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https://www.readbyqxmd.com/read/29760565/genome-wide-association-pathway-analysis-to-identify-candidate-single-nucleotide-polymorphisms-and-molecular-pathways-associated-with-tp53-expression-status-in-hbv-related-hepatocellular-carcinoma
#1
Xiwen Liao, Long Yu, Xiaoguang Liu, Chuangye Han, Tingdong Yu, Wei Qin, Chengkun Yang, Guangzhi Zhu, Hao Su, Tao Peng
Background: The aim of this investigation was to identify candidate single nucleotide polymorphisms (SNPs) and molecular pathways associated with tumor protein p53 (TP53) expression status in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), clarify their potential mechanisms, and generate SNP-to-gene to pathway hypothesis. Materials and methods: Identify candidate Causal SNPs and Pathways (ICSNPathway) was used to perform pathway analysis based on the results of our previous genome-wide association study of TP53 expression status in 387 HBV-related HCC patients...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29725001/ablation-of-beta-subunit-of-protein-kinase-ck2-in-mouse-oocytes-causes-follicle-atresia-and-premature-ovarian-failure
#2
Qiu-Xia Liang, Zhen-Bo Wang, Fei Lin, Chun-Hui Zhang, Hong-Mei Sun, Liang Zhou, Qian Zhou, Heide Schatten, Filhol-Cochet Odile, Boldyreff Brigitte, Qing-Yuan Sun, Wei-Ping Qian
Premature ovarian failure (POF), a major cause of female infertility, is a complex disorder, but the molecular mechanisms underlying the disorder are only poorly understood. Here we report that protein kinase CK2 contributes to maintaining follicular survival through PI3K/AKT pathway and DNA damage response pathway. Targeted deletion of CK2β in mouse oocytes from the primordial follicle stage resulted in female infertility, which was attributed to POF incurring by massive follicle atresia. Downregulated PI3K/AKT signaling was found after CK2β deletion, indicated by reduced level of phosphorylated AKT (S473, T308, and S129) and altered AKT targets related to cell survival...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29704527/tacrine-derivatives-stimulate-human-glioma-sf295-cell-death-and-alter-important-proteins-related-to-disease-development-an-old-drug-for-new-targets
#3
Fernanda Nunes, Letícia Barros Silva, Evelyn Winter, Adny Henrique Silva, Leônidas João de Melo, Michele Rode, Marcos Antônio Pinto Martins, Nilo Zanatta, Sarah Coelho Feitosa, Hélio Gauze Bonacorso, Tânia Beatriz Creczynski-Pasa
Glioblastoma is the most common and aggressive glioma, characterized by brain invasion capability. Being very resistant to the current therapies, since even under treatment, surgery, and chemotherapy with temozolomide (TMZ), patients achieve a median survival of one year. In the search for more effective therapies, new molecules have been designed. For nervous system cancers, molecules able to cross the blood-brain barrier are handled with priority. Accordingly, tacrine was chosen for this study and the inclusion of spiro-heterocyclic rings was done in its structure resulting in new compounds...
April 25, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29700097/prostaglandin-e2-receptor-3-ep3-signaling-is-induced-in-placentas-with-unexplained-recurrent-pregnancy-losses-urpl
#4
Yao Ye, Aurelia Vattai, Nina Ditsch, Christina Kuhn, Martina Rahmeh, Sven Mahner, Myriam Ripphahn, Roland Immler, Markus Sperandio, Udo Jeschke, Viktoria von Schoenfeldt
Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy and it can stimulate inflammatory reactions via EP3. However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether prostaglandin E2 receptor 3 (EP3) signaling is involved in the mechanism of uRPL...
April 26, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29696608/regulation-of-aging-and-oxidative-stress-pathways-in-aged-pancreatic-islets-using-alpha-lipoic-acid
#5
Navid Nobakht-Haghighi, Mahban Rahimifard, Maryam Baeeri, Mohammad Amin Rezvanfar, Shermineh Moini Nodeh, Hamed Haghi-Aminjan, Emre Hamurtekin, Mohammad Abdollahi
Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study investigates the anti-aging, anti-apoptotic, and antioxidant properties of alpha-lipoic acid (ALA), aiming to improve aged rat pancreatic cells. In this regard, half maximal effective concentration (EC50 ) of ALA based on the survival of aged pancreatic islet cells was determined as 100 µM. Following this, p38 and p53 genes expression as key factors in aging, oxidative stress biomarkers, insulin secretion, and Pdx1 protein expression were evaluated using real-time PCR, ELISA reader, and fluorescence microscope...
April 25, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29673160/mechanisms-of-diabetes-induced-endothelial-cell-senescence-role-of-arginase-1
#6
Esraa Shosha, Zhimin Xu, S Priya Narayanan, Tahira Lemtalsi, Abdelrahman Y Fouda, Modesto Rojas, Ji Xing, David Fulton, R William Caldwell, Ruth B Caldwell
We have recently found that diabetes-induced premature senescence of retinal endothelial cells is accompanied by NOX2-NADPH oxidase-induced increases in the ureohydrolase enzyme arginase 1 (A1). Here, we used genetic strategies to determine the specific involvement of A1 in diabetes-induced endothelial cell senescence. We used A1 knockout mice and wild type mice that were rendered diabetic with streptozotocin and retinal endothelial cells (ECs) exposed to high glucose or transduced with adenovirus to overexpress A1 for these experiments...
April 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29625119/the-exosome-of-adipose-derived-stem-cells-reduces-%C3%AE-amyloid-pathology-and-apoptosis-of-neuronal-cells-derived-from-the-transgenic-mouse-model-of-alzheimer-s-disease
#7
Mijung Lee, Jae-Jun Ban, Seungwon Yang, Wooseok Im, Manho Kim
Adipose-derived stem cells (ADSC) have a therapeutic potential for the treatment of neurodegenerative disorders such as Alzheimer's disease (AD). Exosomes are extracellular vesicles secreted from various types of cells, and stem cell-derived exosomes are known to have beneficial effects in many diseases. Many studies have suggested that amyloid beta (Aβ) peptides have a pivotal role in AD progression, by mitochondrial dysfunction of neuronal cells. We examined the therapeutic potential of exosomes derived from ADSCs (ADSC-Exo) in preventing the disease phenotypes induced by the Aβ cascade in an AD in vitro model...
April 3, 2018: Brain Research
https://www.readbyqxmd.com/read/29594354/detection-of-the-merkel-cell-polyomavirus-in-the-neuroendocrine-component-of-combined-merkel-cell-carcinoma
#8
Thibault Kervarrec, Mahtab Samimi, Pauline Gaboriaud, Tarik Gheit, Agnès Beby-Defaux, Roland Houben, David Schrama, Gaëlle Fromont, Massimo Tommasino, Yannick Le Corre, Eva Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Hervé Maillard, Adeline Furudoï, Patrick Michenet, Antoine Touzé, Serge Guyétant
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. The main etiological agent is Merkel cell polyomavirus (MCPyV), detected in 80% of cases. About 5% of cases, called combined MCC, feature an admixture of neuroendocrine and non-neuroendocrine tumor cells. Reports of the presence or absence of MCPyV in combined MCC are conflicting, most favoring the absence, which suggests that combined MCC might have independent etiological factors and pathogenesis. These discrepancies might occur with the use of different virus identification assays, with different sensitivities...
March 28, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29587258/sulodexide-slows-down-the-senescence-of-aortic-endothelial-cells-exposed-to-serum-from-patients-with-peripheral-artery-diseases
#9
Patrycja Sosińska-Zawierucha, Beata Maćkowiak, Ryszard Staniszewski, Katarzyna Sumińska-Jasińska, Magdalena Maj, Zbigniew Krasiński, Andrzej Bręborowicz
BACKGROUND/AIMS: Aging of the arterial endothelial cells results in the appearance of their inflammatory phenotype, which may predispose patients to the acceleration of arteriosclerosis. We studied the effect of serum from patients with peripheral artery disease (PAD) on the senescence of human aortic endothelial cells (HAEC) and how that process is modulated by sulodexide. METHODS: HAEC replicative aging in vitro was studied in the presence of 10% PAD-serum (PAD Group) or10%PAD serum and Sulodexide 0...
March 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29568365/amiodarone-promotes-cancer-cell-death-through-elevated-truncated-srsf3-and-downregulation-of-mir-224
#10
Yung-Lung Chang, Shu-Ting Liu, Yi-Wen Wang, Wei-Shiang Lin, Shih-Ming Huang
Amiodarone is a widely used class III antiarrhythmic agent which prolongs the action potential and refractory period by blockage of several types of myocardial potassium channels. Emerging evidence suggests that amiodarone sensitize tumor cells in response to chemotherapy. Nevertheless, little is known about the underlying molecular mechanism. To gain further insight, we demonstrated that amiodarone accumulated the population of a premature termination codon-containing isoform of serine and arginine rich splicing factor 3 ( SRSF3-PTC ) without increasing alternative spliced p53 beta isoform...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29546074/matrine-ameliorates-colorectal-cancer-in-rats-via-inhibition-of-hmgb1-signaling-and-downregulation-of-il-6-tnf-%C3%AE-and-hmgb1
#11
Huizhen Fan, Chunyan Jiang, Baoyuan Zhong, Jianwen Sheng, Ting Chen, Qingqing Chen, Jingtao Li, Hongchuan Zhao
Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF- α ), transforming growth factor beta 1 (TGF- β 1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29532999/nutlin-3a-as-a-novel-anticancer-agent-for-adrenocortical-carcinoma-with-ctnnb1-mutation
#12
Wen Hui, Shenghua Liu, Jie Zheng, Zujun Fang, Qiang Ding, Chenchen Feng
Adrenocortical carcinoma (ACC) is a rare malignancy, and CTNNB1 is frequently mutated in ACC. Our study aims to screen for effective agents with antineoplastic activity against ACC with CTNNB1 mutation. In-silico screening of the Genomics of Drug Sensitivity in Cancer (GDSC) database was conducted. Drug sensitivity in cells with CTNNB1 mutation was analyzed and further in vitro and in vivo studies were performed using the compound. Only one compound, Nutlin-3a, an MDM2 inhibitor, was significantly sensitive in 18 cancer cells with CTNNB1 mutation...
April 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29446977/establishment-growth-proliferation-and-gene-expression-of-buffalo-bubalus-bubalis-transgenic-fetal-fibroblasts-containing-human-insulin-gene-and-production-of-embryos-by-handmade-cloning-using-these-cells
#13
Parul Mehta, Ramakant Kaushik, Karn Pratap Singh, Ankur Sharma, Manoj Kumar Singh, Manmohan Singh Chauhan, Prabhat Palta, Suresh Kumar Singla, Radhey Sham Manik
The aim of the present study was to compare transgenic cells, containing human insulin gene kept under the control of mammary gland-specific buffalo beta-lactoglobulin promoter, and their counterparts, that is, nontransgenic cells, for examining their potential for the production of embryos following somatic cell nuclear transfer (SCNT). The gene construct was delivered into buffalo fetal fibroblasts (BFF) by nucleofection following which, the transfected cells were selected by culture in the presence of G418 for 3 weeks...
April 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29390191/inducible-knockdown-of-endothelial-protein-tyrosine-phosphatase-1b-promotes-neointima-formation-in-obese-mice-by-enhancing-endothelial-senescence
#14
Marianne Jäger, Astrid Hubert, Rajinikanth Gogiraju, Magdalena L Bochenek, Thomas Münzel, Katrin Schäfer
AIMS: Protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of receptor tyrosine kinase signaling. In this study, we determined the importance of PTP1B expressed in endothelial cells for the vascular response to arterial injury in obesity. RESULTS: Morphometric analysis of vascular lesions generated by 10% ferric chloride (FeCl3 ) revealed that tamoxifen-inducible endothelial PTP1B deletion (Tie2.ERT2 -Cre × PTP1Bfl/fl ; End.PTP1B knockout, KO) significantly increased neointima formation, and reduced numbers of (endothelial lectin-positive) luminal cells in End...
February 1, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#15
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
December 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29163768/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#16
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#17
REVIEW
E T Aristizabal Prada, C J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mammalian target of rapamycin (mTOR) inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However, clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression-free survival due to tumour resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP system are needed...
January 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29110583/beta-mangostin-from-cratoxylum-arborescens-activates-the-intrinsic-apoptosis-pathway-through-reactive-oxygen-species-with-downregulation-of-the-hsp70-gene-in-the-hl60-cells-associated-with-a-g0-g1-cell-cycle-arrest
#18
Fatima Abdelmutaal Ahmed Omer, Najihah Binti Mohd Hashim, Mohamed Yousif Ibrahim, Firouzeh Dehghan, Maizatulakmal Yahayu, Hamed Karimian, Landa Zeenelabdin Ali Salim, Syam Mohan
Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#19
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches necessitates the development of alternative testing approaches. A body of evidence associates DILI with the induction of stress-response genes in liver cells. Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs. To this end, we employed ATTAGENE's cell-based multiplexed reporter assay, the FACTORIAL transcription factor (TF), that enables quantitative assessment of the activity of multiple stress-responsive TFs in a single well of cells...
March 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29063982/role-of-beta-adrenergic-receptors-and-sirtuin-signaling-in-the-heart-during-aging-heart-failure-and-adaptation-to-stress
#20
REVIEW
Regina Celia Spadari, Claudia Cavadas, Ana Elisa T Saturi de Carvalho, Daniela Ortolani, Andre Luiz de Moura, Paula Frizera Vassalo
In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (β-ARs), mainly the beta 1 (β1 -AR) and beta 2 (β2 -AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The β2 -ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the β1 /β2 -AR ratio and activation of the β2 -AR-Gi-PI3K-Akt signaling pathway have been observed...
January 2018: Cellular and Molecular Neurobiology
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