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https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#1
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340357/ruthenium-complexes-with-phenylterpyridine-derivatives-target-cell-membrane-and-trigger-death-receptors-mediated-apoptosis-in-cancer-cells
#2
Zhiqin Deng, Pan Gao, Lianling Yu, Bin Ma, Yuanyuan You, Leung Chan, Chaoming Mei, Tianfeng Chen
Elucidation of the communication between metal complexes and cell membrane may provide useful information for rational design of metal-based anticancer drugs. Herein we synthesized a novel class of ruthenium (Ru) complexes containing phtpy derivatives (phtpy = phenylterpyridine), analyzed their structure-activity relationship and revealed their action mechanisms. The result showed that, the increase in the planarity of hydrophobic Ru complexes significantly enhanced their lipophilicity and cellular uptake...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28340212/accelerated-senescence-in-skin-in-a-murine-model-of-radiation-induced-multi-organ-injury
#3
Elizabeth A McCart, Rajesh L Thangapazham, Eric D Lombardini, Steven R Mog, Ronald Allan M Panganiban, Kelley M Dickson, Rihab A Mansur, Vitaly Nagy, Sung-Yop Kim, Reed Selwyn, Michael R Landauer, Thomas N Darling, Regina M Day
Accidental high-dose radiation exposures can lead to multi-organ injuries, including radiation dermatitis. The types of cellular damage leading to radiation dermatitis are not completely understood. To identify the cellular mechanisms that underlie radiation-induced skin injury in vivo, we evaluated the time-course of cellular effects of radiation (14, 16 or 17 Gy X-rays; 0.5 Gy/min) in the skin of C57BL/6 mice. Irradiation of 14 Gy induced mild inflammation, observed histologically, but no visible hair loss or erythema...
March 18, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28339757/bone-characteristics-histopathology-and-chondrocyte-apoptosis-in-femoral-head-necrosis-induced-by-glucocorticoid-in-broilers
#4
M Zhang, C Y Shi, Z L Zhou, J F Hou
Femoral head necrosis (FHN) is a common disorder in fast-growing broilers in the poultry industry, but the pathogenesis of FHN has not been clarified completely. In the present study, glucocorticoid (GC) administration was used to induce FHN in broilers. Compared with normal birds, histopathology showed that the length of the articular cartilage of GC-induced FHN broilers was thicker while the proliferative zone and prehypertrophic zone were obviously thinner. Moreover, hematoxylin and eosin (HE) staining showed the apoptotic chondrocyte in the growth plate of the femoral head in FHN-affected birds...
February 22, 2017: Poultry Science
https://www.readbyqxmd.com/read/28337304/down-regulation-of-mediator-complex-subunit-19-med19-induces-apoptosis-in-human-laryngocarcinoma-hep2-cells-in-an-apaf-1-dependent-pathway
#5
Yan Zhao, Qingfeng Meng, Xu Gao, Lihua Zhang, Lixin An
Mediator 19 (Med19) is a component of the mediator complex which is a co-activator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The physiological mechanism by which Med19 exerts its promoting effects in laryngocarcinoma is not yet fully understood. Here, we found that the expression of Med19 was increased in laryngocarcinoma samples from patients compared to normal bone tissues...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337255/combined-therapy-with-melatonin-and-exendin-4-effectively-attenuated-the-deterioration-of-renal-function-in-rat-cardiorenal-syndrome
#6
Kuan-Hung Chen, Chih-Hung Chen, Christopher Glenn Wallace, Yen-Ta Chen, Chih-Chao Yang, Pei-Hsun Sung, Hsin-Ju Chiang, Yi-Ling Chen, Sarah Chua, Hon-Kan Yip, Jiin-Tsuey Cheng
This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337253/hepatoprotective-effects-of-antrodia-cinnamomea-the-modulation-of-oxidative-stress-signaling-in-a-mouse-model-of-alcohol-induced-acute-liver-injury
#7
Yange Liu, Juan Wang, Lanzhou Li, Wenji Hu, Yidi Qu, Yipei Ding, Lina Meng, Lirong Teng, Di Wang
In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28337252/small-interfering-rna-targeting-mitochondrial-calcium-uniporter-improves-cardiomyocyte-cell-viability-in-hypoxia-reoxygenation-injury-by-reducing-calcium-overload
#8
Yuriana Oropeza-Almazán, Eduardo Vázquez-Garza, Héctor Chapoy-Villanueva, Guillermo Torre-Amione, Gerardo García-Rivas
Intracellular Ca(2+) mishandling is an underlying mechanism in hypoxia/reoxygenation (H/R) injury that results in mitochondrial dysfunction and cardiomyocytes death. These events are mediated by mitochondrial Ca(2+) (mCa(2+)) overload that is facilitated by the mitochondrial calcium uniporter (MCU) channel. Along this line, we evaluated the effect of siRNA-targeting MCU in cardiomyocytes subjected to H/R injury. First, cardiomyocytes treated with siRNA demonstrated a reduction of MCU expression by 67%, which resulted in significant decrease in mitochondrial Ca(2+) transport...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28337145/dioscin-protects-anit-induced-intrahepatic-cholestasis-through-regulating-transporters-apoptosis-and-oxidative-stress
#9
Hong Yao, Youwei Xu, Lianhong Yin, Xufeng Tao, Lina Xu, Yan Qi, Xu Han, Pengyuan Sun, Kexin Liu, Jinyong Peng
Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28334043/cc-223-blocks-mtorc1-c2-activation-and-inhibits-human-hepatocellular-carcinoma-cells-in-vitro-and-in-vivo
#10
Zichen Xie, Jiqin Wang, Mei Liu, Deshan Chen, Chao Qiu, Keyu Sun
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28332739/gdf9-affects-the-development-and-tight-junction-functions-of-immature-bovine-sertoli-cells
#11
K Tang, L Wang, Y Jin, W Yang, L Yang
Transforming growth factor-β (TGFβ) superfamily are critical regulators of germ cell development that act as extracellular ligands of the signal transduction pathways regulating proliferation, apoptosis and other aspects of cell behaviour. As a member of the TGF-β superfamily, growth differentiation factor 9 (GDF9) plays a critical role in ovarian follicular development and the ovulation rate in females; however, its role in the testis has not been well elucidated. The aim of this study was to investigate the expression of GDF9 and its receptor genes BMPRII and ALK5 in prepuberal bovine Sertoli cells (SCs)...
March 23, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28331100/microrna-434-3p-regulates-age-related-apoptosis-through-eif5a1-in-the-skeletal-muscle
#12
Patricia S Pardo, Ameena Hajira, Aladin M Boriek, Junaith S Mohamed
Sarcopenia is caused by increased activation of catabolic pathways, including apoptosis. However, the mechanism underlying sarcopenia is not well understood. We report that aging alters miRNA expression profile as evidenced by miRNA microarray and real-time PCR. Our data show that miR-434-3p is highly downregulated miRNA in skeletal muscles of the aging mouse and provided the first evidence that miR-434 is a novel regulator of apoptosis. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and that inhibitory role of miR-434-3p was abolished by its antagomir, suggesting a role for miR-434-3p in apoptosis...
March 22, 2017: Aging
https://www.readbyqxmd.com/read/28331050/first-in-human-clinical-trial-of-oral-onc201-in-patients-with-refractory-solid-tumors
#13
Mark N Stein, Joseph R Bertino, Howard L Kaufman, Tina Mayer, Rebecca Moss, Ann Silk, Nancy Chan, Jyoti Malhotra, Lorna Rodriguez-Rodriguez, Joseph Aisner, Robert D Aiken, Bruce G Haffty, Robert S DiPaola, Tracie Saunders, Andrew Zloza, Sherri Damare, Yasmeen Beckett, Bangning Yu, Saltanat Najmi, Christian Gabel, Siobhan Dickerson, Ling Zheng, Wafik S El-Deiry, Joshua Allen, Martin Stogniew, Wolfgang Oster, Janice M Mehnert
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design...
March 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28330474/hypercholesterolemia-downregulates-autophagy-in-the-rat-heart
#14
Zoltán Giricz, Gábor Koncsos, Tomáš Rajtík, Zoltán V Varga, Tamás Baranyai, Csaba Csonka, Adrián Szobi, Adriana Adameová, Roberta A Gottlieb, Péter Ferdinandy
BACKGROUND: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart...
March 23, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28327651/inhibition-of-cathepsin-s-confers-sensitivity-to-methyl-protodioscin-in-oral-cancer-cells-via-activation-of-p38-mapk-jnk-signaling-pathways
#15
Ming-Ju Hsieh, Chiao-Wen Lin, Mu-Kuan Chen, Su-Yu Chien, Yu-Sheng Lo, Yi-Ching Chuang, Yi-Ting Hsi, Chia-Chieh Lin, Jui-Chieh Chen, Shun-Fa Yang
Oral cancer is one of the most common cancers in the world. Approximately 90% of oral cancers are subtyped to oral squamous cell carcinoma (OSCC). Despite advances in diagnostic techniques and improvement in treatment modalities, the prognosis remains poor. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. Methyl protodioscin (MP) is a furostanol bisglycoside with a wide range of beneficial effects, including anti-inflammatory and anti-cancer properties...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327595/x-linked-inhibitor-of-apoptosis-inhibits-apoptosis-and-preserves-the-blood-brain-barrier-after-experimental-subarachnoid-hemorrhage
#16
Cheng Gao, Hongwei Yu, Cong Yan, Wenyang Zhao, Yao Liu, Dongdong Zhang, Jingwei Li, Nan Liu
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327355/cytotoxic-and-apoptosis-inducing-activity-of-c21-steroids-from-the-roots-of-cynanchum-atratum
#17
Jian Zhang, Lin Ma, Zheng-Feng Wu, Shu-Le Yu, Lei Wang, Wen-Cai Ye, Qing-Wen Zhang, Zhi-Qi Yin
Two new(1-2) and two known C21steroids (3-4) were isolated from the roots of Cynanchum atratum. Their structures were elucidated by detailed 1D and 2D spectroscopic.The MTT assay showed that compounds 1-4 displayed obvious cytotoxic activities against HepG2 cells with IC50 values ranging from 10.19μM to 76.12μM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC50 values of 30.87-95.39 μM. Compound 3 showed the antiproliferative activity via G0/G1 cell cycle arrest and proapoptosis in HepG2 cells by Flowcytometry analysis...
March 18, 2017: Steroids
https://www.readbyqxmd.com/read/28326171/large-scale-isolation-and-cytotoxicity-of-extracellular-vesicles-derived-from-activated-human-natural-killer-cells
#18
Ambrose Y Jong, Chun-Hua Wu, Jingbo Li, Jianping Sun, Muller Fabbri, Alan S Wayne, Robert C Seeger
Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28325143/synthesis-and-characterization-of-a-new-benzo-indole-derivative-with-apoptotic-activity-against-colon-cancer-cells
#19
Fatemeh Hajiaghaalipou, Fadhil Lafta Faraj, Elham Bagheri, Hamid Khaledi, Hapipah Mohd Ali, Nazia Abdul Majid, Mahmood Ameen Abdulla
BACKGROUND: Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry. METHODS: A new synthetic compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-3-(2-hydroxy-phenylimino)-propionaldehyde, abbreviated as DBID has been synthesized by reaction of 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde with 2-aminophenol...
March 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28323210/the-protective-activity-of-mesothelial-cells-against-peritoneal-growth-of-gastrointestinal-tumors-the-role-of-soluble-icam-1
#20
Justyna Mikuła-Pietrasik, Paweł Uruski, Małgorzata Kucińska, Andrzej Tykarski, Krzysztof Książek
In this project we examined how the presence of human peritoneal mesothelial cells (HPMCs) modifies (supports or inhibits) colorectal and pancreatic cancer cell progression in mice peritoneal cavity. Experiments were performed using primary, omentum-derived HPMCs, commercially available colorectal (SW-480) and pancreatic (PSN-1) cancer cells, and immunocompromised SCID mice. Tumor growth within the peritoneal cavity was monitored using bioluminescence. Adhesion of the cancer cells to HPMCs was examined using a fluorescence-based method, while the incidence of apoptosis was quantified using flow cytometry...
March 17, 2017: International Journal of Biochemistry & Cell Biology
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