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parp 1

Qiu Yanling, Cheng Xiaoning, Bai Fei, Fang Liyun, Hu Huizhong, Sun Daqing
Acute lung injury (ALI), known a severe disease along with high morbidity and mortality, is lacking of specific therapies. Inflammation, apoptosis and oxidative stress are critical pathologies that contribute to ALI. Recently, there is study indicated that NLRP9b, a NOD-like receptor (NLR) member, is critical in modulation of inflammatory response. However, the effects of NLRP9b on sepsis-associated ALI, and the underlying molecular mechanism have not been understood. In the present study, the wild type (WT) and NLRP9b-knockout (NLRP9b-/- ) mice with C57B/L6 background were subjected to a cecal ligation and puncture (CLP) for ALI murine model establishment...
April 12, 2018: Biochemical and Biophysical Research Communications
Xiaomin Yi, Limin Xiang, Yuying Huang, Yihai Wang, Xiangjiu He
BACKGROUND: Our previous study has revealed that the spirostanol saponins isolated from the rhizomes of Rohdea chinensis (Baker) N. Tanaka (synonym Tupistra chinensis Baker) (Convallariaceae) (a reputed folk medicine) exhibited potent antiproliferative activity. However, the underlying mechanism of purified saponins remains unclear. More studies are necessary to assess the apoptosis and autophagy activities of the saponins from R. chinensis and clarify their antiproliferative mechanisms...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Siew-Li Lai, Mohd Rais Mustafa, Pooi-Fong Wong
BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Dong Zhen, Ling Su, Yue Miao, Fei Zhao, Guihong Ren, Shad Mahfuz, Hui Song
In this study, a homogeneous polysaccharide (designated as GAP-3S) with an average molecular weight of 6.82×105 Da was purified from Ganoderma applanatum. GAP-3S was composed of glucose, galactose, fucose and xylose in the molar ratio of 7.1:2.6:1.1:1. It could significantly inhibit the proliferation of MCF-7 cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that GAP-3S could also induce cell apoptosis. Treatment of MCF-7 cells with GAP-3S lead to the collapse of mitochondrial membrane potential and the accumulation of ROS, up-regulated expression of Bax, cleavage of PARP, p-p38 and p-JNK, and the down-regulated expression of Bcl-2, PARP and p-ERK...
April 10, 2018: International Journal of Biological Macromolecules
Mohamad El Amki, Dominique Lerouet, Marie Garraud, Fei Teng, Virginie Beray-Berthat, Bérard Coqueran, Benoît Barsacq, Charlotte Abbou, Bruno Palmier, Catherine Marchand-Leroux, Isabelle Margaill
Benefits from thrombolysis with recombinant tissue plasminogen activator (rt-PA) after ischemic stroke remain limited due to a narrow therapeutic window, low reperfusion rates, and increased risk of hemorrhagic transformations (HT). Experimental data showed that rt-PA enhances the post-ischemic activation of poly(ADP-ribose)polymerase (PARP) which in turn contributes to blood-brain barrier injury. The aim of the present study was to evaluate whether PJ34, a potent PARP inhibitor, improves poor reperfusion induced by delayed rt-PA administration, exerts vasculoprotective effects, and finally increases the therapeutic window of rt-PA...
April 12, 2018: Molecular Neurobiology
Hideki Shimodaira
Development of molecular targeted drugs has achieved remarkable improvement of systemic cancer therapy. Recently, the several molecular targeted drugs have become available which associated with the status of responsible genes for hereditary cancer syndrome. These drugs would allow to establish specific strategy for hereditary cancer syndrome or sporadic cancers with similar biological phenotype with hereditary cancer. Genetic tests for the diagnosis of hereditary cancer syndrome will have the meaning of biomarker for predicting the efficacy of these molecular targeted drugs...
April 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Gwynn Ison, Lynn J Howie, Laleh Amiri-Kordestani, Lijun Zhang, Shenghui Tang, Rajeshwari Sridhara, Vadryn Pierre, Rosane Charlab, Anuradha Ramamoorthy, Pengfei Song, Fang Li, Jingyu Yu, Wimolnut Manheng, Todd R Palmby, Soma Ghosh, Hisani N Horne, Eunice Y Lee, Reena Philip, Kaushalkumar Dave, Xiao Hong Chen, Sharon L Kelly, Kumar G Janoria, Anamitro Banerjee, Okponanabofa Eradiri, Jeannette Dinin, Kirsten B Goldberg, William F Pierce, Amna Ibrahim, Paul G Kluetz, Gideon M Blumenthal, Julia A Beaver, Richard Pazdur
The Food and Drug Administration approved niraparib, a poly ADP ribose polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint...
April 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Huiwen Ren, Xiangbo Meng, Jian Yin, Jingyan Sun, Qingfeng Huang, Zhuming Yin
BACKGROUND: Thioredoxin-1 (Trx-1) plays an important role in defensing the skin flap ischemia-reperfusion injury. Ganoderma lucidum polysaccharide peptide (GLPP) is the major component of Ganoderma lucidum, which possesses potent antioxidant and antiapoptotic activity. Our study aims to determine whether GLPP could attenuate the skin flap ischemia-reperfusion injury and investigate possible mechanisms involved. METHODS: The dermoprotective effect and mechanisms were assessed by an in vivo mouse ischemia-reperfusion flap model and an in vitro epithelial skin cell hypoxia/reoxygenation model...
March 29, 2018: Plastic and Reconstructive Surgery
Jie Zhou, Ming Ji, Haiping Yao, Ran Cao, Hailong Zhao, Xiaoyu Wang, Xiaoguang Chen, Bailing Xu
Novel quinazoline-2,4(1H,3H)-dione derivatives bearing a 3-amino pyrrolidine moiety were designed and synthesized as PARP-1/2 inhibitors. Structure-activity relationships were examined which revealed a number of potent PARP-1/2 inhibitors with moderate selectivity toward PARP-1 over PARP-2. These compounds had IC50 values against PARP-1 at the 10-9 M level and against PARP-2 at the 10-8 M level. Among all the synthesized compounds, compounds 10 and 11 displayed strong cytotoxicities which are either used as a single agent or in combination with temozolomide (TMZ) in MX-1 cells (10, IC50 < 3...
April 12, 2018: Organic & Biomolecular Chemistry
Sadia Afrin, Francesca Giampieri, Massimiliano Gasparrini, Tamara Y Forbes-Hernández, Danila Cianciosi, Patricia Reboredo-Rodriguez, Adolfo Amici, Josè L Quiles, Maurizio Battino
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentrations of MH (0-20 mg mL-1 for HCT-116 cells and 0-50 mg mL-1 for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression...
April 12, 2018: Food & Function
Eui-Baek Byun, Eun-Ji Cho, Yi-Eun Kim, Woo Sik Kim, Eui-Hong Byun
This study was carried out to evaluate the neuroprotective activity of polysaccharide extracts isolated from Perilla frutescens (PEPF) in H2 O2 -treated HT22 hippocampus cells. The PEPF treatment was found to increase the anti-oxidant activities of HT22 hippocampus cells. PEPF treatment resulted in a significant protection of HT22 hippocampus cells against H2 O2 -induced neurotoxicity, this protection ultimately occurred through an inhibition of ROS-mediated intracellular Ca2+ levels leading to MAPKs and NF-κB, as well as the accumulation of PI3K/AKT and Nrf2-mediated HO-1/NQO1 pathways...
April 8, 2018: Bioscience, Biotechnology, and Biochemistry
Ah Young Lee, Ji Myung Choi, Myoung Hee Lee, Jaemin Lee, Sanghyun Lee, Eun Ju Cho
BACKGROUND/OBJECTIVE: Oxidative stress plays a key role in neuronal cell damage, which is associated with neurodegenerative disease. The aim of present study was to investigate the neuroprotective effects of perilla oil (PO) and its active component, alpha-linolenic acid (ALA), against hydrogen peroxide (H2 O2 )-induced oxidative stress in SH-SY5Y neuronal cells. MATERIALS/METHODS: The SH-SY5Y human neuroblastoma cells exposed to 250 µM H2 O2 for 24 h were treated with different concentrations of PO (25, 125, 250 and 500 µg/mL) and its major fatty acid, ALA (1, 2...
April 2018: Nutrition Research and Practice
Halise Inci Gul, Cem Yamali, Merve Bulbuller, Petek Ballar Kirmizibayrak, Mustafa Gul, Andrea Angeli, Silvia Bua, Claudiu T Supuran
In this study, new dibenzensulfonamides, 7-9, having the chemical structure 4,4'-(5'-chloro-3'-methyl-5-aryl-3,4-dihydro-1'H,H-[3,4'-bipyrazole]-1',2-diyl)dibenzenesulfonamide were synthesized in five steps to develop new anticancer drug candidates. Their chemical structures were confirmed by1 H NMR,13 C NMR and HRMS spectra. Cytotoxicities of the dibenzensulfonamides were investigated towards HCC1937, MCF7, HeLa, A549 as tumor cell lines and towards MRC5 and Vero as non-tumor cells. Carbonic anhydrase (CAs, EC 4...
March 30, 2018: Bioorganic Chemistry
Yao Liu, Xiao Yan Ni, Rui Ling Chen, Juan Li, Feng Guang Gao
Tumor necrosis factor α‑induced protein 8 (TIPE) is highly expressed in many types of malignancies. Apoptosis is the process of programmed cell death which maintains the balance of cell survival and death. TIPE is involved in the carcinogenesis of many tumor types, yet the exact role of TIPE in defective apoptosis‑associated carcinogenesis remains uncertain. In the present study, TIPE‑overexpressing Raw264.7 and EL4 cells and vector control cells were treated with 4 mJ/cm2 ultraviolet radiation or 2 µg/ml cisplatin...
April 3, 2018: Oncology Reports
Christelle Colin, Maxime Meyer, Claudia Cerella, Alexandra Kleinclauss, Gérald Monard, Michel Boisbrun, Marc Diederich, Stéphane Flament, Isabelle Grillier-Vuissoz, Sandra Kuntz
15-Deoxy-∆12,14-prostaglandin J2 (15d‑PGJ2) is a natural agonist of peroxisome proliferator-activated receptor γ (PPARγ) that displays anticancer activity. Various studies have indicated that the effects of 15d‑PGJ2 are due to both PPARγ-dependent and -independent mechanisms. In the present study, we examined the effects of a biotinylated form of 15d‑PGJ2 (b‑15d‑PGJ2) on hormone-dependent MCF‑7 and triple‑negative MDA‑MB‑231 breast cancer cell lines. b‑15d‑PGJ2 inhibited cell proliferation more efficiently than 15d‑PGJ2 or the synthetic PPARγ agonist, efatutazone...
March 28, 2018: International Journal of Oncology
D K Nilov, K I Yashina, I V Gushchina, A L Zakharenko, M V Sukhanova, O I Lavrik, V K Švedas
We show for the first time that natural 2,5-diketopiperazines (cyclic dipeptides) can suppress the activity of the important anticancer target poly(ADP-ribose)polymerase (PARP). Cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) can interact with the key residues of the PARP-1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) forms hydrogen bonds with the Gly863 residue, while the second amide group can form a hydrogen bond with the catalytic residue Glu988, and the side chain can make a hydrophobic contact with Ala898...
February 2018: Biochemistry. Biokhimii︠a︡
Yu-Ru Zhao, Hong-Mei Li, Meilin Zhu, Jing Li, Tao Ma, Qiang Huo, Young-Soo Hong, Cheng-Zhu Wu
Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from the genetically engineered Streptomyces hygroscopicus , was found to haveanticancer activity against two human breast cancer cell lines.WK-88-1 produced concentration-dependent inhibition in cell proliferation, cell cycle arrest, and apoptosis inestrogen receptor (ER)-positive MCF-7 andER-negativeMDA-MB-231 cell lines...
April 6, 2018: Journal of Microbiology and Biotechnology
Chakrabhavi Dhananjaya Mohan, Nirvanappa C Anilkumar, Shobith Rangappa, Muthu K Shanmugam, Srishti Mishra, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Atanu Bhattacharjee, Gautam Sethi, Alan Prem Kumar, Basappa, Kanchugarakoppal S Rangappa
Aberrant activation of NF-κB is linked with the progression of human malignancies including hepatocellular carcinoma (HCC), and blockade of NF-κB signaling could be a potential target in the treatment of several cancers. Therefore, designing of novel small molecule inhibitors that target NF-κB activation is of prime importance in the treatment of several cancers. In the present work, we report the synthesis of series of 1,3,4-oxadiazoles, investigated their anticancer potential against HCC cells, and identified 2-(3-chlorobenzo[b]thiophen-2-yl)-5-(3-methoxyphenyl)-1,3,4-oxadiazole (CMO) as the lead compound...
2018: Frontiers in Oncology
Lin-Lin Yin, Xin-Mian Wen, Qing-Hua Lai, Jing Li, Xiu-Wen Wang
Lenalidomide is an immunomodulatory drug and possesses anti-angiogenic and immunomodulatory activities against multiple myeloma. The present study assessed the in vitro effect of lenalidomide combined with cisplatin on MDA-MB-231, a triple-negative breast cancer (TNBC) cell line and explored the underlying molecular mechanism of this combination. Cell viability, apoptosis and the protein expression of phosphorylated (p) and total extracellular signal-regulated kinase (ERK), B-cell lymphoma-2 (Bcl-2), caspase-3, cleaved poly-adenosine diphosphate-ribose polymerase (cPARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured in MDA-MB-231 cells treated with different concentrations of lenalidomide, cisplatin and their combination using different biochemical assays...
May 2018: Oncology Letters
Xiaoxiao Liu, Yunfei Deng, Yifeng Xu, Wei Jin, Hongli Li
Myocardial infarction (MI), characterized by interruption of blood and oxygen to myocardium, is a common yet fatal cardiovascular event that causes progressive damage to myocardial tissue and eventually leads to heart failure. Previous studies have shown increased expression of microRNA-223 (miR-223) in infarcted myocardial tissues of humans and in rat models of MI. However, the role of miR-223 in cell survival during MI has not been elucidated. Thus, we aimed to investigate whether miR-223 participates in the regulation of cardiac ischemia-induced injury and to elucidate the underlying mechanisms of this process...
March 30, 2018: Journal of Molecular and Cellular Cardiology
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