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https://www.readbyqxmd.com/read/29679654/the-vanillin-derivative-6-bromine-5-hydroxy-4-methoxybenzaldehyde-induces-aberrant-mitotic-progression-and-enhances-radio-sensitivity-accompanying-suppression-the-expression-of-plk1-in-esophageal-squamous-cell-carcinoma
#1
Meng-Meng Gu, Ming Li, Dexuan Gao, Lang-Huan Liu, Yue Lang, Si-Ming Yang, Hongling Ou, Bo Huang, Ping-Kun Zhou, Zeng-Fu Shang
Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase...
April 18, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29679549/chm-1-a-novel-microtubule-destabilizing-agent-exhibits-antitumor-activity-via-inducing-the-expression-of-sirt2-in-human-breast-cancer-cells
#2
Chin-Wei Liu, Ying-Chao Lin, Chao-Ming Hung, Bing-Lan Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way, Chih-Hsin Hung
Breast cancer is a major public health problem throughout the world. In this report, we investigated whether CHM-1, a novel synthetic antimitotic agent could be developed into a potent antitumor agent for treating human breast cancer. CHM-1 induced growth inhibition in MDA-MB-231, MDA-MB-453 and MCF-7 cells in a concentration-dependent manner. Importantly, CHM-1 is less toxic to normal breast (HBL-100) cells. CHM-1 interacted with tubulin, markedly inhibited tubulin polymerization, and disrupted microtubule organization...
April 18, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29679546/lithium-chloride-licl-induced-autophagy-and-downregulated-expression-of-transforming-growth-factor-%C3%AE-induced-protein-tgfbi-in-granular-corneal-dystrophy
#3
Danyao Nie, Yun Peng, Ming Li, Xinhua Liu, Meilan Zhu, Lin Ye
This study evaluated whether lithium chloride (LiCl) prevents cytoplasmic accumulation of mutant-transforming growth factor β-induced protein (Mut-TGFBI) in granular corneal dystrophy (GCD) via activation of the autophagy pathway. Levels of TGFBI and microtubule-associated protein 1A/1B-light chain 3 (LC3) in 3 GCD patients and healthy controls were analyzed by immunohistochemistry (IHC) staining and Western blot. Primary corneal fibroblasts were isolated and transfected with wild type or mutant type TGFBI over-expressed vectors, and then treated with LiCl and/or autophagy inhibitor 3-methyladenine (3-MA)...
April 18, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29679350/alleviation-mechanisms-of-selenium-on-cadmium-spiked-in-chicken-ovarian-tissue-perspectives-from-autophagy-and-energy-metabolism
#4
Shuang Wang, Zhe Xu, Hang Yin, Yahong Min, Shu Li
Cadmium (Cd) is a kind of toxic heavy metal and it can cause damage to organs and tissues. Selenium (Se) can antagonize some metal element toxicity including Cd. The present study was designed to investigate Cd-induced damage to chicken ovary by autophagy and the protective mechanism of Se on Cd-induced damage. Administration of Cd for 12 weeks led to energy metabolism disorder of the chicken ovarian tissues, which resulted in autophagy. In addition, the mRNA expression of glucose-related genes including hexokinase II (HK2), pyruvate kinase (PK), pyruvate dehydrogenase complex (PDHX), and succinate dehydrogenase (SDH) and the activities of ATPase, including Na+ -K+ -ATPase, Ca2+ -ATPase, Mg2+ -ATPase, were all downregulated remarkably compared with the control...
April 21, 2018: Biological Trace Element Research
https://www.readbyqxmd.com/read/29679050/misp-regulates-the-iqgap1-cdc42-complex-to-collectively-orchestrate-spindle-orientation-and-mitotic-progression
#5
Barbara Vodicska, Berati Cerikan, Elmar Schiebel, Ingrid Hoffmann
Precise mitotic spindle orientation is essential for both cell fate and tissue organization while defects in this process are associated with tumorigenesis and other diseases. In most animal cell types, the dynein motor complex is anchored at the cell cortex and exerts pulling forces on astral microtubules to position the spindle. The actin-binding protein MISP controls spindle orientation and mitotic progression in human cells. However, the exact underlying mechanism remains to be elucidated. Here we report that MISP interacts with the multidomain scaffolding protein IQGAP1...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29678463/design-synthesis-and-antineoplastic-activity-of-novel-hybrids-of-podophyllotoxin-and-indirubin-against-human-leukaemia-cancer-cells-as-multifunctional-anti-mdr-agents
#6
Jing Wang, Li Long, Yongzheng Chen, Yingshu Xu, Lei Zhang
To overcome cancer drug resistance, in present study, a series of podophyllotoxin-indirubin hybrids were designed, synthesized, and evaluated for anticancer efficacy against two human chronic myeloid leukemia cell cultures. Among them, compound Da-1 was the most potent in resistent K562/VCR cells with an IC50 value of 0.076 ± 0.008 μM. Preliminary mechanism studies showed that Da-1 significantly induced apoptosis and cell cycle arrest at the G2 phase. Decrease in mitochondrial membrane potential, accompanied by activated PARP cleavage, was observed in K562/VCR cells after incubation with Da-1...
April 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29677125/detrimental-effects-of-helium-ion-irradiation-on-cognitive-performance-and-cortical-levels-of-map-2-in-b6d2f1-mice
#7
Jacob Raber, Eileen Ruth S Torres, Tunde Akinyeke, Joanne Lee, Sydney J Weber Boutros, Mitchell S Turker, Amy Kronenberg
The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not...
April 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29676087/-anti-breast-cancer-mechanism-of-flavonoids
#8
REVIEW
Bai-Bing Pang, Yuan-Kui Chu, Hua Yang
Flavonoids are a kind of ubiquitous natural products in plants and essential active ingredients of many medicinal plants. They have the characteristics of broad biological activity, high efficiency and low toxicity, with good prevention and cure effects on various types of tumors. Breast cancer is the commonest cancer disease and the main cause of cancer death in women worldwide. In China, the morbidity and mortality are still on the rise. Flavonoids can inhibit the occurrence and development of breast cancer in various aspects...
March 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29675785/neuronal-autophagy-and-axon-degeneration
#9
REVIEW
Yu Wang, Mingxue Song, Fuyong Song
Axon degeneration is a pathophysiological process of axonal dying and breakdown, which is characterized by several morphological features including the accumulation of axoplasmic organelles, disassembly of microtubules, and fragmentation of the axonal cytoskeleton. Autophagy, a highly conserved lysosomal-degradation machinery responsible for the control of cellular protein quality, is widely believed to be essential for the maintenance of axonal homeostasis in neurons. In recent years, more and more evidence suggests that dysfunctional autophagy is associated with axonal degeneration in many neurodegenerative diseases...
April 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29674711/microtubule-dynamics-an-interplay-of-biochemistry-and-mechanics
#10
REVIEW
Gary J Brouhard, Luke M Rice
Microtubules are dynamic polymers of αβ-tubulin that are essential for intracellular organization, organelle trafficking and chromosome segregation. Microtubule growth and shrinkage occur via addition and loss of αβ-tubulin subunits, which are biochemical processes. Dynamic microtubules can also engage in mechanical processes, such as exerting forces by pushing or pulling against a load. Recent advances at the intersection of biochemistry and mechanics have revealed the existence of multiple conformations of αβ-tubulin subunits and their central role in dictating the mechanisms of microtubule dynamics and force generation...
April 19, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29673981/synthesis-and-evaluation-of-new-2-chloro-4-aminopyrimidine-and-2-6-dimethyl-4-aminopyrimidine-derivatives-as-tubulin-polymerization-inhibitors
#11
Shaoyu Xu, Baijiao An, Yuxin Li, Xunbang Luo, Xingshu Li, Xian Jia
Eighteen new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives were synthesized and evaluated as tubulin polymerization inhibitor for the treatment of cancer. Among them, compounds 10, 17, 20 and 21 exhibited potent antiproliferative activities against five human cancer cell lines. Microtubule dynamics assay showed that compound 17 could effectively inhibit tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. Further mechanism studies revealed that 17 could induce G2/M phase arrest, disrupt the organization of the cellular microtubule network and induce cell apoptosis and mitochondrial dysfunction...
April 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29673913/epothilone-d-inhibits-microglia-mediated-spread-of-alpha-synuclein-aggregates
#12
Dario Valdinocci, Gary Grant, Tracey Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29673238/association-of-exercise-induced-autophagy-upregulation-and-apoptosis-suppression-with-neuroprotection-against-pharmacologically-induced-parkinson-s-disease
#13
Yong Chul Jang, Dong Joo Hwang, Jung Hoon Koo, Hyun Seob Um, Nam Hee Lee, Dong Cheol Yeom, Youngil Lee, Joon Yong Cho
PURPOSE: We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD). METHODS: PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10)...
March 30, 2018: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/29673078/crispr-cas9-mediated-gfp-knock-in-at-the-map1lc3b-locus-in-293ft-cells-is-better-for-bona-fide-monitoring-cellular-autophagy
#14
Zhiqiang Wu, Jinlin Zhao, Minghan Qiu, Zeyun Mi, Maobin Meng, Yu Guo, Hui Wang, Zhiyong Yuan
Accurately identifying and quantifying cellular autophagy is very important as the significance of autophagy in physiological and pathological processes becomes increasingly evident. Ectopically expressed fluorescent-tagged microtubule-associated protein light chain 3B (MAP1LC3B, LC3) is the most widely used reporter for monitoring autophagy activity thus far. However, this approach ignored the influence of constitutively overexpressed LC3 on autophagy itself and autophagy-related processes and its accuracy in indicating autophagy is questionable...
April 19, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29672318/a-novel-2-methoxyestradiol-analogue-is-responsible-for-vesicle-disruption-and-lysosome-aggregation-in-breast-cancer-cells
#15
Sandra D Nkandeu, Iman van den Bout, Marianne J Cronjé, Dirk H van Papendorp, Anna M Joubert
BACKGROUND: 2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17-β-estradiol with anti-proliferative and anti-angiogenic properties. Due to 2ME2's rapid metabolism and low oral bioavailability in in vivo settings, 2ME2 analogues have been designed to alleviate these issues. One of these compounds is 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). A previous work alluded to the ability of ESE-16 to induce autophagic cell death. Therefore, we investigated the mode of action of ESE-16 by studying its effects on autophagy, vesicle formation, and lysosomal organisation...
April 19, 2018: Pharmacology
https://www.readbyqxmd.com/read/29671923/sucrose-assists-selection-of-high-quality-oocytes-in-pigs
#16
Thanh Quang Dang-Nguyen, Hiep Thi Nguyen, Tamas Somfai, David Wells, Nguyen Thi Men, Nguyen Viet-Linh, Junko Noguchi, Hiroyuki Kaneko, Kazuhiro Kikuchi, Takashi Nagai
We investigated whether high-quality in vitro matured (IVM) oocytes can be distinguished from poor ones based on the morphological changes after treatment with hyperosmotic medium containing 0.2 mol/L sucrose in pigs. We hypothesize that IVM oocytes maintaining round shape have higher quality than mis-shapened oocytes following dehydration. Oocyte quality was verified by determining embryonic developmental competence using in vitro fertilization, nuclear transfer and parthenogenetic activation. In all cases, the round oocytes had greater (p < ...
April 19, 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/29671277/reduced-adrenomedullin-parallels-microtubule-dismantlement-in-frontotemporal-lobar-degeneration
#17
Hilda Ferrero, Ignacio M Larrayoz, Maite Solas, Alfredo Martínez, María J Ramírez, Francisco J Gil-Bea
Tau is a microtubule-associated protein highly expressed in neurons with a chief role in microtubule dynamics and axonal maintenance. Adrenomedullin gene (ADM) codifies for various peptides that exert broad range of actions in the body. Previous works in our groups have shown that increased ADM products are positively correlated to microtubule disruption and tau pathology in Alzheimer's disease brains. In the present study, we explore the involvement of ADM in the neuropathology of frontotemporal lobar degeneration that presents with primary tauopathy (FTLD-tau)...
April 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29670958/large-scale-chirality-in-an-active-layer-of-microtubules-and-kinesin-motor-proteins
#18
Kyongwan Kim, Natsuhiko Yoshinaga, Sanjib Bhattacharyya, Hikaru Nakazawa, Mitsuo Umetsu, Winfried Teizer
During the early developmental process of organisms, the formation of left-right laterality requires a subtle mechanism, as it is associated with other principal body axes. Any inherent chiral feature in an egg cell can in principal trigger this spontaneous breaking of chiral symmetry. Individual microtubules, major cytoskeletal filaments, are known as chiral objects. However, to date there lacks convincing evidence of a hierarchical connection of the molecular nature of microtubules to large-scale chirality, particularly at the length scale of an entire cell...
April 19, 2018: Soft Matter
https://www.readbyqxmd.com/read/29670132/tau-antibody-structure-reveals-a-molecular-switch-defining-a-pathological-conformation-of-the-tau-protein
#19
Jessica E Chukwu, Jan T Pedersen, Lars Ø Pedersen, Christiane Volbracht, Einar M Sigurdsson, Xiang-Peng Kong
Tau antibodies have shown therapeutic potential for Alzheimer's disease and several are in clinical trials. As a microtubule-associated protein, tau relies on dynamic phosphorylation for its normal functions. In tauopathies, it becomes hyperphosphorylated and aggregates into toxic assemblies, which collectively lead to neurodegeneration. Of the phospho-epitopes, the region around Ser396 has received particular attention because of its prominence and stability in tauopathies. Here we report the first structure of a monoclonal tau antibody in complex with the pathologically important phospho-Ser396 residue...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670107/inhibition-of-cancer-progression-by-a-novel-trans-stilbene-derivative-through-disruption-of-microtubule-dynamics-driving-g2-m-arrest-and-p53-dependent-apoptosis
#20
Pravat Kumar Parida, Barun Mahata, Abhisek Santra, Sohini Chakraborty, Zhumur Ghosh, Sanghamitra Raha, Anup Kumar Misra, Kaushik Biswas, Kuladip Jana
Resveratrol, a trans-stilbene polyphenolic compound and its synthetic analogs are widely used bioactive molecules due to their remarkable chemo-preventive potential. Here, we have identified a novel synthetic trans-stilbene compound, Z-DAN-11 ((Z)-3-(3, 4-dimethoxyphenyl)-2-(3, 4, 5-trimethoxyphenyl) acrylonitrile) which shows remarkable efficacy in blocking tumor growth and progression both in vitro and in vivo. Z-DAN-11 inhibits proliferation of cancer cells in vitro through microtubule depolymerization that induced G2/M arrest and consequently leads to apoptotic cell death...
April 18, 2018: Cell Death & Disease
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