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https://www.readbyqxmd.com/read/28423362/trop2-promotes-proliferation-migration-and-metastasis-of-gallbladder-cancer-cells-by-regulating-pi3k-akt-pathway-and-inducing-emt
#1
Xinxing Li, Shifeng Teng, Yanyan Zhang, Weigang Zhang, Xianwen Zhang, Kai Xu, Houshan Yao, Jun Yao, Haolu Wang, Xiaowen Liang, Zhiqian Hu
The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#2
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28395173/particular-phosphorylation-of-pi3k-akt-on-thr308-via-pdk-1-and-pten-mediates-melatonin-s-neuroprotective-activity-after-focal-cerebral-ischemia-in-mice
#3
Ulkan Kilic, Ahmet Burak Caglayan, Mustafa Caglar Beker, Mehmet Yalcin Gunal, Berrak Caglayan, Esra Yalcin, Taha Kelestemur, Reyhan Zeynep Gundogdu, Burak Yulug, Bayram Yılmaz, Bilal Ersen Kerman, Ertugrul Kilic
Apart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI...
April 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28371849/therapeutic-inhibition-of-mir-375-attenuates-post-mi-inflammatory-response-and-left-ventricular-dysfunction-via-pdk-1-akt-signaling-axis
#4
Venkata Naga Srikanth Garikipati, Suresh Kumar Verma, Darukeshwara Jolardarashi, Zhongjian Cheng, Jessica Ibetti, Maria Cimini, Yan Tang, Mohsin Khan, Yujia Yue, Cindy Benedict, Emily Nickoloff, May M Trungcao, Erhe Gao, Prasanna Krishnamurthy, David A Goukassian, Walter J Koch, Raj Kishore
Aims: Increased miR-375 levels has been implicated in rodent models of myocardial infarction (MI) and with patients with heart failure. However, no prior study had established a therapeutic role of miR-375 in ischemic myocardium. Therefore, we assessed whether inhibition of MI-induced miR-375 by LNA anti-miR -375 can improve recovery after acute MI. Methods and Results: Ten weeks old mice were treated with either control or LNA anti miR-375 after induction of MI by LAD ligation...
March 28, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28366735/regulator-of-g-protein-signaling-1-modulates-paraquat-induced-oxidative-stress-and-longevity-via-the-insulin-like-signaling-pathway-in-caenorhabditis-elegans
#5
Mingyu Wu, Xin Kang, Qiang Wang, Chunyu Zhou, Chandra Mohan, Ai Peng
Insulin or insulin like signaling (IIS) pathway is a crucial pathway in Caenorhabditis elegans associated with mediating longevity, and stress resistance. Regulators of G protein signaling (RGS) also modulate stress resistance and longevity in multiple in vitro and in vivo models. However, the mechanism underlying RGS mediating stress resistance and longevity remains largely unclear. Here we report that rgs-1, an important member of rgs family, is a novel modulator of IIS pathway in C. elegans. We found that the loss of rgs-1 dramatically promoted paraquat resistance in C...
May 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28238857/asiaticoside-attenuation-of-rotenone-induced-oxidative-burden-in-a-rat-model-of-hemiparkinsonism-by-maintaining-the-phosphoinositide-mediated-synaptic-integrity
#6
Margabandhu Gopi, Vanisree Arambakkam Janardhanam
Asiaticoside (AS), a triterpenoid saponin isolated from the Indian medicinal herb Centella asiatica is known to exert a neuroprotective effect by attenuating the neurobehavioral, neurochemical and pathological changes in animal models. However, its potential neuroprotection in rotenone-induced hemiparkinsonism which implicates phospholipid-mediated neurotransmission remains unclear. Therefore, we have investigated the neuroprotective effects of AS in rat model of ROT-infused hemiparkinsonism with respect to phosphoinositides-assisted cytodynamics and synaptic function...
February 24, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28163304/predominant-contribution-of-dgk%C3%AE-over-dgk%C3%AE-in-the-control-of-pkc-pdk-1-regulated-functions-in-t-cells
#7
Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, Denise Soutar, Isabel Mérida
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation...
February 28, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#8
Luana Naia, Teresa Cunha-Oliveira, Joana Rodrigues, Tatiana R Rosenstock, Ana Oliveira, Márcio Ribeiro, Catarina Carmo, Sofia I Oliveira-Sousa, Ana I Duarte, Michael R Hayden, A Cristina Rego
Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We previously showed that histone deacetylase inhibitors (HDACi), trichostatin A and sodium butyrate (SB), ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work we investigated the effect of HDACi on regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases (PDK)1/3...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28109078/3-phosphoinositide-dependent-protein-kinase-1-pdk-1-promotes-migration-and-invasion-in-gastric-cancer-cells-through-activating-the-nf-%C3%AE%C2%BAb-pathway
#9
Ning Wu, Changyu He, Bohui Zhu, Jinling Jiang, Yiwen Chen, Tao Ma
Gastric cancer (GC) is one of the most common cancers and the second leading cause of cancer deaths in the world. Manyfactors were reported involving the progression and development of GC. In this study, we aimed to investigate the correlation of 3-phosphoinositide dependent protein kinase 1 (PDK-1) with cell viability, cell migration, and cell invasion of GC. The expression of PDK-1 was measured in different GC cell lines. Thereafter, the expression of PDK-1 was interfered by small hairpin RNA (shRNA) and then incubated with or without the inhibitor of NF-κB pyrrolidine dithiocarbamate (PDTC)...
January 20, 2017: Oncology Research
https://www.readbyqxmd.com/read/28018235/modulation-of-muscle-fiber-compositions-in-response-to-hypoxia-via-pyruvate-dehydrogenase-kinase-1
#10
Daniel D Nguyen, Gyuyoup Kim, Eung-Kwon Pae
Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. Hif-1α and its down-stream molecule Pdk-1 are well known for readily response to hypoxia. We questioned their roles in relation to changes in myosin heavy chain (MyHC) composition in skeletal muscles. We hypothesize that the level of Pdk-1 with respect to the level of Hif-1α determines MyHC composition of the muscle in rats in hypoxia. Young male rats were housed in a chamber maintained at 11...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#11
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
February 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27795296/phd2-is-a-regulator-for-glycolytic-reprogramming-in-macrophages
#12
Annemarie Guentsch, Angelika Beneke, Lija Swain, Katja Farhat, Shunmugam Nagarajan, Ben Wielockx, Kaamini Raithatha, Jan Dudek, Peter Rehling, Anke Zieseniss, Aline Jatho, Mei Chong, Celio X C Santos, Ajay M Shah, Dörthe M Katschinski
The prolyl-4-hydroxylase domain (PHD) enzymes are regarded as the molecular oxygen sensors. There is an interplay between oxygen availability and cellular metabolism, which in turn has significant effects on the functionality of innate immune cells, such as macrophages. However, if and how PHD enzymes affect macrophage metabolism are enigmatic. We hypothesized that macrophage metabolism and function can be controlled via manipulation of PHD2. We characterized the metabolic phenotypes of PHD2-deficient RAW cells and primary PHD2 knockout bone marrow-derived macrophages (BMDM)...
January 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27432037/time-dependent-ppar%C3%AE-modulation-of-hif-1%C3%AE-signaling-in-hypoxic-pulmonary-artery-smooth-muscle-cells
#13
Justine I Blum, Kaiser M Bijli, Tamara C Murphy, Jennifer M Kleinhenz, C Michael Hart
BACKGROUND: Pathogenesis of pulmonary hypertension is complex and involves activation of the transcription factor, hypoxia-inducible factor-1 (HIF-1) that shifts cellular metabolism from aerobic respiration to glycolysis, in part, by increasing the expression of its downstream target pyruvate dehydrogenase kinase-1 (PDK-1), thereby promoting a proliferative, apoptosis-resistant phenotype in pulmonary vascular cells. Activation of the nuclear hormone transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), attenuates pulmonary hypertension and pulmonary artery smooth muscle cell (PASMC) proliferation...
July 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27378235/chlorogenic-acid-extends-the-lifespan-of-caenorhabditis-elegans-via-insulin-igf-1-signaling-pathway
#14
Shan-Qing Zheng, Xiao-Bing Huang, Ti-Kun Xing, Ai-Jun Ding, Gui-Sheng Wu, Huai-Rong Luo
Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague...
April 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/27274101/sirna-induced-silencing-of-hypoxia-inducible-factor-3%C3%AE-hif3%C3%AE-increases-endurance-capacity-in-rats
#15
S Drozdovska, B Gavenauskas, T Drevytska, V Nosar, V Nagibin, I Mankovska, V Dosenko
Molecular mechanisms of adaptation to exercise despite a large number of studies remain unclear. One of the crucial factors in this process is hypoxia inducible factor (HIF) that regulates transcription of many target genes encoding proteins that are implicated in molecular adaptation to hypoxia. Experiments were conducted on 24 adult male Fisher rats. Real-time PCR analysis was performed for quantitative evaluation of Hif3α, Igf1, Glut-4 and Pdk-1 in m. gastrocnemius, m. soleus, in lung and heart tissues...
June 2016: Biology of Sport
https://www.readbyqxmd.com/read/27264671/dynamic-contrast-enhanced-mri-assessing-the-antiangiogenic-effect-of-silencing-hif-1%C3%AE-with-targeted-multifunctional-eco-sirna-nanoparticles
#16
Anthony S Malamas, Erlei Jin, Maneesh Gujrati, Zheng-Rong Lu
Stabilization of hypoxia inducible factor 1α (HIF-1α), a biomarker of hypoxia, in hypoxic tumors mediates a variety of downstream genes promoting tumor angiogenesis and cancer cell survival as well as invasion, and compromising therapeutic outcome. In this study, dynamic contrast enhanced MRI (DCE-MRI) with a biodegradable macromolecular MRI contrast agent was used to noninvasively assess the antiangiogenic effect of RGD-targeted multifunctional lipid ECO/siHIF-1α nanoparticles in a mouse HT29 colon cancer model...
July 5, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/26924725/a-high-fat-diet-induces-sex-specific-differences-in-hepatic-lipid-metabolism-and-nitrite-nitrate-in-rats
#17
Julijana Stanimirovic, Milan Obradovic, Aleksandra Jovanovic, Emina Sudar-Milovanovic, Sonja Zafirovic, Samantha J Pitt, Alan J Stewart, Esma R Isenovic
Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed...
April 1, 2016: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/26845849/-doxorubicin-induced-alterations-in-pro-and-antioxidant-balance-and-their-correction-by-curcumin-in-the-neonatal-rat-cardiomyocytes-culture
#18
O O Linnik, T I Drevytska, O O Gonchar, S A Chornyy, O M Kovalyov, I M Mankovska
It was studied the effect of doxorubicin on the HIF system and the pro-antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1α using doxorubicin at a dose of 0.5 μM was 2.9 ± 0.8 cu, so it decreased by 20% compared to control--3.6 ± 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50...
2015: Fiziolohichnyĭ Zhurnal
https://www.readbyqxmd.com/read/26842781/molecular-characterization-of-the-haemonchus-contortus-phosphoinositide-dependent-protein-kinase-1-gene-hc-pdk-1
#19
Fa-Cai Li, Robin B Gasser, James B Lok, Pasi K Korhonen, Li He, Wen-Da Di, Fang-Yuan Yin, Rui Zhou, Yan-Qin Zhou, Jun-Long Zhao, Min Hu
BACKGROUND: Phosphoinositide-dependent protein kinase-1 (PDK-1), which functions downstream of phosphoinositide 3-kinase (AGE-1) and activates protein kinases of the AGC family, plays critical roles in regulating biology processes, such as metabolism, growth, development and survival. In the free-living nematode Caenorhabditis elegans, PDK-1 is a key component of the insulin-like signalling pathway, regulating the entry into and exit from dauer (arrested development). Although it is proposed that similar molecular mechanisms control the transition from the free-living to the parasitic stages of nematodes, nothing is known about PDK-1 in Haemonchus contortus, a socioeconomically important gastric nematode of ruminants...
February 3, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/26715102/hypoglycemic-activities-of-lyophilized-powder-of-gynura-divaricata-by-improving-antioxidant-potential-and-insulin-signaling-in-type-2-diabetic-mice
#20
Bing-Qing Xu, Ping Yang, Yu-Qing Zhang
BACKGROUND: Diabetes mellitus is a serious disease affecting about 5% of people worldwide. Although several studies have indicated hypoglycemic activities of Gynura divaricata (GD), the mechanisms by which GD improves the symptoms of diabetes remain unclear. OBJECTIVE: The aim of this study was to investigate the potential hypoglycemic effects of GD. DESIGN: The leaves and stems of GD were prepared and lyophilized into a powder, which was added to the diet of mice with type 2 diabetes induced by a high-fat diet in combination with streptozotocin for 4 weeks...
2015: Food & Nutrition Research
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