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https://www.readbyqxmd.com/read/28431339/novel-coumarin-and-quinolinone-based-polycycles-as-cell-division-cycle-25-a-and-c-phosphatases-inhibitors-induce-proliferation-arrest-and-apoptosis-in-cancer-cells
#1
Clemens Zwergel, Brigitte Czepukojc, Emilie Evain-Bana, Zhanjie Xu, Giulia Stazi, Mattia Mori, Alexandros Patsilinakos, Antonello Mai, Bruno Botta, Rino Ragno, Denise Bagrel, Gilbert Kirsch, Peter Meiser, Claus Jacob, Mathias Montenarh, Sergio Valente
Cell division cycle phosphatases CDC25 A, B and C are involved in modulating cell cycle processes and are found overexpressed in a large panel of cancer typology. Here, we describe the development of two novel quinone-polycycle series of CDC25A and C inhibitors on the one hand 1a-k, coumarin-based, and on the other 2a-g, quinolinone-based, which inhibit either enzymes up to a sub-micro molar level and at single-digit micro molar concentrations, respectively. When tested in six different cancer cell lines, compound 2c displayed the highest efficacy to arrest cell viability, showing in almost all cell lines sub-micro molar IC50 values, a profile even better than the reference compound NCS95397...
April 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431037/gestational-diabetes-alters-functions-in-offspring-s-umbilical-cord-cells-with-implications-for-cardiovascular-health
#2
Ajith Isaac Amrithraj, Anjaneyulu Kodali, Linh Nguyen, Adrian Kee Keong Teo, Cheng Wei Chang, Neerja Karnani, Kai Lyn Ng, Peter D Gluckman, Yap Seng Chong, Walter Stünkel
As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. We have assessed primary umbilical cord derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and non-GDM mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430938/characterization-of-yjjj-toxin-of-escherichia-coli
#3
Yuki Maeda, Chun-Yi Lin, Yojiro Ishida, Masayori Inouye, Yoshihiro Yamaguchi, Sangita Phadtare
Reminiscent of eukaryotic apoptotic programmed cell death, bacteria also contain a large number of suicide genes, which are in general co-expressed with their cognate antitoxic genes. These systems called the toxin-antitoxin (TA) systems are associated with cellular dormancy, and play major roles in biofilm formation and persistent multi-drug resistance of many human pathogens. In recent years, the study on TA system toxins has become a hot topic due to the health implications of these toxins by virtue of their role in bacterial pathogenicity...
April 19, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28430874/developmental-sall2-transcription-factor-a-new-player-in-cancer
#4
Viviana E Hermosilla, Matias I Hepp, David Escobar, Carlos Farlas, Elizabeth N Riffo, Ariel F Castro, Roxana Pincheira
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers, and is a specific biomarker for Synovial Sarcoma...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430795/igm-antibodies-to-oxidized-phosphatidylserine-as-protection-markers-in-cardiovascular-disease-among-60-year-olds
#5
Johan Frostegård, Jun Su, Sudhir Sing, Xiang Hua, Max Vikström, Karin Leander, Bruna Gigante, Ulf de Faire, Anna G Frostegård
OBJECTIVE: Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS: Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected...
2017: PloS One
https://www.readbyqxmd.com/read/28430789/mir-9-3p-augments-apoptosis-induced-by-h2o2-through-down-regulation-of-herpud1-in-glioma
#6
Ling Yang, Yongping Mu, Hongwei Cui, Yabing Liang, Xiulan Su
MicroRNAs are short, single-stranded non-coding RNA molecules that function as regulators of tumor progression in various cancers, including glioma. The present study sought to investigate the biological functions of miR-9-3p in glioma progression. The results of a microRNA microarray indicated that microRNA-9-3p (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas compared with non-tumor tissues. These results were confirmed with real-time PCR. The miR-9-3p expression level was associated with age and tumor grade...
2017: PloS One
https://www.readbyqxmd.com/read/28430645/midkine-promotes-hepatocellular-carcinoma-metastasis-by-elevating-anoikis-resistance-of-circulating-tumor-cells
#7
Bin Sun, Congli Hu, Zhibin Yang, Xiaofeng Zhang, Linlin Zhao, Junye Xiong, Junyong Ma, Lei Chen, Haihua Qian, Xiangji Luo, Lehua Shi, Jun Li, Xianshuo Cheng, Zhengfeng Yin
Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in tumor progression, but less is known about its role in resistance of circulating tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim of the present study was to analyze whether midkine was associated with HCC progression with anoikis resistance. We found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430358/regulation-of-axon-arborization-pattern-in-the-developing-chick-ciliary-ganglion-possible-involvement-of-caspase-3
#8
Hidetaka Katow, Teppei Kanaya, Tomohisa Ogawa, Ryo Egawa, Hiromu Yawo
During a certain critical period in the development of the central and peripheral nervous systems, axonal branches and synapses are massively reorganized to form mature connections. In this process, neurons search their appropriate targets, expanding and/or retracting their axons. Recent work suggested that the caspase superfamily regulates the axon morphology. Here, we tested the hypothesis that caspase 3, which is one of the major executioners in apoptotic cell death, is involved in regulating the axon arborization...
April 21, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28430184/the-ubiquitin-ligase-lin41-trim71-targets-p53-to-antagonize-cell-death-and-differentiation-pathways-during-stem-cell-differentiation
#9
Duong Thi Thuy Nguyen, Daniel Richter, Geert Michel, Sibylle Mitschka, Waldemar Kolanus, Elisa Cuevas, F Gregory Wulczyn
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#10
Xingyue Xu, Junnan Hu, Zhi Liu, Rui Zhang, Yufang He, Wei Hou, Zhiqing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is the most frequent inducement of drug-induced acute liver injury (ALI). The purpose of this study was to investigate the protective effect of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity and the involved mechanism were investigated. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for seven days before being treated with 250 mg/kg APAP. Sever liver injury was exerted at 24 h post-APAP and hepatotoxicity was assessed...
April 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28429453/tolcapone-induces-oxidative-stress-leading-to-apoptosis-and-inhibition-of-tumor-growth-in-neuroblastoma
#11
Tyler Maser, Maria Rich, David Hayes, Ping Zhao, Abhinav B Nagulapally, Jeffrey Bond, Giselle Saulnier Sholler
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis...
April 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28429052/the-skeletal-impact-of-the-chemotherapeutic-agent-etoposide
#12
A J Koh, B P Sinder, P Entezami, L Nilsson, L K McCauley
Effects of the chemotherapeutic agent etoposide on the skeleton were determined in mice. Numbers of bone marrow cells were reduced and myeloid cells were increased. Bone volume was significantly decreased with signs of inhibition of bone formation. Etoposide after pre-treatment with zoledronic acid still reduced bone but overall bone volume was higher than with etoposide alone. INTRODUCTION: Chemotherapeutics target rapidly dividing tumor cells yet also impact hematopoietic and immune cells in an off target manner...
April 20, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28428827/fundamental-research-on-the-action-mechanism-of-the-800-nm-semiconductor-laser-on-skin-blackheads-and-coarse-pores
#13
Jie Lin, Li Jing, Hao Zhu, Fu-Sheng Dong
The aim of the study was to determine the mechanism of action of the 800 nm semiconductor laser on skin blackheads and coarse pores. A total of 24 healthy purebred short-haired male guinea pigs, weighing 350-400 g, were selected and smeared with 0.5 ml coal tar suspension evenly by injector once daily. Treatment was continued for 14 days to form an experimental area of 8×3 cm on the back of the guinea pigs. The animals were divided into the following groups: Normal control group (NC), low-dose laser treatment group (L-LS), high-dose laser treatment group (H-LS), and Q-switched Nd:YAG treatment group (QC)...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#14
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#15
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28427999/serpinb1-ameliorates-acute-lung-injury-in-liver-transplantation-through-erk1-2-mediated-stat3-dependent-ho-1-induction
#16
Weifeng Yao, Haobo Li, Gangjian Luo, Xiang Li, Chaojin Chen, Dongdong Yuan, Xinjin Chi, Zhengyuan Xia, Ziqing Hei
BACKGROUND: Postoperative acute lung injury(ALI) is a severe complication after liver transplantation, which severely affects postoperative patients' survival. The underlying mechanism is largely unknown and effective treatment limited. We explored the role of serpin protease inhibitor B1(SERPINB1), a potent inhibitor of neutrophil serine proteases, in ALI in liver transplantation and its interplay with signal transducer and activator of transcription 3(STAT3) and heme oxygenase-1(HO-1)...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28427893/study-of-acetylcholinesterase-activity-and-apoptosis-in-sh-sy5y-cells-and-mice-exposed-to-ethanol
#17
Wenjun Sun, Liangjing Chen, Wei Zheng, Xiaoan Wei, Wenqi Wu, Ellen G Duysen, Wei Jiang
Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol...
April 17, 2017: Toxicology
https://www.readbyqxmd.com/read/28427235/catan-ionic-hybrid-lipidic-nano-carriers-for-enhanced-bioavailability-and-anti-tumor-efficacy-of-chemodrugs
#18
Bilin Liu, Dan He, Jianyong Wu, Quan Sun, Mi Zhang, Qunyou Tan, Yao Li, Jingqing Zhang
To date there has not been any report on catan-ionic hybrid lipidic nano-carriers, let alone a report on applying them to deliver insoluble anti-tumor drugs. Catan-ionic hybrid lipidic nano-carriers containing curcumin (CUR-C-HLN) inherit the merits of catan-ionic systems, hybrid lipidic systems and nano-structured carriers (the second-generation substitute of solid lipidic nano-systems). Catan-ionic surfactants increased microvesicle stabilization by producing unordered isometric clusters, enhanced absorptive amount as an inhibitor of enzyme and protein, improved tumor accumulation by cellular endocytosis and membranous fusion; hybrid lipids helped to obtain high drug content and low leakage by forming a less-organized matrix arrangement...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427225/enhancing-synthetic-lethality-of-parp-inhibitor-and-cisplatin-in-brca-proficient-tumour-cells-with-hyperthermia
#19
Arlene L Oei, Caspar M van Leeuwen, Vidhula R Ahire, Hans M Rodermond, Rosemarie Ten Cate, Anneke M Westermann, Lukas J A Stalpers, Johannes Crezee, H Petra Kok, Przemek M Krawczyk, Roland Kanaar, Nicolaas A P Franken
BACKGROUND: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427210/dependence-of-p53-deficient-cells-on-the-dhx9-dexh-box-helicase
#20
Teresa Lee, Jerry Pelletier
DHX9 is a DExH-box helicase family member with key regulatory roles in a broad range of cellular processes. It participates at multiple levels of gene regulation, including DNA replication, transcription, translation, RNA transport, and microRNA processing. It has been implicated in tumorigenesis and recent evidence suggests that it may be a promising chemotherapeutic target. Previous studies have determined that DHX9 suppression elicits an apoptotic or senescence response by activating p53 signaling. Here, we show that DHX9 inhibition can also have deleterious effects in cells lacking functional p53...
March 3, 2017: Oncotarget
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