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https://www.readbyqxmd.com/read/28324276/the-cytotoxicity-and-genotoxicity-of-particulate-and-soluble-cobalt-in-human-urothelial-cells
#1
Rachel M Speer, Therry The, Hong Xie, Louis Liou, Rosalyn M Adam, John Pierce Wise
Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder...
March 21, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28324067/gestational-protein-restriction-impairs-glucose-disposal-in-the-gastrocnemius-muscles-of-female-rats
#2
C S Blesson, V Chinnathambi, S Kumar, C Yallampalli
Gestational low protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP exposed female offspring. Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months and gastrocnemius muscles were treated with insulin ex vivo for 30 min...
January 30, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324055/substrate-metabolism-and-insulin-sensitivity-during-fasting-in-obese-human-subjects-impact-of-gh-blockade
#3
Morten Høgild Pedersen, Mads Vandsted Svart, Janne Lebeck, Martin Bidlingmaier, Hans Stødkilde-Jørgensen, Steen Bønløkke Pedersen, Niels Møller, Niels Jessen, Jens O L Jørgensen
Context: Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. GH secretion increases during fasting and GH causes insulin resistance. Objective: To study the metabolic effects of GH blockade during fasting in obese subjects. Subjects and Methods: Nine obese males were studied thrice in a randomized design: 1) After an overnight fast (Control), 2) After 72 h fasting (Fasting) and 3) After 72 h fasting with GH blockade (pegvisomant) (Fasting + GHA)...
January 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#4
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#5
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323978/assisted-reproductive-technologies-predispose-to-insulin-resistance-and-obesity-in-male-mice-challenged-with-a-high-fat-diet
#6
David Cerny, Claudio Sartori, Stefano F Rimoldi, Théo Meister, Rodrigo Soria, Elisa Bouillet, Urs Scherrer, Emrush Rexhaj
ART alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the eNOS gene. In eNOS deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We, therefore, assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high fat diet (HFD) during 8 weeks...
February 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323977/short-term-vs-long-term-effects-of-adipocyte-toll-like-receptor-4-activation-on-insulin-resistance-in-male-mice
#7
Caroline Tao, William L Holland, Qiong A Wang, Mengle Shao, Lin Jia, Kai Sun, Xiaoli Lin, Yi-Chun Kuo, Joshua A Johnson, Ruth Gordillo, Joel K Elmquist, Philipp E Scherer
Chronic exposure to diets high in saturated fat (HFD) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance. A possible mediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocyte-specific deletion of TLR4, the "TADIPO mouse". Consistent with a critical role for inflammation as a positive force for healthy adipose tissue expansion, chronic HFD exposure resulted in exacerbated whole body and muscle insulin resistance in the absence of TLR4 in the adipocyte...
February 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323956/hyperhomocysteinemia-promotes-insulin-resistance-and-adipose-tissue-inflammation-in-pcos-mice-through-modulating-m2-macrophage-polarization-via-estrogen-suppression
#8
Xinyu Qi, Bochun Zhang, Yue Zhao, Rong Li, Hsun-Ming Chang, Yanli Pang, Jie Qiao
It has been shown that serum homocycteine (Hcy) levels are higher in women with polycystic ovary syndrome (PCOS). However, the specific role of hyperhomocycteinemia (HHcy) in the development of PCOS has never been reported. Adipose tissue inflammation is featured by the infiltration of macrophages that plays a critical role in the pathogenesis of glucose and insulin intolerance. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) and/or high methionine diet to induce PCOS and HHcy mice models...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323921/emerging-roles-for-micrornas-in-diabetic-microvascular-disease-novel-targets-for-therapy
#9
Yu Zhang, Xinghui Sun, Basak Icli, Mark W Feinberg
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs, non-coding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury...
February 17, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28323920/perinatal-exposure-to-low-dose-bisphenol-a-bpa-disrupts-the-structural-and-functional-development-of-the-hypothalamic-feeding-circuitry
#10
Harry MacKay, Zachary R Patterson, Alfonso Abizaid
Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor due to observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subject to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a pre-existing phenotype produced by BPA exposure...
February 7, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323883/ubiquitously-expressed-human-beta-defensin-1-hbd1-forms-bacteria-entrapping-nets-in-a-redox-dependent-mode-of-action
#11
Judith Raschig, Daniela Mailänder-Sanchez, Anne Berscheid, Jürgen Berger, Adam A Strömstedt, Lioba F Courth, Nisar P Malek, Heike Brötz-Oesterhelt, Jan Wehkamp
Ever since the discovery of endogenous host defense antimicrobial peptides it has been discussed how these evolutionary conserved molecules avoid to induce resistance and to remain effective. An Human ß-defensin 1 (hBD1) is an ubiquitously expressed endogenous antimicrobial peptide that exhibits qualitatively distinct activities between its oxidized and reduced forms. Here, we explore these antimicrobial mechanisms. Surprisingly, using electron microscopy we detected a so far unknown net-like structure surrounding bacteria, which were treated with the reduced but not the oxidized form of hBD1...
March 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28323861/overexpression-of-c-jun-contributes-to-sorafenib-resistance-in-human-hepatoma-cell-lines
#12
Yuki Haga, Tatsuo Kanda, Masato Nakamura, Shingo Nakamoto, Reina Sasaki, Koji Takahashi, Shuang Wu, Osamu Yokosuka
BACKGROUND: Despite recent advances in treatment strategies, it is still difficult to cure patients with hepatocellular carcinoma (HCC). Sorafenib is the only approved multiple kinase inhibitor for systemic chemotherapy in patients with advanced HCC. The majority of advanced HCC patients are resistant to sorafenib. The mechanisms of sorafenib resistance are still unknown. METHODS: The expression of molecules involved in the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma cell lines was examined in the presence or absence of sorafenib...
2017: PloS One
https://www.readbyqxmd.com/read/28323528/plant-immunity-inducer-development-and-application
#13
Dewen Qiu, Yijie Dong, Yi Zhang, Shupeng Li, Fachao Shi
Plant immunity inducers represent a new and rapidly developing field in plant protection research. In this paper, we discuss recent research on plant immunity inducers and their development and applications in China. Plant immunity inducers include plant immunity-inducing proteins, chitosan oligosaccharides, and microbial inducers. These compounds and microorganisms can trigger defense responses and confer disease resistance in plants. We also describe the mechanisms of plant immunity inducers and how they promote plant health...
March 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28323402/single-particle-observation-of-sv40-vp1-polyanion-induced-assembly-shows-that-substrate-size-and-structure-modulate-capsid-geometry
#14
Chenglei Li, Andrew R Kneller, Stephen C Jacobson, Adam Zlotnick
Simian virus 40 capsid protein (VP1) is a unique system for studying substrate-dependent assembly of a nanoparticle. Here, we investigate a simplest case of this system where twelve VP1 pentamers and a single polyanion, e.g. RNA, form a T=1 particle. To test the roles of polyanion substrate length and structure during assembly, we characterized the assembly products with size exclusion chromatography, transmission electron microscopy, and single-particle resistive-pulse sensing. We found that a 500 nt RNA has the optimal length and structure for assembly of uniform T=1 particles...
March 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28320095/dt-13-a-saponin-monomer-13-of-the-dwarf-lilyturf-tuber-synergized-with-vinorelbine-to-induce-mitotic-arrest-via-activation-of-erk-signaling-pathway-in-nci-h1299-cells
#15
Hongyang Li, Li Sun, Hang Li, Xiaodan Lv, Herve Semukunzi, Ruiming Li, Jun Yu, Shengtao Yuan, Sensen Lin
Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320088/flower-extract-of-allium-atroviolaceum-triggered-apoptosis-activated-caspase-3-and-down-regulated-antiapoptotic-bcl-2-gene-in-hela-cancer-cell-line
#16
Somayeh Khazaei, Vasudevan Ramachandran, Roslida Abdul Hamid, Norhaizan Mohd Esa, Ali Etemad, Sara Moradipoor, Patimah Ismail
Cervical cancer accounts for the second most frequent cancer and also third leading cause of cancer mortality (15%) among women worldwide. The major problems of chemotherapeutic treatment in cervical cancer are non-specific cytotoxicity and drug resistance. Plant-derived products, known as natural therapies, have been used for thousands of years in cancer treatment with a very low number of side effects. Allium atroviolaceum is a species in the genus Allium and Liliaceae family, which could prove to have beneficial effects on cancer treatment, although there is a lack of corresponding attention...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320059/effects-of-treadmill-exercise-on-advanced-osteoarthritis-pain-in-rats
#17
Joshua Allen, Ian Imbert, Joshua Havelin, Terry Henderson, Glenn Stevenson, Lucy Liaw, Tamara King
OBJECTIVE: Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating persistent NSAID-resistant ongoing pain associated with advanced OA is unknown. METHODS: Rats treated with intra-articular monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days post-injection. Tactile sensory thresholds and weight bearing were assessed followed by radiographs at weekly intervals...
March 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28319891/time-and-cell-resolved-dynamics-of-redox-sensitive-nrf2-hif-and-nf-%C3%AE%C2%BAb-activities-in-3d-spheroids-enriched-for-cancer-stem-cells
#18
Anna P Kipp, Stefanie Deubel, Elias S J Arnér, Katarina Johansson
Cancer cells have an altered redox status, with changes in intracellular signaling pathways. The knowledge of how such processes are regulated in 3D spheroids, being well-established tumor models, is limited. To approach this question we stably transfected HCT116 cells with a pTRAF reporter that enabled time- and cell-resolved activity monitoring of three redox-regulated transcription factors Nrf2, HIF and NF-κB in spheroids enriched for cancer stem cells. At the first day of spheroid formation, these transcription factors were activated and thereafter became repressed...
March 10, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319809/abt-737-synergizes-with-cisplatin-bypassing-aberration-of-apoptotic-pathway-in-non-small-cell-lung-cancer
#19
Eun Young Kim, Ji Ye Jung, Arum Kim, Yoon Soo Chang, Se Kyu Kim
A subset of non-small cell lung cancer (NSCLC), which does not have a druggable driver mutation, is treated with platinum-based cytotoxic chemotherapy, but it develops resistance triggered by DNA damage responses. Here, we investigated the effect of activation of STAT3 by cisplatin on anti-apoptotic proteins and the effectiveness of a co-treatment with cisplatin and a BH3 mimetic, ABT-737. We analyzed the relationship between cisplatin and STAT3 pathway and effect of ABT-737, when combined with cisplatin in NSCLC cells and K-ras mutant mouse models...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#20
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
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