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https://www.readbyqxmd.com/read/29342321/contributions-of-material-properties-and-structure-to-increased-bone-fragility-for-a-given-bone-mass-in-the-ucd-t2dm-rat-model-of-type-2-diabetes
#1
Claire Acevedo, Meghan Sylvia, Eric Schaible, James L Graham, Kimber L Stanhope, Lionel N Metz, Bernd Gludovatz, Ann V Schwartz, Robert O Ritchie, Tamara N Alliston, Peter J Havel, Aaron J Fields
Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a given bone mass (micro-CT-derived BMC), and we quantify the roles of T2D-induced deficits in material properties versus bone structure, i.e., geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dl)...
January 17, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29342166/effects-of-vitamin-d-on-insulin-resistance-and-myosteatosis-in-diet-induced-obese-mice
#2
Elisa Benetti, Raffaella Mastrocola, Fausto Chiazza, Debora Nigro, Giuseppe D'Antona, Valentina Bordano, Roberto Fantozzi, Manuela Aragno, Massimo Collino, Marco Alessandro Minetto
Epidemiological studies pointed out to a strong association between vitamin D deficiency and type 2 diabetes prevalence. However, the role of vitamin D supplementation in the skeletal muscle, a tissue that play a crucial role in the maintenance of glucose homeostasis, has been scarcely investigated so far. On this basis, this study aimed to evaluate the effect of vitamin D supplementation in a murine model of diet-induced insulin resistance with particular attention to the effects evoked on the skeletal muscle...
2018: PloS One
https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#3
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#4
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29341863/distinct-gene-signatures-predict-insulin-resistance-in-young-mice-with-high-fat-diet-induced-obesity
#5
Katherine Chen, Alice Jih, Olivia Osborn, Sarah T Kavaler, Wenxian Fu, Roman Sasik, Rintaro Saito, Jane J Kim
Highly inbred C57BL/6 mice show wide variation in their degree of insulin resistance in response to diet-induced obesity even though they are almost genetically identical. Here we employed transcriptional profiling by RNA sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to determine how gene expression patterns correlate with the later development of high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this goal, we partially removed and banked tissues from pubertal mice...
January 8, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29341837/ocular-permeation-of-topical-tazocin-and-its-effectiveness-in-the-treatment-of-pseudomonas-aeruginosa-induced-keratitis-in-rabbits
#6
Sujaya Singh, Renu Agarwal, Zulhilmi Abdul Razak, Robin Ngu, Lwin L Nyein, Sushil Vasudevan, Marina Kapitonova, Azida Juana Kadir, Subrayan Visvaraja
PURPOSE: Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin against systemic Pseudomonas infections, its topical use for the treatment of Pseudomonas keratitis has not been described, hence this study was aimed to find the ocular permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes...
January 17, 2018: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29341779/mesoscopic-transport-in-electrostatically-defined-spin-full-channels-in-quantum-hall-ferromagnets
#7
Aleksandr Kazakov, George Simion, Yuli Lyanda-Geller, Valery Kolkovsky, Zbigniew Adamus, Grzegorz Karczewski, Tomasz Wojtowicz, Leonid P Rokhinson
In this work, we use electrostatic control of quantum Hall ferromagnetic transitions in CdMnTe quantum wells to study electron transport through individual domain walls (DWs) induced at a specific location. These DWs are formed due to the hybridization of two counterpropagating edge states with opposite spin polarization. Conduction through DWs is found to be symmetric under magnetic field direction reversal, consistent with the helical nature of these DWs. We observe that long domain walls are in the insulating regime with a localization length of 4-6  μm...
July 28, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29341046/reduced-growth-hormone-secretion-is-associated-with-nonalcoholic-fatty-liver-disease-in-obese-children
#8
Shuang Liang, Zhen Yu, Xiaobo Song, Yu Wang, Meng Li, Jiang Xue
The purpose of the study was to evaluate the relationship between arginine-levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver disease (NAFLD) in obese children. This study includes a total of 84 obese and 43 normal weight children. The obese subjects are divided into two groups based on the presence or absence of NAFLD. Clinical examination, anthropometric and laboratory examinations, and liver ultrasonography are assessed for all participants. The obese group had significantly lower peak stimulated GH (p<0...
January 16, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29340639/biomechanical-rigidity-and-quantitative-proteomics-analysis-of-segmental-regions-of-the-trabecular-meshwork-at-physiologic-and-elevated-pressures
#9
Janice A Vranka, Julia A Staverosky, Ashok P Reddy, Phillip A Wilmarth, Larry L David, Ted S Acott, Paul Russell, Vijay Krishna Raghunathan
Purpose: The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading cause of irreversible blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus of glaucomatous TM is larger than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions and their response to elevated pressure, are unknown. Methods: We perfused human anterior segments at two pressures using an ex vivo organ culture system...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29340249/a-streptomycin-resistance-marker-in-h-%C3%A2-parasuis-based-on-site-directed-mutations-in-rpsl-gene-to-perform-unmarked-in-frame-mutations-and-to-verify-natural-transformation
#10
Ke Dai, Xintian Wen, Yung-Fu Chang, Sanjie Cao, Qin Zhao, Xiaobo Huang, Rui Wu, Yong Huang, Qigui Yan, Xinfeng Han, Xiaoping Ma, Yiping Wen
Haemophilus parasuis is a member of the family Pasteurellaceae and a major causative agent of Glässer's disease. This bacterium is normally a benign swine commensal but may become a deadly pathogen upon penetration into multiple tissues, contributing to severe lesions in swine. We have established a successive natural transformation-based markerless mutation system in this species. However, the two-step mutation system requires screening of natural competent cells, and cannot delete genes which regulate natural competence per se...
2018: PeerJ
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#11
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340100/the-inhibition-of-cordycepin-on-cancer-stemness-in-tgf-beta-induced-chemo-resistant-ovarian-cancer-cell
#12
Chia-Woei Wang, Bao-Hong Lee, Chen-Jei Tai
Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 μM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340073/ym155-exerts-potent-cytotoxic-activity-against-quiescent-g0-g1-multiple-myeloma-and-bortezomib-resistant-cells-via-inhibition-of-survivin-and-mcl-1
#13
Miyuki Ookura, Tatsuya Fujii, Hideki Yagi, Takuya Ogawa, Shinji Kishi, Naoko Hosono, Hiroko Shigemi, Takahiro Yamauchi, Takanori Ueda, Akira Yoshida
YM155, a novel small molecule inhibitor of survivin, shows broad anticancer activity. Here, we have focused on the cytotoxic activity of YM155 against multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma activity in mouse xenograft model. YM155 suppressed the expression of survivin and rapidly directed Mcl-1 protein for proteasome degradation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#14
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340048/alteration-of-mitochondrial-biogenesis-promotes-disease-progression-in-multiple-myeloma
#15
Xin Zhan, Wenjie Yu, Reinaldo Franqui-Machin, Melissa L Bates, Kalyan Nadiminti, Huojun Cao, Brad A Amendt, Yogesh Jethava, Ivana Frech, Fenghuang Zhan, Guido Tricot
Many cancers, including multiple myeloma (MM), retain more cytosolic iron to promote tumor cell growth and drug resistance. Higher cytosolic iron promotes oxidative damage due to its interaction with reactive oxygen species generated by mitochondria. The variation of mitochondrial biogenesis in different stages of MM disease was evaluated using gene expression profiles in a large clinical dataset. Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial biogenesis signature and oxidative phosphorylation, were increased in myeloma cells compared with normal plasma cells and high expression was associated with an inferior patient outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340044/cepharanthine-hydrochloride-reverses-the-mdr1-p-glycoprotein-mediated-esophageal-squamous-cell-carcinoma-cell-cisplatin-resistance-through-jnk-and-p53-signals
#16
Pengjun Zhou, Rong Zhang, Ying Wang, Dandan Xu, Li Zhang, Jinhong Qin, Guifeng Su, Yue Feng, Hongce Chen, Siyuan You, Wen Rui, Huizhong Liu, Suhong Chen, Hongyuan Chen, Yifei Wang
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is often resistant to therapy. Nowadays, chemotherapy is still one of the main methods for the treatment of ESCC. However, the multidrug resistance (MDR)-mediated chemotherapy resistance is one of the leading causes of death. Exploring agents able to reverse MDR, which thereby increase the sensitivity with clinical first-line chemotherapy drugs, could significantly improve cancer treatment. Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and the mechanism involved have not been reported...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339801/cardiac-glycoside-aglycones-inhibit-hiv-1-gene-expression-by-a-mechanism-requiring-mek1-2-erk1-2-signaling
#17
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339794/hpv-16-virions-can-remain-infectious-for-2-weeks-on-senescent-cells-but-require-cell-cycle-re-activation-to-allow-virus-entry
#18
Justyna Broniarczyk, Nadja Ring, Paola Massimi, Mauro Giacca, Lawrence Banks
Successful infection with Human Papillomaviruses requires mitosis, when incoming viral genomes gain access to nuclear components. However, very little is known about how long HPV particles can remain infectious in non-dividing cells or in which cellular compartments these viruses may reside. To investigate these questions we have used BJ cells as a reversible model of senescence and show that HPV-16 can only infect early-passage proliferating cells. Late-passage senescent cells are resistant to HPV infection, but this can be reversed by inducing cell cycle re-entry with a p53 siRNA...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339763/glucocorticoid-receptor-gr%C3%AE-regulates-glucocorticoid-induced-ocular-hypertension-in-mice
#19
Gaurang C Patel, Yang Liu, J Cameron Millar, Abbot F Clark
Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339541/phd3-controls-lung-cancer-metastasis-and-resistance-to-egfr-inhibitors-through-tgf%C3%AE
#20
Higinio Dopeso, Hui-Ke Jiao, Angel M Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K Garvalov, Till Acker
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance...
January 16, 2018: Cancer Research
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