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https://www.readbyqxmd.com/read/28644842/investigation-of-discriminant-metabolites-in-tamoxifen-resistant-and-choline-kinase-alpha-downregulated-breast-cancer-cells-using-1h-nuclear-magnetic-resonance-spectroscopy
#1
Hoe Suk Kim, Lianji Tian, Hyeonjin Kim, Woo Kyung Moon
Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28644004/the-intricate-effects-of-alpha-amino-and-lysine-modifications-on-arginine-methylation-on-the-n-terminal-tail-of-histone-h4
#2
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood...
June 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28643917/estrogen-receptor-alpha-mediates-mandibular-condylar-cartilage-growth-in-male-mice
#3
J L Robinson, V Gupta, P Soria, E Clanaman, S Gurbarg, M Xu, J Chen, S Wadhwa
OBJECTIVES: In the appendicular skeleton, estrogen via ERα signalling has been shown to mediate endochondral growth plate fusion in both males and females. However, the role of ERα in mediating growth of the mandibular condylar cartilage is unknown. Thus, this study focuses on the characterization of the mandibular condylar cartilage phenotype in young and adult male ERαKO mice. SETTING: Columbia University Medical Center. MATERIAL AND METHODS: WT and ERαKO C57BL/6 male mice were sacrificed at 49 days or 9 months for phenotypic analysis...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643803/vhl-deficiency-augments-anthracycline-sensitivity-of-clear-cell-renal-cell-carcinomas-by-down-regulating-aldh2
#4
Yao-Hui Gao, Zhao-Xia Wu, Li-Qi Xie, Cai-Xia Li, Yu-Qin Mao, Yan-Tao Duan, Bing Han, San-Feng Han, Yun Yu, Hao-Jie Lu, Peng-Yuan Yang, Tian-Rui Xu, Jing-Lin Xia, Guo-Qiang Chen, Li-Shun Wang
The von Hippel-Lindau (VHL) is deficient in ∼70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in ccRCC cells...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642869/detection-of-microrna-in-hepatic-cirrhosis-and-hepatocellular-carcinoma-in-hepatitis-c-genotype-4-in-egyptian-patients
#5
Hala M Demerdash, Hend M Hussien, Ehab Hassouna, Emad A Arida
BACKGROUND: In Egypt, the prevalence of chronic hepatitis C (CHC) infection is 13.8% of whole population and about 80% of the patients with hepatocellular carcinoma have underling hepatitis C. AIM: This study was designed to assess the diagnostic value of plasma miR-122 and miR-21 in patients with CHC, genotype-4, to detect fibrosis progression versus noninvasive indices and their diagnostic value in detection of early stages of hepatocellular carcinoma (HCC). METHODOLOGY: A prospective study that included 180 patients, divided into 3 groups: healthy controls (group I), CHC patients (group II), and hepatitis C patients with HCC (group III); all cases were subjected to thorough clinical, radiological, and laboratory investigations...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642232/a-single-amino-acid-residue-at-transmembrane-domain-4-of-the-alpha-subunit-influences-carisoprodol-direct-gating-efficacy-at-gabaa-receptors
#6
Manoj Kumar, Manish Kumar, John Freund, Glenn H Dillon
The muscle relaxant carisoprodol (CSP, trade name Soma) has recently been controlled at the federal level as a Schedule IV drug due to its high abuse potential and consequences of misuse, such as withdrawal syndrome, delusions, seizures and even death. Recent work has shown that carisoprodol can directly gate and allosterically modulate the GABAA receptor. These actions are subunit-dependent; compared to other GABAA receptors, carisoprodol has nominal direct gating effects in α3β2γ2receptors. Here, using site-directed-mutagenesis and whole cell patch clamp electrophysiology in transiently transfected HEK293 cells, we examined the role of GABAA receptor α subunit transmembrane domain 4 (TM4) amino acids in direct gating and allosteric modulatory actions of carisoprodol...
June 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28642153/characterization-of-the-differential-coregulator-binding-signatures-of-the-retinoic-acid-receptor-subtypes-upon-ant-agonist-action
#7
Ignacio Miro Estruch, Diana Melchers, René Houtman, Laura H J de Haan, John P Groten, Jochem Louisse, Ivonne M C M Rietjens
Retinoic Acid Receptor alpha (RARα/NR1B1), Retinoic Acid Receptor beta (RARβ/NR1B2) and Retinoic Acid Receptor gamma (RARγ/NR1B3) are transcription factors regulating gene expression in response to retinoids. Within the RAR genomic pathways, binding of RARs to coregulators is a key intermediate regulatory phase. However, ligand-dependent interactions between the wide variety of coregulators that may be present in a cell and the different RAR subtypes are largely unknown. The aim of this study is to characterize the coregulator binding profiles of RARs in the presence of the pan-agonist all-trans-Retinoic Acid (AtRA); the subtype-selective agonists Am80 (RARα), CD2314 (RARβ) and BMS961 (RARγ); and the antagonist Ro415253...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#8
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28642128/immunomodulation-of-parkinson-s-disease-using-mucuna-pruriens-mp
#9
REVIEW
Sachchida Nand Rai, Hareram Birla, Walia Zahra, Saumitra Sen Singh, Surya Pratap Singh
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2)...
June 19, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28642056/can-stem-cells-ameliorate-the-pancreatic-damage-induced-by-streptozotocin-in-rats
#10
Amira Ragab El Barky, Amany Abdel Hamid Ezz, Abeer Abd-Elhameed Alm-Eldeen, Samy Ali Hussein, Yehia Ahmed Hafez, Tarek Mostafa Mohamed
BACKGROUND: Stem cell therapy holds great promise for the repair of injured tissues and organs, and it is one of the most promising therapies for diabetes mellitus. Therefore, the present study was undertaken to elucidate the antidiabetic effect of both mesenchymal stem cells (MSCs) and insulin-producing cells (IPCs) on streptozotocin (STZ)-induced diabetes in rats. MATERIALS AND METHODS: MSCs were derived from bone marrow of male albino rats. MSCs were characterized morphologically and by Cluster of differentiation (CD(-ve34)) and (CD(+ve105))...
June 19, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28641926/targeting-the-gm-csf-receptor-for-the-treatment-of-cns-autoimmunity
#11
Igal Ifergan, Todd S Davidson, Hania Kebir, Dan Xu, Daphne Palacios-Macapagal, Jennifer Cann, Jane M Rodgers, Zoe N Hunter, Camille L Pittet, Sara Beddow, Clare A Jones, Alexandre Prat, Matthew A Sleeman, Stephen D Miller
In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes...
June 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28641482/insights-into-eukaryotic-evolution-from-transmembrane-domain-lengths
#12
Aditya Mittal, Snigdha Singh
Biological membranes, comprised of proteins anchored by their trans-membrane domains (TMDs) creating a semi-permeable phase with lipid constituents, serve as "checkposts" for not only intracellular trafficking in eukaryotic cells but also for material transactions of all living cells with external environments. Hydropathy (or hydrophobicity) plots of "bitopic" proteins (i.e. having single alpha-helical TMDs) are routinely utilized in biochemistry texts for predicting their TMDs. The number of amino acids (i...
June 22, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28641010/alpha-mangostin-reverses-multidrug-resistance-by-attenuating-the-function-of-the-multidrug-resistance-linked-abcg2-transporter
#13
Chung-Pu Wu, Sung-Han Hsiao, Megumi Murakami, Yu-Jen Lu, Yan-Qing Li, Yang-Hui Huang, Tai-Ho Hung, Suresh V Ambudkar, Yu-Shan Wu
The ATP-binding cassette (ABC) drug transporter ABCG2 can actively efflux a wide variety of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular accumulation of these drugs. Therefore, the overexpression of ABCG2 often contributes to the development of multidrug resistance (MDR) in cancer cells, which is one of the major obstacles to successful cancer chemotherapy. Moreover, ABCG2 is highly expressed in various tissues including the intestine and blood-brain barrier (BBB), limiting the absorption and bioavailability of many therapeutic agents...
June 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28641003/synthesis-and-anti-inflammatory-evaluation-of-2-aminobenzaldehydes-via-ir-iii-catalyzed-c-h-amidation-of-aldimines-with-acyl-azides
#14
Saegun Kim, Prashant Chakrasali, Hyo Sun Suh, Neeraj Kumar Mishra, Taeyoung Kim, Sang Hoon Han, Hyung Sik Kim, Byung-Moo Lee, Soo Bong Han, In Su Kim
The aldimine-directed C-H amidation of various arenes with N-acyl azides as amidation surrogates under cationic iridium(III) catalysis is described. This transformation efficiently provides a range of 2-aminobenzaldehydes derivatives with excellent site-selectivity and functional group compatibility. The resulting 2-aminobenzaldehyde framework provides facile access to a range of biologically interesting heterocycles. In addition, all synthetic compounds were screened for anti-inflammatory activity against interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) with lipopolysaccharide (LPS)-induced RAW264...
June 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28639948/protective-effects-of-il28ra-sirna-on-cardiomyocytes-in-hypoxia-reoxygenation-injury
#15
Ge Gong, Yanyan Li, Xinxing Yang, Hongyu Geng, Xinzheng Lu, Liansheng Wang, Zhijian Yang
OBJECTIVE: We demonstrate the protective effects of the siRNA-mediated inhibition of the interleukin-28 receptor alpha (IL28RA) subunit on cardiomyocytes in hypoxia/reoxygenation (H/R) injury and explore the associated mechanism. METHODS: After designing and synthesizing three pairs of siRNA that effectively reduced IL28RA gene expression in vitro (siRNA-6158, siRNA-6160, and siRNA-6162), primary neonatal rat cardiomyocytes were transfected using a liposome transfection method...
June 22, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28639900/the-novel-cxcr4-antagonist-prx177561-reduces-tumor-cell-proliferation-and-accelerates-cancer-stem-cell-differentiation-in-glioblastoma-preclinical-models
#16
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Flora Vitale, Antonella Vetuschi, Simona Pompili, Giulia Rossi, Francesco Marampon, Peter J Richardson, Lee Patient, Lee Patient, Stephen Burbidge, Claudio Festuccia
Glioblastoma is the most frequent and the most lethal primary brain tumor among adults. Standard of care is the association of radiotherapy with concomitant or adjuvant temozolomide. However, to date, recurrence is inevitable. The CXCL12/CXCR4 pathway is upregulated in the glioblastoma tumor microenvironment regulating tumor cell proliferation, local invasion, angiogenesis, and the efficacy of radio-chemotherapy. In this study, we evaluated the effects of the novel CXCR4 antagonist, PRX177561, in preclinical models of glioblastoma...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639884/loss-of-tumor-suppressor-mir-126-contributes-to-the-development-of-hepatitis-b-virus-related-hepatocellular-carcinoma-metastasis-through-the-upregulation-of-adam9
#17
Le-Yang Xiang, Huo-Hui Ou, Xin-Cheng Liu, Zhan-Jun Chen, Xiang-Hong Li, Yu Huang, Ding-Hua Yang
Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639693/thromboelastography-may-predict-risk-of-grade-2-bleeding-in-thrombocytopenic-patients
#18
E N Opheim, T O Apelseth, S J Stanworth, G E Eide, T Hervig
BACKGROUND AND OBJECTIVES: Platelet count is used as a prophylactic platelet transfusion trigger, although evidence suggests that it is a poor predictor of bleeding. Thus, alternative tests are required. The primary objective of this study was to compare thromboelastography (TEG) parameters on days with and without bleeding symptoms. The secondary objectives were to investigate the relationship between TEG parameters and haematological variables, fever, C-reactive protein (CRP) and platelet transfusion...
June 22, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28639200/treatment-of-liver-cancer-by-c-ebpa-sarna
#19
Xiaoyang Zhao, Jon Voutila, Stephanos Ghobrial, Nagy A Habib, Vikash Reebye
The prognosis for hepatocellular carcinoma (HCC) remains poor and has not improved in over two decades. Most patients with advanced HCC who are not eligible for surgery have limited treatment options due to poor liver function or large, unresectable tumors. Although sorafenib is the standard-of-care treatment for these patients, only a small number respond. For the remaining, the outlook remains bleak. A better approach to target "undruggable" molecular pathways that reverse HCC is therefore urgently needed...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28638614/loss-of-kae1-expression-in-collecting-ducts-of-end-stage-kidneys-from-a-family-with-slc4a1-g609r-associated-distal-renal-tubular-acidosis
#20
Alfred A Vichot, Zsuzsanna K Zsengellér, Boris E Shmukler, Nancy D Adams, Neera K Dahl, Seth L Alper
Distal renal tubular acidosis caused by missense mutations in kidney isoform of anion exchanger 1 (kAE1/SLC4A1), the basolateral membrane Cl(-)/HCO3(-) exchanger of renal alpha-intercalated cells, has been extensively investigated in heterologous expression systems but rarely in human kidneys. The preferential apical localization of distal renal tubular acidosis (dRTA)-associated kAE1 mutants R901X, G609R and M909T in cultured epithelial monolayers has not been examined in human kidney. Here, we present kidney tissues from dRTA-affected siblings heterozygous for kAE1 G609R, characterized by predominant absence rather than mistargeting of kAE1 in intercalated cells...
February 2017: Clinical Kidney Journal
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