385 research outputs found
QSAR studies on Withanolide analogs for anticancer activity
No full textWithanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian systems of medicine. Withanolides are basically steroidal lactones (highly oxygenated C-28 phytochemicals) and similar to ginsenosides activity. Some of the withanolides that have been reported possess immunomodulatory, and anticancer activities. In the present investigation, a quantitative structure activity relationship (QSAR) model based on forward stepwise multiple linear regression (MLR) has been developed against the MCF7, MCF7/BUS, and SK-Br-3 human solid tumor breast cancer cell lines. Relationship correlation coefficient (r2) and cross validation correlation coefficient (r2CV) of QSAR model were 0.77 and 0.73 for MCF7, 0.91 and 0.85 for MCF7/BUS, 0.93 and 0.90 for SK-Br-3 respectively. Developed QSAR model was also evaluated for prediction accuracy through internal, external and randomization validation methods. The QSAR study indicates that chemical descriptors viz., atom count (all atoms), connectivity index (order 2, standard), for MCF7, Connectivity Index (order 0, standard), Dipole Vector X (debye), Molar Refractivity, Shape Index (basic kappa, order 2) for SK-Br-3 and Atom Count (all atoms), Dielectric Energy (kcal/mole), Total Energy (Hartree), Heat of Formation (kcal/mole) for MCF7/BUS are correlate well with the breast cancer activity, Moreover, on the basis of screening for oral bioavailability, in silico ADME and toxicity risk assessment, we concluded that compounds W3, W4, W8 have markedly higher anticancer activity compared to control. These results can offer useful references for directing the molecular design of lead compound(s) based on withanolide or analogous template with improved activity
Extended bounce-kinetic model for trapped electron mode turbulence
No full text© 2022 Author(s).The bounce-kinetic model based on the modern nonlinear bounce-kinetic theory [Fong and Hahm, Phys. Plasmas 6, 188 (1999)] has been developed and used for simulations previously. This work reports on an extension of the bounce-kinetic model including more accurate treatment of barely trapped particles and its implementation in the Gyro-Kinetic Plasma Simulation Program gyrokinetic code [Kwon et al., Comp. Phys. Commun. 215, 81 (2017)]. This leads to more accurate gyrokinetic simulations of the collisionless trapped electron mode at low magnetic shear.N
sj-docx-1-hpq-10.1177_13591053231224177 – Supplemental material for Is fear of disease progression associated with antiretroviral therapy adherence in persons with HIV/AIDS?
No full textSupplemental material, sj-docx-1-hpq-10.1177_13591053231224177 for Is fear of disease progression associated with antiretroviral therapy adherence in persons with HIV/AIDS? by Chan-Woo Yeom, Hyeju Ha, Bong-Jin Hahm, Sun Hee Lee, Nam Joong Kim and Eun-Jung Shim in Journal of Health Psychology</p
GIT1유전자 결손 형질전환 마우스 및 이를 이용한 약물 스크리닝 방법
No full textProvided is a method of using any mammal except humans, in particular, a mammal as an attention deficit hyperactivity disorder model, wherein genes of G protein-coupled receptor kinase interacting protein 1 (GIT1) as a neuronal synapse protein in the brain are knocked out from the mammal. In addition, disclosed is analysis of GIT1 knock-out mice in aspects of molecular biology, cellular biology, electrical biology and animal behavior and, more particularly, a screening method of novel drug, wherein excessive behavior as an attention deficit hyperactive disorder as well as recovery of theta wave in the frontal lobe are observed by administering a candidate material of the drug, thereby inducing recovery of the attention deficit hyperactivity disorder
시냅스 단백질 GIT1의 neuronal function에 관한 연구
No full text학위논문(석사) - 한국과학기술원 : 생명과학과, 2008.2, [ iv, 46 p. ]GIT1 is a synaptic scaffolding protein that interacts with various pre- and postsynaptic proteins, and is expressed in various brain regions. To investigate in vivo functions of GIT1, we have generated GIT1 knockout mice using genetrap. Immunoblot analysis revealed that expression levels of βPix, a binding partner of GIT1, were reduced in GIT1 mutant mice. Electrophysiological data showed that the basal synaptic transmission was increased and LTP was reduced in GIT1-/- mice. In behavioral analyses, GIT1-/- mice showed enhanced locomotor activity and lowered anxiety. In addition, GIT1-/- mice showed impaired motor coordination and motor learn. Lastly, spatial learning was impaired in GIT1-/- mice. These results indicate GIT1 is an important regulator of synaptic plasticity, anxiety, and spatial and motor learning.한국과학기술원 : 생명과학과
Abstract 5270: Disease subtype independent biomarkers of breast cancer prevention by withaferin a
No full textAbstract
Breast cancer is a rather complex and heterogeneous disease broadly grouped into four major subtypes, including luminal-type, basal-like, HER2 amplified, and normal-like, and each with a distinct molecular signature. A non-toxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study not only demonstrates chemoprevention of breast cancer in rats by the Ayurvedic medicine phytochemical withaferin A (WA) but also identifies its mechanistic biomarkers common to different subtypes of this disease. Chemopreventive efficacy of WA (4 and 8 mg per kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU). The mechanisms underlying breast cancer chemoprevention by WA were elucidated by western blotting, biochemical assays, immunohistochemistry, and cytokine profiling using plasma and tumors from the MNU-rat and/or mouse mammary tumor virus-neu (MMTV-neu) models. Inhibitory effect of WA on exit from mitosis and leptin-induced oncogenic signaling was determined using MCF-7 and MDA-MB-231 cells. Incidence, multiplicity, and burden of MNU-induced breast cancer in rats were decreased by WA administration. For example, the tumor weight in the 8 mg per kg group was lower by 67% compared with controls (P = 0.004). Mitotic arrest and apoptosis induction were common determinants of breast cancer chemoprevention by WA in the MNU-rat and MMTV-neu models. Cytokine profiling showed suppression of plasma leptin levels by WA in rats. WA inhibited leptin-induced oncogenic signaling in cultured MCF-7 and MDA-MB-231 cell lines. WA is a promising phytochemical with the ability to inhibit at least two different subtypes of breast cancer, including neu-driven estrogen receptor negative (ER-) breast cancer in MMTV-neu model and MNU-induced ER+ breast cancer in rats. This study was supported by the grant RO1 CA142604-07 awarded by the National Cancer Institute.
Citation Format: Eun-Ryeong Hahm, Suman K. Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Subrata K. Pore, Krishna B. Singh, Susan M. Christner, Yongli Shuai, Jan H. Beumer, Ruchi Roy, Nancy E. Davidson, Shivendra V. Singh. Disease subtype independent biomarkers of breast cancer prevention by withaferin a [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2017-5270</jats:p
Abstract 566: Withaferin A causes autophagy in normal as well as cancerous human breast cells
No full textAbstract 3787: D, L-Sulforaphane inhibits constitutive and interleukin 6-induced activation of signal transducer and activator of transcription 3 in human prostate cancer cells
No full textAbstract
D, L-Sulforaphane (SFN), a synthetic analogue of broccoli-derived L-isomer, inhibits viability of human prostate cancer cells in culture and in vivo. We also showed recently that oral administration of SFN prevents development of prostate cancer and pulmonary metastasis in a transgenic mouse model (TRAMP mice) by reducing cell proliferation and augmenting activity of natural killer cells. However, the mechanism underlying anticancer effect of SFN is not fully understood. We now demonstrate that SFN inhibits constitutive and interleukin 6 (IL6)-induced activation of signal transducer and activator of transcription 3 (STAT3), which is implicated in development and progression of prostate cancer. Growth suppressive concentrations of SFN (20 and 40 μmol/L) inhibited constitutive (DU145 cells) and IL6-induced (LNCaP cells) phosphorylation of STAT3 (Tyr705) as well as its upstream regulator Janus-activated kinase 2 (JAK2; Tyr1007/1008). Treatment of DU145 and LNCaP cells with SFN resulted in suppression of IL6-induced transcriptional activity of STAT3 as revealed by luciferase reporter assay and nuclear translocation of STAT3 as judged by immunofluorescence microscopy. The SFN-mediated inhibition of STAT3 activation was due to down-regulation of JAK2 mRNA expression in both cell lines. Levels of many STAT3-regulated gene products including Bcl-2, cyclin D1, and survivin were also down-regulated in SFN-treated cells. The IL6-mediated activation of STAT3 conferred partial but marked protection against SFN-induced apoptosis in LNCaP cells as evidenced by cleavage of poly-(ADP-ribose)-polymerase and caspase-3 and cytoplasmic histone-associated DNA fragmentation. In addition, siRNA knockdown of STAT3 in DU145 cells resulted in a modest yet statistically significant increase in SFN-induced apoptotic DNA fragmentation. The results of the present study demonstrate SFN-mediated inhibition of STAT3 activation in human prostate cancer cells. This investigation was supported by the National Cancer Institute grant CA115498-05.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3787.</jats:p
Cytoprotective autophagy induction by withaferin A in prostate cancer cells involves GABARAPL1
No full text
- …
