated with fecalase, it was metabolized to baicalein. In addition, baicalin-incubated with fecalase reduced cytotoxicity of HepG2 cells in a concentration-dependent manner. Moreover, baicalin-incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved Caspase-3. Furthermore, anti-apoptotic effect by the incubation of baicalin with fecalase was also confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken all together, the findings suggested that metabolism of baicalin by human fecalase to baicalein might have protective effects against baicalin-induced toxicity in HepG2cells.

Experimental and analytical behaviour of cogged bars within concrete filled circular tubes

Tilak Pokharel,Huang Yao,Helen M. Goldsworthy,Emad F. Gad 국제구조공학회 2016 Steel and Composite Structures, An International J Vol.20 No.5

Recent research on steel moment-resisting connection between steel beams and concrete filled steel tubes has shown that there are considerable advantages to be obtained by anchoring the connection to the concrete infill within the tube using anchors in blind bolts. In the research reported here, extensive experimental tests and numerical analyses have been performed to study the anchorage behaviour of cogged deformed reinforcing bars within concrete filled circular steel tubes. This data in essential knowledge for the design of the steel connections that use anchored blind bolts, both for strength and stiffness. A series of pull-out tests were conducted using steel tubes with different diameter to thickness ratios under monotonic and cyclic loading. Both hoop strains and longitudinal strains in the tubes were measured together with applied load and slip. Various lead-in lengths before the bend and length of tailed extension after the bend were examined. These dimensions were limited by the dimensions of the steel tube and did not meet the requirements for “standard” cogs as specified in concrete standards such as AS 3600 and ACI 318. Nevertheless, all of the tested specimens failed by bar fracture outside the steel tubes. A comprehensive 3D Finite Element model was developed to simulate the pull-out tests. The FE model took into account material nonlinearities, deformations in reinforcing bars and interactions between different surfaces. The FE results were found to be in good agreement with experimental results. This model was then used to conduct parametric studies to investigate the influence of the confinement provided by the steel tube on the infilled concrete.

NONDIFFERENTIABLE SECOND-ORDER MINIMAX MIXED INTEGER SYMMETRIC DUALITY

Gulati, Tilak Raj,Gupta, Shiv Kumar Korean Mathematical Society 2011 대한수학회지 Vol.48 No.1

In this paper, a pair of Wolfe type nondifferentiable sec-ond order symmetric minimax mixed integer dual problems is formu-lated. Symmetric and self-duality theorems are established under $\eta_1$-bonvexity/$\eta_2$-boncavity assumptions. Several known results are obtained as special cases. Examples of such primal and dual problems are also given.