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https://www.readbyqxmd.com/read/29243095/ca2-camkk%C3%AE-pathway-is-required-for-adiponectin-induced-secretion-in-rat-submandibular-gland
#1
Chong Ding, Zhi-Hao Du, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Adiponectin functions as a promoter of saliva secretion in rat submandibular gland via activation of adenosine monophosphate-activated protein kinase (AMPK) and increased paracellular permeability. Ca2+ mobilization is the primary signal for fluid secretion in salivary acinar cells. However, whether intracellular Ca2+ mobilization is involved in adiponectin-induced salivary secretion is unknown. Here, we found that full-length adiponectin (fAd) increased intracellular Ca2+ and saliva secretion in submandibular glands...
December 14, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29242605/ddias-suppresses-trail-mediated-apoptosis-by-inhibiting-disc-formation-and-destabilizing-caspase-8-in-cancer-cells
#2
Joo-Young Im, Bo-Kyung Kim, Ji-Young Lee, Seung-Ho Park, Hyun Seung Ban, Kyeong Eun Jung, Misun Won
DNA damage-induced apoptosis suppressor (DDIAS) has an anti-apoptotic function during DNA damage in lung cancer. However, the anti-apoptotic mechanism of DDIAS in cancer cells under other conditions has not been reported. We report here that DDIAS protects cancer cells from tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by two distinct mechanisms in non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) cells. DDIAS depletion sensitized NSCLC and HCC cells to TRAIL-mediated apoptosis, an effect that was abrogated by pharmacological or genetic inhibition of caspase-8 and was independent of caspase-9, p53, or mitogen-activated protein kinase signaling...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29242118/activation-of-transglutaminase-2-by-nerve-growth-factor-in-differentiating-neuroblastoma-cells-a-role-in-cell-survival-and-neurite-outgrowth
#3
Alanood S Algarni, Alan J Hargreaves, John M Dickenson
NGF (nerve growth factor) and tissue transglutaminase (TG2) play important roles in neurite outgrowth and modulation of neuronal cell survival. In this study, we investigated the regulation of TG2 transamidase activity by NGF in retinoic acid-induced differentiating mouse N2a and human SH-SY5Y neuroblastoma cells. TG2 transamidase activity was determined using an amine incorporation and a peptide cross linking assay. In situ TG2 activity was assessed by visualising the incorporation of biotin-X-cadaverine using confocal microscopy...
December 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29241161/troxerutin-protects-against-myocardial-ischemia-reperfusion-injury-via-pi3k-akt-pathway-in-rats
#4
Liliang Shu, Wanzhe Zhang, Chen Huang, Gongcheng Huang, Gang Su
BACKGROUND/AIMS: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. METHODS: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241041/inhibiting-the-plasmodium-eif2%C3%AE-kinase-pk4-prevents-artemisinin-induced-latency
#5
Min Zhang, Julio Gallego-Delgado, Cristina Fernandez-Arias, Norman C Waters, Ana Rodriguez, Moriya Tsuji, Ronald C Wek, Victor Nussenzweig, William J Sullivan
Artemisinin and its derivatives (ARTs) are frontline antimalarial drugs. However, ART monotherapy is associated with a high frequency of recrudescent infection, resulting in treatment failure. A subset of parasites is thought to undergo ART-induced latency, but the mechanisms remain unknown. Here, we report that ART treatment results in phosphorylation of the parasite eukaryotic initiation factor-2α (eIF2α), leading to repression of general translation and latency induction. Enhanced phosphorylated eIF2α correlates with high rates of recrudescence following ART, and inhibiting eIF2α dephosphorylation renders parasites less sensitive to ART treatment...
December 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29240830/a-low-fat-diet-ameliorates-pathology-but-retains-beneficial-effects-associated-with-cpt1b-knockout-in-skeletal-muscle
#6
Jaycob D Warfel, Bolormaa Vandanmagsar, Shawna E Wicks, Jingying Zhang, Robert C Noland, Randall L Mynatt
Inhibiting fatty acid oxidation is one approach to lowering glucose levels in diabetes. Skeletal muscle specific Carnitine Palmitoyltransferase 1b knockout mice (Cpt1bm-/-) comprise a model of impaired fat oxidation; and have decreased fat mass and enhanced glucose disposal and muscle oxidative capacity compared to controls. However, unfavorable effects occur relative to controls when Cpt1bm-/- mice are fed a 25% fat diet, including decreased activity and fat free mass and increased intramuscular lipid and serum myoglobin...
2017: PloS One
https://www.readbyqxmd.com/read/29240717/a-novel-antibiotic-mechanism-of-l-cyclopropylalanine-blocking-the-biosynthetic-pathway-of-essential-amino-acid-l-leucine
#7
Bingji Ma, Jinwen Shen, Wandee Yindeeyoungyeon, Yuan Ruan
The unusual amino acid l-cyclopropylalanine was isolated from the mushroom Amanita virgineoides after detection in an anti-fungal screening test. l-Cyclopropylalanine was found to exhibit broad-spectrum inhibition against fungi and bacteria. The anti-fungal activity was found to be abolished in the presence of the amino acid l-leucine, but not any other amino acids, indicating that l-cyclopropylalanine may block the biosynthesis of the essential amino acid l-leucine, thereby inhibiting fungal and bacteria growth...
December 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29239334/calycosin-improves-cognitive-function-in-a-transgenic-mouse-model-of-alzheimer-s-disease-by-activating-the-protein-kinase-c-pathway
#8
Lei Song, Xiaoping Li, Xiao-Xue Bai, Jian Gao, Chun-Yan Wang
The major pathological changes in Alzheimer's disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phytoestrogen derived from radix astragali that binds to estrogen receptors to produce estrogen-like effects. Radix astragali Calycosin has been shown to relieve cognitive impairment induced by diabetes mellitus, suggesting calycosin may improve the cognitive function of Alzheimer's disease patients. The protein kinase C pathway is upstream of the mitogen-activated protein kinase pathway and exerts a neuroprotective effect by regulating Alzheimer's disease-related beta amyloid degradation...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29238696/identification-of-clinically-approved-drugs-indacaterol-and-canagliflozin-for-repurposing-to-treat-epidermal-growth-factor-tyrosine-kinase-inhibitor-resistant-lung-cancer
#9
Hongjian Li, Christy Wing-Sum Tong, Yee Leung, Man-Hon Wong, Kenneth Kin-Wah To, Kwong-Sak Leung
In advanced lung cancer, epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) have extraordinary clinical efficacy. However, their usefulness is severely compromised by drug resistance mediated by various mechanisms, the most important of which is the secondary EGFR T790M mutation. The mutation blocks the binding of EGFR TKIs to the receptor kinase, thereby abolishing the therapeutic efficacy. In this study, we used our free and open-source protein-ligand docking software idock to screen worldwide approved small-molecule drugs against EGFR T790M...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29238589/cannabidiol-restores-intestinal-barrier-dysfunction-and-inhibits-the-apoptotic-process-induced-by-clostridium-difficile-toxin-a-in-caco-2-cells
#10
Stefano Gigli, Luisa Seguella, Marcella Pesce, Eugenia Bruzzese, Alessandra D'Alessandro, Rosario Cuomo, Luca Steardo, Giovanni Sarnelli, Giuseppe Esposito
Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity. Objective: The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A...
December 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29238306/calcium-imaging-of-nerve-mast-cell-signaling-in-the-human-intestine
#11
Sabine Buhner, Natasja Barki, Wolfgang Greiter, Pieter Giesbertz, Ihsan E Demir, Güralp O Ceyhan, Florian Zeller, Hannelore Daniel, Michael Schemann
Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations. Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F) in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%). Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29238081/pyridoxine-5-phosphate-oxidase-is-a-novel-therapeutic-target-and-regulated-by-the-tgf-%C3%AE-signalling-pathway-in-epithelial-ovarian-cancer
#12
Lingyun Zhang, Daibing Zhou, Wencai Guan, Weimin Ren, Wenwen Sun, Jimin Shi, Qunbo Lin, Jinguo Zhang, Tiankui Qiao, Yulong Ye, Yun Wu, Yaning Zhang, Xulei Zuo, Kristin L Connor, Guoxiong Xu
Pyridoxine 5'-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5'-phosphate into pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237556/ubiquitination-regulates-the-proteasomal-degradation-and-nuclear-translocation-of-the-fat-mass-and-obesity-associated-fto-protein
#13
Tianyi Zhu, Xuan Ling Hilary Yong, Xia Di, Jocelyn Widagdo, Victor Anggono
Genetic polymorphisms in the fat mass and obesity-associated (FTO) gene have been strongly associated with obesity in humans. The cellular level of FTO is tightly regulated, with alterations in its expression influencing energy metabolism, food intake and body weight. Although the proteasome system is involved, the cellular mechanism underlying FTO protein turnover remains unknown. Here, we report that FTO undergoes post-translational ubiquitination on Lys-216. Knock-in HeLa cells harboring the ubiquitin-deficient K216R mutation displayed a slower rate of FTO turnover, resulting in an increase in the level of FTO as well as enhanced phosphorylation of the ribosomal S6 kinase...
December 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29237505/1-25-dihydroxyvitamin-d3-modulates-the-phenotype-and-function-of-monocyte-derived-dendritic-cells-in-cattle
#14
Yolanda Corripio-Miyar, Richard J Mellanby, Katy Morrison, Tom N McNeilly
BACKGROUND: The active form of the vitamin D3, 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to have major effects not only on physiological processes but also on the regulation of the immune system of vertebrates. Dendritic cells are specialised antigen presenting cells which are in charge of the initiation of T-cell dependant immune responses and as such are key regulators of responses towards pathogens. In this study we set out to evaluate the effects of 1,25-(OH)2D3 on the phenotype of cattle monocyte-derived dendritic cells (MoDCs) and how the conditioning with this vitamin affects the function of these myeloid cells...
December 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29237478/am404-paracetamol-metabolite-prevents-prostaglandin-synthesis-in-activated-microglia-by-inhibiting-cox-activity
#15
Soraya Wilke Saliba, Ariel R Marcotegui, Ellen Fortwängler, Johannes Ditrich, Juan Carlos Perazzo, Eduardo Muñoz, Antônio Carlos Pinheiro de Oliveira, Bernd L Fiebich
BACKGROUND: N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. METHOD: In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA...
December 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29237160/hydrogen-treatment-protects-mice-against-chronic-pancreatitis-by-restoring-regulatory-t-cells-loss
#16
Luguang Chen, Chao Ma, Yun Bian, Jing Li, Tiegong Wang, Li Su, Jianping Lu
BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. METHODS: By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29237157/hypoxia-accelerates-aggressiveness-of-hepatocellular-carcinoma-cells-involving-oxidative-stress-epithelial-mesenchymal-transition-and-non-canonical-hedgehog-signaling
#17
Zhikui Liu, Kangsheng Tu, Yufeng Wang, Bowen Yao, Qing Li, Liang Wang, Changwei Dou, Qingguang Liu, Xin Zheng
BACKGROUND/AIMS: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. METHODS: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation...
December 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29236306/rs4705342-polymorphism-is-involved-in-the-tumorigenesis-of-hbv-positive-hcc-by-altering-the-binding-affinity-of-hbv-induced-nf-kb-with-the-promoter-region-of-microrna-143
#18
Yin Xiuli, Sun Shiying, Zhao Junyan, Yang Jing, Lei Xiaofei, Xu Changqing, Li Kun
BACKGROUND: The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. METHOD: A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western-blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29236055/hyaluronan-production-by-renomedullary-interstitial-cells-influence-of-endothelin-angiotensin-ii-and-vasopressin
#19
Sara Stridh, Fredrik Palm, Tomoko Takahashi, Mayumi Ikegami-Kawai, Malou Friederich-Persson, Peter Hansell
The content of hyaluronan (HA) in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs). Simultaneous treatment with vasopressin and angiotensin II (Ang II) reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2) or hyaluronidases (Hyals), while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%...
December 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29236027/simvastatin-inhibits-cell-proliferation-and-migration-in-human-anaplastic-thyroid-cancer
#20
Mei-Chieh Chen, Yuan-Chin Tsai, Jen-Ho Tseng, Jr-Jiun Liou, Steve Horng, Heng-Ching Wen, Yu-Ching Fan, Wen-Bin Zhong, Sung-Po Hsu
Malignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0-20 μM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation...
December 13, 2017: International Journal of Molecular Sciences
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