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https://www.readbyqxmd.com/read/28810742/determination-of-rate-limiting-factor-for-formation-of-beta-catenin-destruction-complexes-using-absolute-protein-quantification
#1
Masashi Kitazawa, Tomohisa Hatta, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Tohru Natsume
Wnt/β-catenin signaling plays important roles in both ontogenesis and development. In the absence of a Wnt stimulus, β-catenin is degraded by a multiprotein "destruction complex" that includes Axin, APC, GSK3B, and FBXW11. Although the key molecules required for transducing Wnt signals have been identified, a quantitative understanding of this pathway has been lacking. Here, we calculated the absolute number of β-catenin destruction complexes by absolute protein quantification using LC-MS/MS. Similar amounts of destruction complex-constituting proteins and β-catenin interacted, and the number of destruction complexes was calculated to be about 1,468 molecules/cell...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#2
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28807209/induction-of-autophagy-reduces-ischemia-reperfusion-injury-in-steatotic-rat-livers
#3
Chunyi Kan, Anding Liu, Haoshu Fang, Olaf Dirsch, Uta Dahmen, Michael Boettcher
BACKGROUND: Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#4
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28699129/shikonin-changes-the-lipopolysaccharide-induced-expression-of-inflammation-related-genes-in-macrophages
#5
Lucia Satiko Yoshida, Tomohito Kakegawa, Yasukatsu Yuda, Hiromi Takano-Ohmuro
We aimed to find candidate molecules possibly involved in the anti-inflammatory activity of shikonin (active compound of "Shikon") by analyzing its effects on gene expression of lipopolysaccharide (LPS)-treated THP-1 macrophages. Polysome-associated mRNAs (those expected to be under translation: translatome) from cells treated with LPS alone (LPS: 5 µg/mL), shikonin alone (S: 100 nM), or LPS plus shikonin (LPS&S) for 3 h were analyzed by DNA microarray followed by detection of enriched pathways/gene ontologies using the tools of the STRING database...
July 11, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28679150/microarray-based-bioinformatics-analysis-of-the-combined-effects-of-sinps-and-pbac-on-cardiovascular-system-in-zebrafish
#6
Hejing Hu, Yannan Zhang, Yanfeng Shi, Lin Feng, Junchao Duan, Zhiwei Sun
With rapid development of nanotechnology and growing environmental pollution, the combined toxic effects of SiNPs and pollutants of heavy metals like lead have received global attentions. The aim of this study was to explore the cardiovascular effects of the co-exposure of SiNPs and lead acetate (PbAc) in zebrafish using microarray and bioinformatics analysis. Although there was no other obvious cardiovascular malformation except bleeding phenotype, bradycardia, angiogenesis inhibition and declined cardiac output in zebrafish co-exposed of SiNPs and PbAc at NOAEL level, significant changes were observed in mRNA and microRNA (miRNA) expression patterns...
October 2017: Chemosphere
https://www.readbyqxmd.com/read/28662458/corrigendum-to-the-gsk3b-gene-confers-risk-for-both-major-depressive-disorder-and-schizophrenia-in-the-han-chinese-population-j-affect-disord-185-2015-149-155
#7
J Chen, M Wang, R A W Khan, K He, Q Wang, Z Li, J Shen, Z Song, W Li, Z Wen, Y Jiang, Y Xu, Y Shi, W Ji
No abstract text is available yet for this article.
October 15, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#8
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28587194/cross-kingdom-regulation-of-putative-mirnas-derived-from-happy-tree-in-cancer-pathway-a-systems-biology-approach
#9
Dinesh Kumar, Swapnil Kumar, Garima Ayachit, Shivarudrappa B Bhairappanavar, Afzal Ansari, Priyanka Sharma, Subhash Soni, Jayashankar Das
MicroRNAs (miRNAs) are well-known key regulators of gene expression primarily at the post-transcriptional level. Plant-derived miRNAs may pass through the gastrointestinal tract, entering into the body fluid and regulate the expression of endogenous mRNAs. Camptotheca acuminata, a highly important medicinal plant known for its anti-cancer potential was selected to investigate cross-kingdom regulatory mechanism and involvement of miRNAs derived from this plant in cancer-associated pathways through in silico systems biology approach...
June 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28578881/increased-myogenic-and-protein-turnover-signaling-in-skeletal-muscle-of-chronic-obstructive-pulmonary-disease-patients-with-sarcopenia
#10
Anita E M Kneppers, Ramon C J Langen, Harry R Gosker, Lex B Verdijk, Nanca Cebron Lipovec, Pieter A Leermakers, Marco C J M Kelders, Chiel C de Theije, Daniel Omersa, Mitja Lainscak, Annemie M W J Schols
BACKGROUND: Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. OBJECTIVE: We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia...
May 31, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/28558704/genome-wide-network-based-pathway-analysis-of-csf-t-tau-a%C3%AE-1-42-ratio-in-the-adni-cohort
#11
Wang Cong, Xianglian Meng, Jin Li, Qiushi Zhang, Feng Chen, Wenjie Liu, Ying Wang, Sipu Cheng, Xiaohui Yao, Jingwen Yan, Sungeun Kim, Andrew J Saykin, Hong Liang, Li Shen
BACKGROUND: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ1-42 are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks...
May 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28509880/analysis-of-different-approaches-for-the-selection-of-reference-genes-in-rt-qpcr-experiments-a-case-study-in-skeletal-muscle-of-growing-mice
#12
Verónica G Piazza, Andrzej Bartke, Johanna G Miquet, Ana I Sotelo
The reliability of reverse transcription-quantitative PCR (RT-qPCR) results in gene expression studies depends on the approaches used to account for non-biological variations. In order to find a proper normalization strategy for the study of genes related to growth hormone signaling in skeletal muscle of growing mice, nine unrelated genes were evaluated as internal controls. According to the most used algorithms-geNorm, the Comparative ΔCq method, NormFinder and BestKeeper-GSK3B, YWHAZ, RPL13A and RN18S were found as the most stable...
May 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28484241/glial-cell-line-derived-neurotrophic-factor-protects-human-islets-from-nutrient-deprivation-and-endoplasmic-reticulum-stress-induced-apoptosis
#13
Shadab Abadpour, Sven O Göpel, Simen W Schive, Olle Korsgren, Aksel Foss, Hanne Scholz
One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483784/thyroid-states-regulate-subcellular-glucose-phosphorylation-activity-in-male-mice
#14
Flavia Letícia Martins Peçanha, Reinaldo Sousa Dos Santos, Wagner Seixas da-Silva
The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK) is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0...
July 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28483667/effect-of-brain-derived-neurotrophic-factor-bdnf-on-hepatocyte-metabolism
#15
Yoni Genzer, Nava Chapnik, Oren Froy
Brain-derived neurotrophic factor (BDNF) plays crucial roles in the development, maintenance, plasticity and homeostasis of the central and peripheral nervous systems. Perturbing BDNF signaling in mouse brain results in hyperphagia, obesity, hyperinsulinemia and hyperglycemia. Currently, little is known whether BDNF affects liver tissue directly. Our aim was to determine the metabolic signaling pathways activated after BDNF treatment in hepatocytes. Unlike its effect in the brain, BDNF did not lead to activation of the liver AKT pathway...
July 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28451058/specific-phospholipid-scramblases-are-involved-in-exposure-of-phosphatidylserine-an-eat-me-signal-for-phagocytes-on-degenerating-axons
#16
Shuji Wakatsuki, Toshiyuki Araki
Axonal degeneration is a key pathological feature of several neurological disorders. Emerging evidence has suggested a pathological connection between axonal degeneration and autophagy, a lysosomal degradation pathway. We recently reported that GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote axonal degeneration. GSK3B-MCL1 pathway affects ATP production locally in degenerating axons and the exposure of phosphatidylserine (PS), an "eat-me" signal for phagocytes, on degenerating axons, resulting in the failed engulfment of axonal debris in vivo...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28427240/ube2t-knockdown-inhibits-gastric-cancer-progression
#17
Changjiang Luo, Yunyi Yao, Zeyuan Yu, Huinian Zhou, Lingyun Guo, Junqiang Zhang, Hongtai Cao, Genyuan Zhang, Yumin Li, Zuoyi Jiao
Ubiquitin-conjugating enzymes (E2 enzymes) such as UBE2T target proteins for degradation via the proteasome. Here, we examined the effects of UBE2T on the progression of gastric cancer. UBE2T was highly expressed in gastric tumors and gastric cancer cells. siRNA-mediated suppression of UBE2T inhibited gastric cancer cell proliferation and colony formation by promoting cell cycle arrest at G2/M phase and increasing apoptosis. Suppression of UBE2T also attenuated the invasive and metastatic abilities of gastric cancer cells by altering expression of epithelial-mesenchymal transition (EMT)-related factors...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427047/co-activation-of-tgf%C3%AE-and-wnt-signalling-pathways-abrogates-emt-in-ovarian-cancer-cells
#18
Tulika Mitra, Sib Sankar Roy
BACKGROUND/AIMS: The aggressive property of ovarian cancer (OC) in terms of epithelial-mesenchymal transition (EMT), proliferation and metastasis are of major concern. Different growth factors including TGFβ are associated with regulating these molecular events but the underlying mechanisms remain unclear. The aim of this report is to decipher the regulation of EMT by co-activation of TGFβ and Wnt signalling cascades in gaining malignancy. METHODS: The expression of the different components of signalling events were analyzed by QPCR, Western blot, Immunofluorescence microscopy and flow cytometry...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28381600/increased-neutrophil-gelatinase-associated-lipocalin-ngal-promotes-airway-remodelling-in-chronic-obstructive-pulmonary-disease
#19
Yujie Wang, Man Jia, Xiaoyi Yan, Limin Cao, Peter J Barnes, Ian M Adcock, Mao Huang, Xin Yao
Airway remodelling is an important component of chronic obstructive pulmonary disease (COPD). Neutrophil gelatinase-associated lipocalin (NGAL) from neutrophils may drive COPD epithelial-mesenchymal transition (EMT). NGAL expression was quantified in the lungs of COPD patients and bronchoalveolar lavage fluid (BALF) of ozone-treated mice. Reticular basement membrane (RBM) thickness and E-cadherin and α-smooth muscle actin (α-SMA) expression were determined in mice airways. Effects of cigarette smoke extract (CSE) and inflammatory factors on NGAL expression in human neutrophils as well as the effects of NGAL on airway structural cells was assessed...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28296937/effects-of-circadian-clock-genes-and-health-related-behavior-on-metabolic-syndrome-in-a-taiwanese-population-evidence-from-association-and-interaction-analysis
#20
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Shih-Jen Tsai
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population...
2017: PloS One
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