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https://www.readbyqxmd.com/read/28938696/the-molecular-mechanisms-of-chemoresistance-in-cancers
#1
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938560/inflammatory-factor-tnf-%C3%AE-promotes-the-growth-of-breast-cancer-via-the-positive-feedback-loop-of-tnfr1-nf-%C3%AE%C2%BAb-and-or-p38-p-stat3-hbxip-tnfr1
#2
Xiaoli Cai, Can Cao, Jiong Li, Fuquan Chen, Shuqin Zhang, Bowen Liu, Weiying Zhang, Xiaodong Zhang, Lihong Ye
In the connection between inflammation and cancer development, tumor necrosis factor-alpha (TNF-α) contributes to the tumorigenesis. However, the underlying mechanism remains poorly understood. In this study, we report that TNF-α enhances the growth of breast cancer through up-regulation of oncoprotein hepatitis B X-interacting protein (HBXIP). Our data showed that the levels of TNF-α were positively related to those of HBXIP in clinical breast cancer tissues. Moreover, TNF-α could up-regulate HBXIP in breast cancer cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938454/11%C3%AE-hsd2-sumoylation-modulates-cortisol-induced-mineralocorticoid-receptor-nuclear-translocation-independently-of-effects-on-transactivation
#3
Rubén Jiménez-Canino, Fabián Lorenzo-Díaz, Alex Odermatt, Matthew A Bailey, Dawn E W Livingstone, Frederic Jaisser, Nicolette Farman, Diego Alvarez de la Rosa
The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has an essential role in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor (MR) by converting 11β-hydroxyglucocorticoids to inactive 11-ketosteroids. Congenital deficiency of 11β-HSD2 causes a form of salt-sensitive hypertension known as the syndrome of apparent mineralocorticoid excess. The disease phenotype, which ranges from mild to severe, correlates well with reduction in enzyme activity. Furthermore, polymorphisms in the 11β-HSD2 coding gene (HSD11B2) have been linked to high blood pressure and salt-sensitivity, major cardiovascular risk factors...
September 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28937598/the-effect-of-rankl-opg-balance-on-reducing-implant-complications
#4
REVIEW
Elizabeth R Kapasa, Peter V Giannoudis, Xiaodong Jia, Paul V Hatton, Xuebin B Yang
Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion...
September 22, 2017: Journal of Functional Biomaterials
https://www.readbyqxmd.com/read/28936043/the-potential-of-mangosteen-garcinia-mangostana-peel-extract-combined-with-demineralized-freeze-dried-bovine-bone-xenograft-to-reduce-ridge-resorption-and-alveolar-bone-regeneration-in-preserving-the-tooth-extraction-socket
#5
Utari Kresnoadi, Maretaningtias Dwi Ariani, Eha Djulaeha, Nike Hendrijantini
BACKGROUND: Following the extraction of a tooth, bone resorption can cause significant problems for a subsequent denture implant and restorative dentistry. Thus, the tooth extraction socket needs to be maintained to reduce the chance of any alveolar ridge bone resorption. OBJECTIVE: The objective of this study is to determine whether the administration of mangosteen peel extracts (MPEs), combined with demineralized freeze-dried bovine bone xenograft (DFBBX) materials for tooth extraction socket preservation, could potentially reduce inflammation by decreased the expression of nuclear factor κβ (NfKb) and receptor activator of nuclear factor-κβ ligand (RANKL), to inhibit alveolar bone resorption, and increased of bone morphogenetic protein-2 (BMP2) expressions to accelerate alveolar bone regeneration...
July 2017: Journal of Indian Prosthodontic Society
https://www.readbyqxmd.com/read/28935859/a-non-transcriptional-role-for-the-glucocorticoid-receptor-in-mediating-the-cell-stress-response
#6
Marina Ptushkina, Toryn Poolman, Mudassar Iqbal, Mark Ashe, Janni Petersen, Joanna Woodburn, Magnus Rattray, Anthony Whetton, David Ray
The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal transactivation domain, and the C-terminal ligand binding domain, but not the DNA-binding domain of the GR. This effect was not affected by GR ligand exposure, and occurred without significant GR nuclear accumulation...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935757/resveratrol-inhibits-growth-of-experimental-abdominal-aortic-aneurysm-associated-with-upregulation-of-angiotensin-converting-enzyme-2
#7
Corey S Moran, Erik Biros, Smriti M Krishna, Yutang Wang, Chris Tikellis, Joseph V Moxon, Mark E Cooper, Paul E Norman, Louise M Burrell, Merlin C Thomas, Jonathan Golledge
OBJECTIVE: Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. APPROACH AND RESULTS: Ace2 deletion in apolipoprotein-deficient mice (ApoE(-/)(-)Ace2(-/y) ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers...
September 21, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28935542/phase-i-trial-of-veliparib-a-poly-adp-ribose-polymerase-inhibitor-plus-metronomic-cyclophosphamide-in-metastatic-her2-negative-breast-cancer
#8
Jesus Anampa, Alice Chen, John Wright, Margi Patel, Christine Pellegrino, Karen Fehn, Joseph A Sparano, Eleni Andreopoulou
BACKGROUND: Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. METHODS: The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer...
September 1, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28935156/activation-of-il-17-receptor-leads-to-increased-oxidative-inflammation-in-peripheral-monocytes-of-autistic-children
#9
Ahmed Nadeem, Sheikh F Ahmad, Sabry M Attia, Saleh A Bakheet, Naif O Al-Harbi, Laila Y Al-Ayadhi
Millions of children are affected by different neurodevelopmental disorders, out of which autismspectrum disorder (ASD) poses a major hurdle to normal life style due to associated behavioral abnormalities. Several studies have shown an increased expression/release of Th17 related cytokine, IL-17A in ASD. IL-17A may enhance neuroinflammation via its IL-17A receptor, i.e. IL-17RA expressed in immune cells (such as monocytes) of autistic children. Increased oxidative stress has been implicated in a number of neuropsychiatric disorders including ASD...
September 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28934733/exosomes-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-liver-against-hepatic-ischemia-reperfusion-injury-via-activating-sphingosine-kinase-and-sphingosine-1-phosphate-signaling-pathway
#10
Yingdong Du, Dawei Li, Conghui Han, Haoyu Wu, Longmei Xu, Ming Zhang, Jianjun Zhang, Xiaosong Chen
BACKGROUND/AIMS: This study aimed to evaluate the effects of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury, as well as the underlying mechanisms. METHODS: Exosomes derived from hiPSC-MSCs were isolated and characterized both biochemically and biophysically. hiPSC-MSCs-Exo were injected systemically into a murine ischemia/reperfusion injury model via the inferior vena cava, and then the therapeutic effects were evaluated...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934678/establishment-of-cell-line-with-nk-nkt-phenotype-from-myeloid-nk-cell-acute-leukemia
#11
A Darji, N Desai, R Modi, B Khamar, S Rajkumar
Acute Myeloid Leukemia (AML) is the most common malignancy in adults with a 5-year survival rate of 27% of the total affected population. For effective treatment and new drug discovery, cell lines are considered as a very important tool. Here we report an establishment of a continuous human cell line AML-004 with a hypo-diploid chromosome 44 and presence of both NK/NKT phenotypes. The cell line was isolated from the blood sample of myeloid NK cell acute leukemia patients and extensively characterized by flow cytometery, morphology, and cytogentic analysis...
September 13, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28934090/adipogenic-effects-and-gene-expression-profiling-of-firemaster%C3%A2-550-components-in-human-primary-preadipocytes
#12
Emily W Y Tung, Vian Peshdary, Remi Gagné, Andrea Rowan-Carroll, Carole L Yauk, Adéle Boudreau, Ella Atlas
BACKGROUND: Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated. OBJECTIVES: The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action...
September 14, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28933695/cooperative-interactions-enable-singular-olfactory-receptor-expression-in-mouse-olfactory-neurons
#13
Kevin Monahan, Ira Schieren, Jonah Cheung, Alice Mumbey-Wafula, Edwin S Monuki, Stavros Lomvardas
The monogenic and monoallelic expression of only one out of >1000 mouse olfactory receptor (ORs) genes requires the formation of large heterochromatic chromatin domains that sequester the OR gene clusters. Within these domains, intergenic transcriptional enhancers evade heterochromatic silencing and converge into interchromosomal hubs that assemble over the transcriptionally active OR. The significance of this nuclear organization in OR choice remains elusive. Here, we show that transcription factors Lhx2 and Ebf specify OR enhancers by binding in a functionally cooperative fashion to stereotypically spaced motifs that defy heterochromatin...
September 21, 2017: ELife
https://www.readbyqxmd.com/read/28933478/natural-product-modulators-of-human-sensations-and-mood-molecular-mechanisms-and-therapeutic-potential
#14
REVIEW
Tomáš Pluskal, Jing-Ke Weng
Humans perceive physical information about the surrounding environment through their senses. This physical information is registered by a collection of highly evolved and finely tuned molecular sensory receptors. A multitude of bioactive, structurally diverse ligands have evolved in nature that bind these molecular receptors. The complex, dynamic interactions between the ligands and the receptors lead to changes in our sensory perception or mood. Here, we review our current knowledge of natural products and their derived analogues that interact specifically with human G protein-coupled receptors, ion channels, and nuclear hormone receptors to modulate the sensations of taste, smell, temperature, pain, and itch, as well as mood and its associated behaviour...
September 21, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28933287/modulation-of-abc-transporters-by-nuclear-receptors-physiological-pathological-and-pharmacological-aspects
#15
Juan Pablo Rigalli, Guillermo Nicolás Tocchetti, Johanna Weiss
ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932319/dna-hypomethylation-of-a-transcription-factor-binding-site-within-the-promoter-of-a-gout-risk-gene-nrbp1-upregulates-its-expression-by-inhibition-of-tfap2a-binding
#16
Zaihua Zhu, Weida Meng, Peiru Liu, Xiaoxia Zhu, Yun Liu, Hejian Zou
BACKGROUND: Genome-wide association studies (GWASs) have identified dozens of loci associated with gout, but for most cases, the risk genes and the underlying molecular mechanisms contributing to these associations are unknown. This study sought to understand the molecular mechanism of a common genetic variant, rs780093, in the development of gout, both in vitro and in vivo. RESULTS: Nuclear receptor binding protein 1 (NRBP1), as a gout risk gene, and its regulatory region, 72 bp upstream of the transcription start site, designated as B1, were identified through integrative analyses of genome-wide genotype and DNA methylation data...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28931598/coordinated-increase-of-nuclear-tension-and-lamin-a-with-matrix-stiffness-out-competes-lamin-b-receptor-which-favors-soft-tissue-phenotypes
#17
Amnon Buxboim, Jerome Irianto, Joe Swift, Avathamsa Athirasala, Jae-Won Shin, Florian Rehfeldt, Dennis E Discher
Matrix stiffness that is sensed by a cell or measured by a purely physical probe reflects the intrinsic elasticity of the matrix and also how thick or thin the matrix is. Here, mesenchymal stem cells (MSCs) and their nuclei spread in response to thickness-corrected matrix micro-elasticity, with increases in nuclear tension and nuclear stiffness resulting from increases in myosin-II and lamin-A,C. Linearity between the widely varying projected area of a cell and its nucleus across many matrices, timescales, and myosin-II activity levels indicates a constant ratio of nucleus-to-cell volume, despite the differentiation potential of MSCs...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931192/markers-of-proliferation-and-cytokeratins-in-the-differential-diagnosis-of-jaw-cysts
#18
Nikola D Živković, Dragan S Mihailović, Miloš S Kostić, Ana S Cvetanović, Žaklina Ž Mijović, Maja V Milentijević, Tijana V Denčić
We conducted a retrospective study to analyze the histologic and immunohistochemical findings in three main types of odontogenic cyst. We studied 90 archived cystic jaw lesions: 30 dentigerous cysts, 30 keratocystic odontogenic tumors, and 30 radicular cysts. The cyst types were identified on the basis of clinical, radiologic, and histopathologic findings. Immunohistochemical analyses included staining with Ki-67, p53, epidermal growth factor receptor (EGFR), cytokeratin (CK) 8, CK14, CK17, and CK18. Cell immunopositivity was evaluated for the entire epithelium...
September 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28930982/development-of-a-human-preclinical-model-of-osteoclastogenesis-from-peripheral-blood-monocytes-co-cultured-with-breast-cancer-cell-lines
#19
Laura Mercatali, Chiara Spadazzi, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Alberto Bongiovanni, Federica Recine, Dino Amadori, Toni Ibrahim
The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We developed an in vitro fully human preclinical model of a co-culture of breast cancer cells and monocytes undergoing differentiation towards osteoclasts. We optimized a model of osteoclastogenesis starting from a sample of peripheral blood collected from healthy donors. Peripheral blood mononuclear cells (PBMCs) were first separated by density gradient centrifugation, seeded at a high density and induced to differentiate by adding two growth factors (GFs): receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF)...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930673/pexrap-inhibits-prdm16-mediated-thermogenic-gene-expression
#20
Irfan J Lodhi, John M Dean, Anyuan He, Hongsuk Park, Min Tan, Chu Feng, Haowei Song, Fong-Fu Hsu, Clay F Semenkovich
How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme...
September 19, 2017: Cell Reports
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