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https://www.readbyqxmd.com/read/29150934/the-current-status-and-perspectives-regarding-the-clinical-implication-of-intracellular-calcium-in-breast-cancer
#1
REVIEW
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca(2+) ) act as second messengers in intracellular signaling. Ca(2+) pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca(2+) as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca(2+) also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150932/high-fat-diet-induced-oxidative-stress-blocks-hepatocyte-nuclear-factor-4%C3%AE-and-leads-to-hepatic-steatosis-in-mice
#2
Dongsheng Yu, Gang Chen, Minglin Pan, Jia Zhang, Wenping He, Yang Liu, Xue Nian, Liang Sheng, Bin Xu
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease with manifestation of over-accumulation of fat in liver. Increasing evidences indicate that NAFLD may be in part caused by malfunction of very low density lipoprotein (VLDL) secretion. Hepatocyte nuclear factor 4α (HNF4α), a nuclear receptor protein, plays an important role in sustain hepatic lipid homeostasis via transcriptional regulation of genes involved in secretion of VLDL, such as apolipoprotein B (ApoB). However, the exact functional change of HNF4α in NAFLD remains to be elucidated...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150901/expression-of-the-clock-gene-rev-erb%C3%AE-in-the-brain-controls-the-circadian-organization-of-food-intake-and-locomotor-activity-but-not-daily-variations-of-energy-metabolism
#3
Satish Sen, Stéphanie Dumont, Dominique Sage-Ciocca, Sophie Reibel, Paul de Goede, Andries Kalsbeek, Etienne Challet
The nuclear receptor REV-ERBα is part of the molecular clock mechanism and thought to be involved in a variety of biological processes within metabolically active peripheral tissues as well. To investigate whether Rev-erbα (also known as Nr1d1) in the brain plays a role in the daily variations of energy metabolism, feeding behaviour and the sleep-wake cycle, we studied mice with global (GKO) or brain (BKO) deletion of Rev-erbα. Mice were studied both in a light-dark cycle and constant darkness, and 24-h variations of Respiratory quotient (RQ) and energy expenditure, as well as the temporal patterns of rest-activity and feeding behavior were recorded...
November 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29150630/inhibition-of-myeloid-differentiation-primary-response-protein-88-provides-neuroprotection-in-early-brain-injury-following-experimental-subarachnoid-hemorrhage
#4
Huiying Yan, Dingding Zhang, Yongxiang Wei, Hongbin Ni, Weibang Liang, Huasheng Zhang, Shuangying Hao, Wei Jin, Kuanyu Li, Chun-Hua Hang
Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150432/the-ikk-related-kinase-tbk1-activates-mtorc1-directly-in-response-to-growth-factors-and-innate-immune-agonists
#5
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Bilgen Ekim Ustunel, Kate A Siroky, Aaron Seth Tooley, Ian E Gonzalez, Daniel H Foley, Hugo A Acosta-Jaquez, Tammy M Barnes, Gabrielle K Steinl, Kae-Won Cho, Carey N Lumeng, Steven M Riddle, Martin G Myers, Diane C Fingar
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29149986/effects-of-cyclosporine-tacrolimus-and-rapamycin-on-osteoblasts
#6
M Martín-Fernández, M Rubert, M Montero, C de la Piedra
PURPOSE: One factor that can contribute to severe bone loss after transplantation is the direct action of immunosuppressants on bone cells. The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on the release of three local factors directly implicated in bone-remodeling regulation and apoptosis of human osteoblasts: interleukin (IL)-6, osteoprotegerin, and receptor activator of nuclear factor κβ (RANKL). BASIC PROCEDURES: Human osteoblasts were obtained from five different patients who underwent orthopedic surgery...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29149648/dried-plum-alleviates-symptoms-of-inflammatory-arthritis-in-tnf-transgenic-mice
#7
Faryal Mirza, Joseph Lorenzo, Hicham Drissi, Francis Y Lee, Do Y Soung
Dried plum (DP), a rich source of polyphenols has been shown to have bone-preserving properties in both animal models of osteoporosis and postmenopausal women. We evaluated if DP alleviated the destruction of joints in transgenic mice (TG) that overexpress human tumor necrosis factor (TNF), a genetic model of rheumatoid arthritis (RA). A four-week treatment of 20% DP diet in TG slowed the onset of arthritis and reduced bone erosions in the joints compared to TG on a regular diet. This was associated with fewer tartrate-resistant acid phosphatase (TRAP) positive cells, suggesting decreased osteoclastogenesis...
October 16, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29149604/nrf1-is-an-er-membrane-sensor-that-is-central-to-cholesterol-homeostasis
#8
Scott B Widenmaier, Nicole A Snyder, Truc B Nguyen, Alessandro Arduini, Grace Y Lee, Ana Paula Arruda, Jani Saksi, Alexander Bartelt, Gökhan S Hotamisligil
Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29149494/inhibiting-mt2-tfe3-dependent-autophagy-enhances-melatonin-induced-apoptosis-in-tongue-squamous-cell-carcinoma
#9
Tengfei Fan, Huifeng Pi, Min Li, Zhenhu Ren, Zhijing He, Feiya Zhu, Li Tian, Manyu Tu, Jia Xie, Mengyu Liu, Yuming Li, Miduo Tan, Gaoming Li, Weijia Qing, Russel J Reiter, Zhengping Yu, Hanjiang Wu, Zhou Zhou
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anti-carcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29149346/novel-pathways-of-endocrine-disruption-through-pesticides-interference-with-human-mineralocorticoid-receptors
#10
Jianyun Zhang, Xin Huang, Hongling Liu, Weiping Liu, Jing Liu
Mineralocorticoid receptor (MR) is one member of the steroid receptor family. In addition to its important role in Na+/K+ homeostasis, MR is reported as a tumor-suppressor in carcinogenesis. So far, little was known about the ability of pesticides to interfere with MR. In this study, a total of 43 pesticides and/or metabolites were investigated for their potential effects on human MR. None of the tested pesticides exhibited MR agonistic potency, while 16 compounds showed antagonistic activities. Further investigations indicated that these 16 chemicals individually antagonized aldosterone-induced alkaline phosphatase expression in vascular smooth muscle cells and aldosterone-inhibited hepatocellular carcinoma cell proliferation at higher concentrations, and the mixture of these 16 pesticides at environmentally relevant concentrations significantly disrupted MR activity...
November 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29148806/discovery-of-tropifexor-ljn452-a-highly-potent-non-bile-acid-fxr-agonist-for-the-treatment-of-cholestatic-liver-diseases-and-nonalcoholic-steatohepatitis-nash
#11
David C Tully, Paul V Rucker, Donatella Chianelli, Jennifer Williams, Agnes Vidal, Phil B Alper, Daniel Mutnick, Badry Bursulaya, James Schmeits, Xiangdong Wu, Dingjiu Bao, Jocelyn Zoll, Young Kim, Todd Groessl, Peter McNamara, H Martin Seidel, Valentina Molteni, Bo Liu, Andrew Phimister, Sean B Joseph, Bryan Laffitte
The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and non-alcoholic steatohepatitis. We identified a novel series of highly potent non-bile acid FXR agonists that introduce a bicyclic nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted isoxazole scaffold...
November 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29148590/effects-of-bergenin-on-methylglyoxal-induced-damage-in-osteoblastic-mc3t3-e1-cells
#12
Kyung Hee Lee, Eun Mi Choi
Bergenin is the main chemical constituent of plants in the genus Bergenia, which are used in traditional medicines. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is the major precursor for forming advanced glycation end products (AGEs). Pretreating MC3T3-E1 cells with bergenin prevented MG-induced protein adduct formation. Bergenin inhibited the MG-induced soluble receptor for AGE (sRAGE), interleukin, reactive oxygen species and mitochondrial superoxide production. Additionally bergenin increased glyoxalase I activity, glutathione, heme oxygenase-1 and nuclear factor erythroid 2-related factor 2 levels in the presence of MG...
November 17, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29148537/adenomatoid-tumors-of-the-male-and-female-genital-tract-are-defined-by-traf7-mutations-that-drive-aberrant-nf-kb-pathway-activation
#13
Benjamin Goode, Nancy M Joseph, Meredith Stevers, Jessica Van Ziffle, Courtney Onodera, Eric Talevich, James P Grenert, Iwei Yeh, Boris C Bastian, Joanna J Phillips, Karuna Garg, Joseph T Rabban, Charles Zaloudek, David A Solomon
Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs)...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29148169/antitumor-and-anti-metastatic-mechanisms-of-rhizoma-paridis-saponins-in-lewis-mice
#14
Shuli Man, Hongyan Chai, Jingxia Cui, Jingwen Yao, Long Ma, Wenyuan Gao
Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion...
November 17, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#15
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#16
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29147012/piperidylmethyloxychalcone-improves-immune-mediated-acute-liver-failure-via-inhibiting-tak1-activity
#17
Sun Hong Park, Jeong-Ah Kwak, Sang-Hun Jung, Byeongwoo Ahn, Won-Jea Cho, Cheong-Yong Yun, Chang Seon Na, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29146687/exercise-induces-muscle-fiber-type-switching-via-transient-receptor-potential-melastatin-2-trpm2-dependent-ca-2-signaling
#18
Seo-Ho Lee, Byung-Ju Kim, Dae-Ryoung Park, Uh-Hyun Kim
The aim of the present study was to examine whether transient receptor potential melastatin 2 (TRPM2) plays a role in muscle fiber type transition during exercise. Mice were trained at a speed of 12 m/min at a slope of 0 ° for 60 min 5 consecutive d/wk for 4-wk. Exhaustion tests were performed on the treadmill (the speed was set at 6 m/min at a slope of 0° and increased at a rate of 1 m/min every 6 min). Isolated primary skeletal muscle cells from TRPM2 knockout (KO) mice showed lower amplitudes of electrical stimuli (ES)-induced Ca(2+) signals when compared to wild-type (WT) mice, due to a defect in Ca(2+) influx...
November 16, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29146573/prostanoid-ep4-agonist-l-902-688-activates-ppar%C3%AE-and-attenuates-pulmonary-arterial-hypertension
#19
Hsin-Hsien Li, Hsao-Hsun Hsu, Gwo-Jyh Chang, I-Chen Chen, Wan-Jing Ho, Pei-Chen Hsu, Wei-Jan Chen, Jong-Hwei Su Pang, Chung-Chi Huang, Ying-Ju Lai
Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cyclic adenosine monophosphate (cAMP) synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH) but this signaling may occur through nuclear peroxisome proliferator-activated receptor-gamma (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activate signal transduction...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29146555/extranuclear-signaling-by-sex-steroid-receptors-and-clinical-implications-in-breast-cancer
#20
REVIEW
Viroj Boonyaratanakornkit, Nalo Hamilton, Diana C Márquez-Garbán, Prangwan Pateetin, Eileen M McGowan, Richard J Pietra
Estrogen and progesterone, play essential roles in the development and progression of breast cancer. Over 70% of breast cancers express estrogen receptors (ER) and progesterone receptors (PR), emphasizing the need for better understanding of ER and PR signaling. ER and PR are traditionally viewed as transcription factors and directly bind DNA to regulate gene networks. In addition to nuclear signaling, ER and PR mediate hormone-induced, rapid extranuclear signaling at the cell membrane or in the cytoplasm which initiates downstream signaling to regulate either rapid or extended cellular responses...
November 13, 2017: Molecular and Cellular Endocrinology
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