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https://www.readbyqxmd.com/read/28969571/synthesis-%C3%AE-catenin-translocation-capability-and-alp-activation-activity-of-7h-thiazolo-3-2-b-1-2-4-triazin-7-one-derivatives
#1
Shicheng Hou, Henan Xu, Jianshu Hu, Jian Hou, Yan Wang, Zhe Jin, David C C Wan, Chun Hu
Background Osteoporosis (OP) is a common bone disease, most often diagnosed in post-menopausal women. The majority of OP treatments focused at manipulation of the patient's hormone levels, therefore, they are associated with significant adverse effects. Objective To design, synthesize and evaluate the β-catenin translocation capability and the alkaline phosphatase (ALP) activation activity of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives. Method The styrene derivatives were synthesized as raw materials, followed by oxidation and condensation reactions, 6-aryl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one derivatives (1) were obtained...
October 2, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28964605/atm-signals-to-ampk-to-promote-autophagy-and-positively-regulate-dna-damage-in-response-to-cadmium-induced-ros-in-mouse-spermatocytes
#2
Renyan Li, Xue Luo, Yijian Zhu, Letian Zhao, Lianbing Li, Qiang Peng, Mingfu Ma, Yanfei Gao
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined...
September 27, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28963502/epithelial-chloride-transport-by-cftr-requires-tmem16a
#3
Roberta Benedetto, Jiraporn Ousingsawat, Podchanart Wanitchakool, Yong Zhang, Michael J Holtzman, Margarida Amaral, Jason R Rock, Rainer Schreiber, Karl Kunzelmann
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in airways and intestine that is activated through ATP binding and phosphorylation by protein kinase A, but fails to operate in cystic fibrosis (CF). TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca(2+) activated secretory chloride channel independent of CFTR. Here we report that tissue specific knockout of the TMEM16A gene in mouse intestine and airways not only eliminates Ca(2+)-activated Cl(-) currents, but unexpectedly also abrogates CFTR-mediated Cl(-) secretion and completely abolishes cAMP-activated whole cell currents...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28956246/hematological-biochemical-and-histopathological-impacts-of-barium-chloride-and-barium-carbonate-accumulation-in-soft-tissues-of-male-sprague-dawley-rats
#4
Amany Tharwat Mohammed, Hager Tarek H Ismail
The present study was designed to investigate the hematotoxicity, sero-biochemical and histological changes due to the accumulation of BaCl2 and BaCO3, the most important barium salts in our daily lives, in different soft tissues including the liver, kidney, heart, and spleen of adult rats after an oral exposure for 30 consecutive days, and to explain the different mechanisms by which this metal can exert these impacts. For this purpose, adult male rats were divided into three main groups of 15 animals each: group I, serving as controls, group II, receiving BaCl2 orally in a dose of 179 mg barium/kg b...
September 27, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28930854/a-female-patient-with-hypokalaemia-induced-j-wave-syndrome-an-unusual-case-report
#5
Aqian Wang, Xiang Li, Muhammad Nabeel Dookhun, Tiancheng Zhang, Ping Xie, Yunshan Cao
RATIONALE: Prominent J waves can be seen in life-threatening cardiac arrhythmias such as Brugada syndrome, early repolarization syndrome, and ventricular fibrillation. We herein present an unusual case report of hypokalemia-induced J wave syndrome and ST (a part of ECG) segment elevation. PATIENTS CONCERNS: A 52-year-old woman with chief complaints of chest pain for 2 hours and diarrhea showed a marked hypokalemia (2.8 mmol/L) and slightly elevated creatine kinase-MB (CK-MB) (57...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28929374/inhibition-of-gsk-3%C3%AE-activation-protects-sd-rat-retina-against-n-methyl-n-nitrosourea-induced-degeneration-by-modulating-the-wnt-%C3%AE-catenin-signaling-pathway
#6
Baoying Wang, Chenghu Hu, Xiaobei Yang, Fangying Du, Yan Feng, Hongbo Li, Chunhui Zhu, Xiaorui Yu
Retinal degenerative diseases are characterized by photoreceptor cell loss. Photoreceptor cell loss leading to retinal degeneration can be induced by N-methyl-N-nitrosourea (MNU), which was widely used to mimic the pathology. However, the mechanism by which MNU induces photoreceptor cell loss is still largely unknown. The purpose of the present study was to investigate whether phosphorylation of glycogen synthase kinase-3β (p-GSK-3β) is a potent mediator of MNU-induced retinal degeneration and how p-GSK-3β affects the process...
September 19, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28924007/multiple-signaling-pathways-coordinately-regulate-forgetting-of-olfactory-adaptation-through-control-of-sensory-responses-in-c-elegans
#7
Tomohiro Kitazono, Sayuri Hara-Kuge, Osamu Matsuda, Akitoshi Inoue, Manabi Fujiwara, Takeshi Ishihara
Forgetting memories is important for animals to properly respond to continuously changing environments. To elucidate the mechanisms of forgetting, we used one of the behavioral plasticities of C. elegans hermaphrodite, olfactory adaptation to an attractive odorant, diacetyl, as a simple model of learning. In C. elegans, the TIR-1/JNK-1 pathway accelerates forgetting of olfactory adaptation by facilitating neural secretion from AWC sensory neurons. In this study, to identify the downstream effectors of the TIR-1/JNK-1 pathway, we conducted a genetic screen for suppressors of the gain-of-function mutant of tir-1 (ok1052), which shows excessive forgetting...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923355/in-vitro-anticancer-activity-of-new-gold-iii-porphyrin-complexes-in-colon-cancer-cells
#8
Fatima Dandash, David Yannick Léger, Chloë Fidanzi-Dugas, Soumaya Nasri, Frédérique Brégier, Robert Granet, Walid Karam, Mona Diab-Assaf, Vincent Sol, Bertrand Liagre
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide. The limitations of cisplatin-based chemotherapy have prompted intense interest among scientists to search for alternative metal-based anticancer medicines. Gold(III) complexes have been among the most widely investigated since they showed higher cytotoxicity than cisplatin and promising in vitro and in vivo anticancer activities in CRC but their clinical usefulness has been limited by their poor stability under physiological conditions...
September 6, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28920462/involvement-of-atrial-natriuretic-peptide-in-abrogated-cardioprotective-effect-of-ischemic-preconditioning-in-ovariectomized-rat-heart
#9
V K Vishwakarma, A Goyal, J K Gupta, P K Upadhyay, H N Yadav
BACKGROUND: Nitric oxide (NO) is an effective mediator of ischemic preconditioning (IPC)-induced cardioprotection. Atrial natriuretic peptide (ANP) is downregulated after ovariectomy, which results in reduction in the level of NO. The present study deals with the investigation of the role of ANP in abrogated cardioprotective effect of IPC in the ovariectomized rat heart. METHODS: Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min of ischemia and 120 min of reperfusion...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28911173/lithium-chloride-increases-cox-2-expression-and-pge2-production-in-a-human-granulosa-lutein-svog-cell-line-via-a-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway
#10
Long Bai, Hsun-Ming Chang, Jung-Chien Cheng, Guiyan Chu, Peter C K Leung, Gongshe Yang
Lithium chloride (LiCl) is widely prescribed for the treatment of bipolar disorders and is associated with a higher incidence of reproductive adverse effects. Cyclooxygenase (COX)-2 and its derivative, prostaglandin E2 (PGE2), play regulatory roles in the human ovulatory process. Whether LiCl affects ovulation by regulating COX2 expression and PGE2 production in the human ovary is still largely unknown. The aim of this study was to investigate the effect of LiCl on the expression of COX-2 and production of PGE2 in human granulosa-lutein (hGL) cells, as well as the mechanisms underlying this effect...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28893247/cell-specific-mechanisms-of-tmem16a-ca-2-activated-chloride-channel-in-cancer
#11
REVIEW
Hui Wang, Liang Zou, Ke Ma, Jiankun Yu, Huizhe Wu, Minjie Wei, Qinghuan Xiao
TMEM16A (known as anoctamin 1) Ca(2+)-activated chloride channel is overexpressed in many tumors. TMEM16A overexpression can be caused by gene amplification in many tumors harboring 11q13 amplification. TMEM16A expression is also controlled in many cancer cells via transcriptional regulation, epigenetic regulation and microRNAs. In addition, TMEM16A activates different signaling pathways in different cancers, e.g. the EGFR and CAMKII signaling in breast cancer, the p38 and ERK1/2 signaling in hepatoma, the Ras-Raf-MEK-ERK1/2 signaling in head and neck squamous cell carcinoma and bladder cancer, and the NFκB signaling in glioma...
September 11, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#12
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
November 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28886972/benzene-metabolite-hydroquinone-induces-apoptosis-of-bone-marrow-mononuclear-cells-through-inhibition-of-%C3%AE-catenin-signaling
#13
Jiaqi Li, Songfu Jiang, Yi Chen, Ruye Ma, Jingjing Chen, Shanhu Qian, Yifen Shi, Yixiang Han, Shenghui Zhang, Kang Yu
The Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway has been shown to play an important role in hematopoiesis, and hematopoietic cells are sensitive targets for benzene-induced hematotoxicity. We therefore hypothesized that dysregulation of the Akt/GSK-3β/β-catenin signaling was associated with benzene-induced hematotoxicity. Here, we showed that hydroquinone (HQ), a major metabolite of benzene in humans, significantly inhibited cell viability and colony formation while inducing apoptosis of human bone marrow mononuclear cells in vitro...
September 5, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28882875/class-iii-pi3k-positively-regulates-platelet-activation-and-thrombosis-via-pi-3-p-directed-function-of-nadph-oxidase
#14
Yangyang Liu, Mengjiao Hu, Dongjiao Luo, Ming Yue, Shuai Wang, Xiaoyan Chen, Yangfan Zhou, Yi Wang, Yanchun Cai, Xiaolan Hu, Yuehai Ke, Zhongzhou Yang, Hu Hu
OBJECTIVE: Class III phosphoinositide 3-kinase, also known as vacuolar protein sorting 34 (VPS34), is a highly conserved enzyme regulating important cellular functions such as NADPH oxidase (NOX) assembly, membrane trafficking, and autophagy. Although VPS34 is expressed in platelets, its involvement in platelet activation remains unclear. Herein, we investigated the role of VPS34 in platelet activation and thrombus formation using VPS34 knockout mice. APPROACH AND RESULTS: Platelet-specific VPS34-deficient mice were generated and characterized...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882868/genetic-ablation-of-microrna-33-attenuates-inflammation-and-abdominal-aortic-aneurysm-formation-via-several-anti-inflammatory-pathways
#15
Tetsushi Nakao, Takahiro Horie, Osamu Baba, Masataka Nishiga, Tomohiro Nishino, Masayasu Izuhara, Yasuhide Kuwabara, Hitoo Nishi, Shunsuke Usami, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Naoya Sowa, Satoko Ohno, Hiroki Aoki, Koji Hasagawa, Kazuhisa Sakamoto, Kenji Minatoya, Takeshi Kimura, Koh Ono
OBJECTIVE: Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that microRNA-33 inhibition and genetic ablation of microRNA-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. APPROACH AND RESULTS: MicroRNA-33a-5p expression in central zone of human AAA was higher than marginal zone...
September 7, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28882485/zinc-chloride-rapidly-stimulates-efflux-transporters-in-renal-proximal-tubules-of-killifish-fundulus-heteroclitus
#16
Alexander Zaremba, David S Miller, Gert Fricker
Multidrug resistance-related protein 2 (Mrp2) is an ATP-driven efflux pump at the luminal membrane in renal proximal tubules. It acts as detoxification mechanism by transporting xenobiotics and metabolic products into urine. The trace element zinc is essential for cellular growth, differentiation and survival. It modulates immune response and is used as dietary supplement. Here, we found that 0.1-10μM ZnCl2 rapidly stimulated transport of the Mrp2 probe substrate Texas Red (TR) in isolated killifish renal proximal tubules, which provide an established model system to measure efflux transporter activity by using fluorescent probe substrates, confocal microscopy and image analysis...
November 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28844686/changes-in-white-cell-estimates-and-plasma-chemistry-measurements-following-oral-or-external-dosing-of-double-crested-cormorants-phalacocorax-auritus-with-artificially-weathered-mc252-oil
#17
Karen M Dean, Steven J Bursian, Dave Cacela, Michael W Carney, Fred L Cunningham, Brian Dorr, Katie C Hanson-Dorr, Kate A Healy, Katherine E Horak, Jane E Link, Ian Lipton, Andrew K McFadden, Moira A McKernan, Kendal E Harr
Scoping studies were designed whereby double-crested cormorants (Phalacocorax auritus) were dosed with artificially weathered Deepwater Horizon (DWH) oil either daily through oil injected feeder fish, or by application of oil directly to feathers every three days. Preening results in oil ingestion, and may be an effective means of orally dosing birds with toxicant to improve our understanding of the full range of physiological effects of oral oil ingestion on birds. Blood samples collected every 5-6 days were analyzed for a number of clinical endpoints including white blood cell (WBC) estimates and differential cell counts...
August 25, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28842814/protein-kinase-c-%C3%AE-contributes-to-central-sensitization-in-a-rat-model-of-chronic-migraine
#18
Baixue Wu, Sha Wang, Guangcheng Qin, Jingmei Xie, Ge Tan, Jiying Zhou, Lixue Chen
Protein kinase C γ (PKCγ) is a critical regulator of central sensitization and is widely recognized to be involved in the pathogenesis of chronic migraine (CM). However, the function of PKCγ in CM remains unknown. This study investigated the role of PKCγ on pathogenesis of CM. We repeated infusions of inflammatory soup (IS) on the intact dura of conscious rats to model recurrent trigeminovascular or dural nociceptor activation assumed to occur in patients with CM. The von Frey test was then used to detect changes in pain threshold...
August 25, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28819369/in-vitro-cytotoxic-activities-of-the-oral-platinum-iv-prodrug-oxoplatin-and-hsp90-inhibitor-ganetespib-against-a-panel-of-gastric-cancer-cell-lines
#19
Lukas Klameth, Barbara Rath, Gerhard Hamilton
Gastric cancer exhibits a poor prognosis and is the third most common cause of cancer death worldwide. Chemotherapy of metastatic gastric cancer is based on combinations of platinum drugs and fluoropyrimidines, with added agents. Oxoplatin is a stable oral platinum(IV) prodrug which is converted to a highly active tetrachlorido(IV) complex under acidic conditions. In the present work, we studied the cytotoxic effects of oxoplatin against a panel of four gastric cancer cell lines in vitro. Furthermore, the role of HSP90 in chemoresistance of these lines was investigated using the specific inhibitor ganetespib...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818393/the-modulation-of-the-phosphorylation-status-of-nkcc1-in-organ-cultured-bovine-lenses-implications-for-the-regulation-of-fiber-cell-and-overall-lens-volume
#20
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In this study we have used an antibody that specifically detects the phosphorylation status of the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to study whether the activity of NKCC1 can be regulated in organ cultured bovine lenses. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A...
August 14, 2017: Experimental Eye Research
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