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arrested development

Kolla Rajasekhar, Kapilkumar Mehta, Thimmaiah Govindaraju
Amyloid beta (Aβ) aggregation is the key trait responsible for the pathological devastation caused by Alzheimer's disease (AD). Among the various pathways of multifaceted toxicity exhibited by Aβ aggregates in neuronal cells, generation of reactive oxygen species (ROS) by Aβ-CuII complex and mitochondrial damage are prominent. Aβ interferes with mitochondrial transport channels, causing mitochondrial dysfunction. Herein, we present nontoxic hybrid multifunctional modulators (HMMs, TGR86-88) developed by integrating the structural and functional features of the metal chelating aggregation modulator, clioquinol (Clq) and the antioxidant epigallocatechin gallate (EGCG)...
March 20, 2018: ACS Chemical Neuroscience
Qianjun Li, Gang Ma, Huimin Guo, Suhua Sun, Ying Xu, Bingjian Wang
BACKGROUND AND AIMS: Down-regulation of the growth arrest specific transcript 5 (GAS5) (long non-coding RNA) is associated with cell proliferation of gastric cancer (GC) and a poor prognosis. We aimed to investigate whether the variant rs145204276 of GAS5 is associated with the prognosis of GC in the Chinese population, and to unveil the regulatory mechanism underlying the GAS5 expression in GC tissues. METHOD: 1,253 GC patients and 1,354 healthy controls were included...
March 2018: Journal of Gastrointestinal and Liver Diseases: JGLD
Goro Katsuumi, Ippei Shimizu, Yohko Yoshida, Tohru Minamino
In mammals, aging is associated with accumulation of senescent cells. Stresses such as telomere shortening and reactive oxygen species induce "cellular senescence", which is characterized by growth arrest and alteration of the gene expression profile. Chronological aging is associated with development of age-related diseases, including heart failure, diabetes, and atherosclerotic disease, and studies have shown that accumulation of senescent cells has a causative role in the pathology of these age-related disorders...
2018: Frontiers in Cardiovascular Medicine
Fei Yan, Yu Sun, Yang Mao, Meiying Wu, Zhiting Deng, Shuai Li, Xin Liu, Li Xue, Hairong Zheng
Cardiovascular diseases resulting from atherosclerosis have become a serious threat to human health. It is well-known that an ongoing inflammatory response is involved during atherosclerosis progression that ultimately results in the accumulation of lipids and formation of plaques. Monitoring the pathological changes during the inflammatory response will be of great significance for early diagnosis and therapeutic evaluation of atherosclerosis. Targeted contrast-enhanced ultrasonography has been shown to be a promising noninvasive imaging technique for evaluating the degree of atherosclerosis and may potentially be translated to clinical imaging in the future...
2018: Theranostics
Piya Ghose, Alina Rashid, Peter Insley, Meera Trivedi, Pavak Shah, Anupriya Singhal, Yun Lu, Zhirong Bao, Shai Shaham
Phagocytosis of dying cells is critical in development and immunity1-3 . Although proteins for recognition and engulfment of cellular debris following cell death are known4,5 , proteins that directly mediate phagosome sealing are uncharacterized. Furthermore, whether all phagocytic targets are cleared using the same machinery is unclear. Degeneration of morphologically complex cells, such as neurons, glia and melanocytes, produces phagocytic targets of various shapes and sizes located in different microenvironments6,7 ...
March 19, 2018: Nature Cell Biology
Kaori Wakabayashi, Takahiko Umahara, Katsuiku Hirokawa, Haruo Hanyu, Toshiki Uchihara
α-Synuclein shares structural homology with 14-3-3 proteins. Seven 14-3-3 protein isoforms have been identified in mammals. Among them, the 14-3-3 sigma isoform was initially considered absent in the mammalian brain. However, we previously identified immunohistochemical association of 14-3-3 sigma with Pick bodies. Because 14-3-3 isoforms other than sigma isoform have been identified in Lewy bodies, we were prompted to look for this 14-3-3 sigma-like immunoreactivity (IR) in Lewy bodies in the brainstem, cerebral cortex, and Lewy neurites in seven patients with Lewy body disease...
March 16, 2018: Neuroscience Letters
Yan Wang, Wenbin Xu, Zixun Yan, Weili Zhao, Jianqing Mi, Junmin Li, Hua Yan
BACKGROUND: Metformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-tumor effects in many cancers, including multiple myeloma (MM); however, the underlying molecular mechanisms have not been clearly elucidated. METHODS: The anti-myeloma effects of metformin were evaluated using human MM cell lines (RPMI8226 and U266) in vitro and in vivo NOD-SCID murine xenograft MM model. Cell viability was assessed with CCK8 and cell proliferation was measured by EdU incorporation assay...
March 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
Vincent Auffret, Yves Cottin, Guillaume Leurent, Martine Gilard, Jean-Claude Beer, Amer Zabalawi, Frédéric Chagué, Emanuelle Filippi, Damien Brunet, Jean-Philippe Hacot, Philippe Brunel, Mourad Mejri, Luc Lorgis, Gilles Rouault, Philippes Druelles, Jean-Christophe Cornily, Romain Didier, Emilie Bot, Bertrand Boulanger, Isabelle Coudert, Aurélie Loirat, Marc Bedossa, Dominique Boulmier, Maud Maza, Marielle Le Guellec, Rishi Puri, Marianne Zeller, Hervé Le Breton
Aims: To derive and validate a readily useable risk score to identify patients at high-risk of in-hospital ST-segment elevation myocardial infarction (STEMI)-related cardiogenic shock (CS). Methods and results: In all, 6838 patients without CS on admission and treated by primary percutaneous coronary intervention (pPCI), included in the Observatoire Régional Breton sur l'Infarctus (ORBI), served as a derivation cohort, and 2208 patients included in the obseRvatoire des Infarctus de Côte-d'Or (RICO) constituted the external validation cohort...
March 15, 2018: European Heart Journal
Min Su, Heran Wang, Wenxiang Wang, Ying Wang, Linda Ouyang, Chen Pan, Longzheng Xia, Deliang Cao, Qianjin Liao
In order to maintain integrity of the genome, eukaryotic cells develop a complex DNA damage/repair response network, which can induce cell cycle arrest, apoptosis, or DNA repair. Chemo- and radiation therapies, which act primarily through the induction of DNA damage, are the most commonly used therapies for cancer. Impairment in the DNA damage response and repair system that protect cells from persistent DNA damage can affect the therapeutic efficacy of cancer. To date, accumulating evidence has suggested that long non-coding RNAs (lncRNAs) are involved in the regulation of the DNA damage/repair network...
March 15, 2018: Acta Biochimica et Biophysica Sinica
Michail Mitsis, George A Alexiou, Evrysthenis Vartholomatos, Georgios Markopoulos, Diamanto Lazari, Entela Hodaj, Dimitrios Nastos, Panagiota Zagorianakou, Vasiliki Galani, Athanasios P Kyritsis
PURPOSE: Breast cancer is the most commonly diagnosed malignancy among women. Breast cancer cells may develop resistance to current chemotherapy, thus new chemotherapeutic agents are urgently needed. METHODS: A major number of drugs with anticancer activity have been isolated from plants. Herewith, we investigated for the first time the effect of N-(p-coumaroyl) serotonin (CS), isolated from Centaurea seed on a drug-resistant breast carcinoma (MCF-7) cells. Viability and proliferation of the cells were examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
JinYing Liu, Xiaokang Liu, Wei Ma, Wei Kou, CaiLi Li, Jin Zhao
PURPOSE: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells. METHODS: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Wei Pang, Fu-Zhi Lian, Xue Leng, Shu-Min Wang, Yi-Bo Li, Zi-Yu Wang, Kai-Ren Li, Zhi-Xian Gao, Yu-Gang Jiang
A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151 differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis, injury, and neuroinflammation responses...
March 18, 2018: Environmental Science and Pollution Research International
Cheng-Fu Cai, Li-Man Liu, Han-Jing Shangguan, Cun-Shan Liu, Xian-Yang Luo, Yi-Meng Li
The Wnt/β-catenin pathway serves important roles in cancer development. The expression and function of Chibby (Cby), as a direct antagonist of β-catenin, in nasopharyngeal carcinoma (NPC) has not been fully investigated. The present study revealed that the mRNA and protein expression of Cby was significantly lower in NPC tissue than in the adjacent normal tissue. Low expression of Cby was significantly associated with the tumor and the clinical staging. Furthermore, Cby overexpression inhibited the proliferation of human NPC SUNE1 cells and induced cell cycle arrest...
April 2018: Oncology Letters
Douglas A Salguero, Pamela A Barletta, Willaim Sierraalta
BACKGROUND: Multiple myeloma is a hematologic disease with high mortality rates all over the world. The diagnosis has always been challenging since the first case was reported in 1844. For that reason the diagnostic criteria have evolved over years to include the features of the disease more comprehensively. Unusual presentations are infrequent and a diagnostic challenge. For this reason we report this rare case in which diarrhea and abdominal pain were the initial presenting symptoms of multiple myeloma with a plasmacytoma...
March 18, 2018: Journal of Medical Case Reports
Marcus J G W Ladds, Ingeborg M M van Leeuwen, Catherine J Drummond, Su Chu, Alan R Healy, Gergana Popova, Andrés Pastor Fernández, Tanzina Mollick, Suhas Darekar, Saikiran K Sedimbi, Marta Nekulova, Marijke C C Sachweh, Johanna Campbell, Maureen Higgins, Chloe Tuck, Mihaela Popa, Mireia Mayoral Safont, Pascal Gelebart, Zinayida Fandalyuk, Alastair M Thompson, Richard Svensson, Anna-Lena Gustavsson, Lars Johansson, Katarina Färnegårdh, Ulrika Yngve, Aljona Saleh, Martin Haraldsson, Agathe C A D'Hollander, Marcela Franco, Yan Zhao, Maria Håkansson, Björn Walse, Karin Larsson, Emma M Peat, Vicent Pelechano, John Lunec, Borivoj Vojtesek, Mar Carmena, William C Earnshaw, Anna R McCarthy, Nicholas J Westwood, Marie Arsenian-Henriksson, David P Lane, Ravi Bhatia, Emmet McCormack, Sonia Laín
The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex...
March 16, 2018: Nature Communications
A R Niemeijer
Phyllosilicate-bearing faults are characterized by an anastomosing foliation with intervening hard clasts and are believed to be long-term weak structures. Here, I present results of sliding experiments on gouges of 80 wt% quartz and 20 wt% muscovite, sheared under hydrothermal conditions at constant velocity. The results show that significant strengthening occurs over a narrow range of sliding velocities (0.03-1 μm/s). At the lowest velocity investigated, weakness is achieved after a considerable sliding distance of over 20 mm with friction reaching a value of 0...
March 16, 2018: Scientific Reports
M Boutsikou, D Shore, W Li, M Rubens, A Pijuan, M A Gatzoulis, S Babu-Narayan
INTRODUCTION: The diagnosis of ALCAPA syndrome is sporadic in adulthood, of the limited cases in the literature most are incidental or without symptoms. There is a broad spectrum of clinical manifestations of ALCAPA syndrome however, including sudden cardiac death. CASES: We present herewith a series of 12 consecutive patients with ALCAPA, all diagnosed in adulthood (between 18 and 73 years of age). Five patients developed symptoms (breathlessness) after the fourth decade of life, 3 were undiagnosed despite a history of previous mitral valve repair, one presented with heart failure, one with resuscitated cardiac arrest, whereas two patients were asymptomatic...
February 24, 2018: International Journal of Cardiology
Zhili Wan, Yingen Sun, Lulu Ma, Feibai Zhou, Jian Guo, Song-Qing Hu, Xiao-Quan Yang
Nanofibrils from self-assembly of the naturally occurring saponin glycyrrhizic acid (GA) can be used to create an oil-in-water emulsion foam with long-term stability. Through a homogenization and aeration followed by a rapid cooling, stable emulsion foams can be produced from the mixtures of sunflower oil and saponin nanofibrils. At high temperature, the GA fibrils form a multilayer assembly at the interface, creating an interfacial fibrillar network to stabilize the oil droplets and air bubbles generated during homogenization...
March 16, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Olivier Turc, François Tardieu
Abortion of reproductive organs is a major limiting factor of yield under water deficit, but is also a trait selected for by evolutionary processes. Youngest reproductive organs must be prone to abortion so older organs can finish their development in case of limited resources. Water deficit increases natural abortion via two developmentally-driven processes, namely a signal from the first fertilized ovaries and a simultaneous arrest of the expansive growth of all ovaries at a precise stage. In maize (Zea mays) subjected to water deficits typically encountered in dryland agriculture, these developmental mechanisms account for 90 % of drought-associated abortion and are irreversible three days after silk emergence...
March 13, 2018: Journal of Experimental Botany
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
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