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https://www.readbyqxmd.com/read/29352507/nuclear-and-membrane-estrogen-receptor-antagonists-induce-similar-mtorc2-activation-reversible-changes-in-synaptic-protein-expression-and-actin-polymerization-in-the-mouse-hippocampus
#1
Fang-Zhou Xing, Yan-Gang Zhao, Yuan-Yuan Zhang, Li He, Ji-Kai Zhao, Meng-Ying Liu, Yan Liu, Ji-Qiang Zhang
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#2
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352272/nuclear-p53-mediated-repression-of-autophagy-involves-pink1-transcriptional-down-regulation
#3
Thomas Goiran, Eric Duplan, Lila Rouland, Wejdane El Manaa, Inger Lauritzen, Julie Dunys, Han You, Frédéric Checler, Cristine Alves da Costa
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352243/nucleolin-and-erbb2-inhibition-reduces-tumorigenicity-of-erbb2-positive-breast-cancer
#4
Eya Wolfson, Shira Solomon, Eran Schmukler, Yona Goldshmit, Ronit Pinkas-Kramarski
ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential player in the cell's growth and proliferation signaling pathways. Amplification or overexpression of ErbB2 is observed in ∼30% of breast cancer patients, and often drives cellular transformation and cancer development. Recently, we have shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein nucleolin, an interaction which enhances cell transformation in vitro, and increases mortality risk and disease progression rate in human breast cancer patients...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352187/reduction-in-hepatic-secondary-bile-acids-caused-by-short-term-antibiotic-induced-dysbiosis-decreases-mouse-serum-glucose-and-triglyceride-levels
#5
Takuya Kuno, Mio Hirayama-Kurogi, Shingo Ito, Sumio Ohtsuki
Antibiotic-caused changes in intestinal flora (dysbiosis) can have various effects on the host. Secondary bile acids produced by intestinal bacteria are ligands for specific nuclear receptors, which regulate glucose, lipid, and drug metabolism in the liver. The present study aimed to clarify the effect of changes in secondary bile acids caused by antibiotic-induced dysbiosis on the host physiology, especially glucose, lipid, and drug metabolism. After oral administration of non-absorbable antibiotics for 5 days, decreased amounts of secondary bile acid-producing bacteria in faeces and a reduction in secondary bile acid [lithocholic acid (LCA) and deoxycholic acid (DCA)] levels in the liver were observed...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352129/molecular-characterization-of-the-grape-seeds-extract-s-effect-against-chemically-induced-liver-cancer-in-vivo-and-in-vitro-analyses
#6
Alaaeldin Ahmed Hamza, Gehan Hussein Heeba, Hanan Mohamed Elwy, Chandraprabha Murali, Raafat El-Awady, Amr Amin
The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352052/estrogen-receptor-positive-breast-cancer-exploiting-signaling-pathways-implicated-in-endocrine-resistance
#7
REVIEW
Adam M Brufsky, Maura N Dickler
Advancements in molecular profiling and endocrine therapy (ET) have led to more focused clinical attention on precision medicine. These advances have expanded our understanding of breast cancer (BC) pathogenesis and hold promising implications for the future of therapy. The estrogen receptor-α is a predominant endocrine regulatory protein in the breast and in estrogen-induced BC. Successful targeting of proteins and genes within estrogen receptor (ER) nuclear and nonnuclear pathways remains a clinical goal...
January 19, 2018: Oncologist
https://www.readbyqxmd.com/read/29351992/involvement-of-aryl-hydrocarbon-receptor-in-myelination-and-in-human-nerve-sheath-tumorigenesis
#8
Ghjuvan'Ghjacumu Shackleford, Nirmal Kumar Sampathkumar, Mehdi Hichor, Laure Weill, Delphine Meffre, Ludmila Juricek, Ingrid Laurendeau, Aline Chevallier, Nicolas Ortonne, Frédérique Larousserie, Marc Herbin, Ivan Bièche, Xavier Coumoul, Mathieu Beraneck, Etienne-Emile Baulieu, Frédéric Charbonnier, Eric Pasmant, Charbel Massaad
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples...
January 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29351391/the-bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-regulate-colonic-epithelial-wound-healing
#9
Magdalena S Mroz, Natalia K Lajczak, Bridie J Goggins, Simon Keely, Stephen Joseph Keely
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although, bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable, supports was assessed over 48 hrs {plus minus} bile acids...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29350911/a-programmable-dna-origami-platform-for-organizing-intrinsically-disordered-nucleoporins-within-nanopore-confinement
#10
Patrick D Ellis Fisher, Qi Shen, Bernice Akpinar, Luke K Davis, Kenny Kwok Hin Chung, David Baddeley, Andela Saric, Thomas J Melia, Bart W Hoogenboom, Chenxiang Lin, C Patrick Lusk
Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated, but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ~40 nm diameter transport channel contributes to their collective properties and function...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29350750/the-hepatoprotective-effect-of-selenium-enriched-yeast-and-gum-arabic-combination-on-carbon-tetrachloride-induced-chronic-liver-injury-in-rats
#11
Mohammed Hamid, Yassin Abdulrahim, Dandan Liu, Gang Qian, Alamzeb Khan, Kehe Huang
The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl4 -intoxication...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29348847/distinct-roles-of-traf6-and-tak1-in-the-regulation-of-adipocyte-survival-thermogenesis-program-and-high-fat-diet-induced-obesity
#12
Yann S Gallot, Joseph D McMillan, Guangyan Xiong, Kyle R Bohnert, Alex R Straughn, Bradford G Hill, Ashok Kumar
Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348827/molecular-genetic-profiling-and-high-throughput-in-vitro-drug-screening-in-nut-midline-carcinoma-an-aggressive-and-fatal-disease
#13
Anja Stirnweiss, Joyce Oommen, Rishi S Kotecha, Ursula R Kees, Alex H Beesley
NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival typically less than seven months, that can arise in people of any age. Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin-binding partner, typically the bromodomain-containing protein BRD4. However, little is known about other genetic aberrations in this disease. In this study, we used a unique panel of cell lines to describe the molecular-genetic features of NMC. Next-generation sequencing identified a recurring high-impact mutation in the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from mutation-signature and network analyses consistent with a general failure in DNA-repair...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348822/the-localization-of-pre-mrna-splicing-factor-prpf38b-is-a-novel-prognostic-biomarker-that-may-predict-survival-benefit-of-trastuzumab-in-patients-with-breast-cancer-overexpressing-her2
#14
Tarek M A Abdel-Fatah, Robert C Rees, A Graham Pockley, Paul Moseley, Graham R Ball, Stephen Y T Chan, Ian O Ellis, Amanda K Miles
Cancer biomarkers that can define disease status and provide a prognostic insight are essential for the effective management of patients with breast cancer (BC). The prevalence, clinicopathological and prognostic significance of PRPF38B expression in a consecutive series of 1650 patients with primary invasive breast carcinoma were examined using immunohistochemistry. Furthermore, the relationship(s) between clinical outcome and PRPF38B expression was explored in 627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with HER2-overexpressing disease...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348675/stac2-negatively-regulates-osteoclast-formation-by-targeting-the-rank-signaling-complex
#15
Eutteum Jeong, Han Kyoung Choi, Jin Hee Park, Soo Young Lee
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29348414/microrna-146a-5p-attenuates-irradiation-induced-and-lps-induced-hepatic-stellate-cell-activation-and-hepatocyte-apoptosis-through-inhibition-of-tlr4-pathway
#16
Yuhan Chen, Zhifeng Wu, Baoying Yuan, Yinying Dong, Li Zhang, Zhaochong Zeng
Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4 and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2. Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS-induced pro-inflammatory cytokine secretion and cell proliferation, and promoted cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1 receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348256/flavonoids-dairy-foods-and-cardiovascular-and-metabolic-health-a-review-of-emerging-biologic-pathways
#17
REVIEW
Dariush Mozaffarian, Jason H Y Wu
A growing body of nutritional science highlights the complex mechanisms and pleiotropic pathways of cardiometabolic effects of different foods. Among these, some of the most exciting advances are occurring in the area of flavonoids, bioactive phytochemicals found in plant foods; and in the area of dairy, including milk, yogurt, and cheese. Many of the relevant ingredients and mechanistic pathways are now being clarified, shedding new light on both the ingredients and the pathways for how diet influences health and well-being...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29348189/cancer-stem-cell-phenotypes-in-er-breast-cancer-models-are-promoted-by-pelp1-aib1-complexes
#18
Thu H Truong, Hsiangyu Hu, Nuri A Temiz, Kyla Hagen, Brian J Girard, Nicholas J Brady, Kathryn L Schwertfeger, Carol A Lange, Julie H Ostrander
Proline, glutamic acid, and leucine rich protein 1 (PELP1) is overexpressed in approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue. However, altered localization of PELP1 to the cytoplasm is an oncogenic event that promotes breast cancer initiation and progression. Herein, interacting partners unique to cytoplasmic PELP1 and the mechanisms by which these interactions promote oncogenic PELP1 signaling were sought...
January 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29348118/targeted-deletion-of-adipocyte-abca1-atp-binding-cassette-transporter-a1-impairs-diet-induced-obesity
#19
Helen Cuffe, Mingxia Liu, Chia-Chi C Key, Elena Boudyguina, Janet K Sawyer, Allison Weckerle, Alexander Bashore, Susan K Fried, Soonkyu Chung, John S Parks
OBJECTIVE: Adipose tissue cholesterol increases with adipocyte triglyceride content and size during development of obesity. However, how adipocyte cholesterol affects adipocyte function is poorly understood. The aim of this study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP-binding cassette transporter A1), on adipose tissue function during diet-induced obesity. APPROACH AND RESULTS: Adiponectin Cre recombinase transgenic mice were crossed with Abca1flox/flox mice to generate ASKO (adipocyte-specific Abca1 knockout) mice...
January 18, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29348072/structure-based-development-of-an-osteoprotegerin-like-glycopeptide-that-blocks-rankl-rank-interactions-and-reduces-ovariectomy-induced-bone-loss-in-mice
#20
Chao Liu, Xiao Chen, Xin Zhi, Weizong Weng, Quan Li, Xiang Li, Yan Zou, Jiacan Su, Hong-Gang Hu
Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis...
January 10, 2018: European Journal of Medicinal Chemistry
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