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https://www.readbyqxmd.com/read/28733520/the-ketogenic-diet-is-not-feasible-as-a-therapy-in-a-cd-1-nu-nu-mouse-model-of-renal-cell-carcinoma-with-features-of-stauffer-s-syndrome
#1
Silvia Vidali, Sepideh Aminzadeh-Gohari, René Günther Feichtinger, Renaud Vatrinet, Andreas Koller, Felix Locker, Tricia Rutherford, Maura O'Donnell, Andrea Stöger-Kleiber, Bridget Lambert, Thomas Klaus Felder, Wolfgang Sperl, Barbara Kofler
The ketogenic diet (KD), a high-fat low-carbohydrate diet, has shown some efficacy in the treatment of certain types of tumors such as brain tumors and neuroblastoma. These tumors are characterized by the Warburg effect. Because renal cell carcinoma (RCC) presents similar energetic features as neuroblastoma, KD might also be effective in the treatment of RCC. To test this, we established xenografts with RCC 786-O cells in CD-1 nu/nu mice and then randomized them to a control diet or to KDs with different triglyceride contents...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732748/controlling-the-pro-inflammatory-function-of-6-sulfo-lacnac-slan-dendritic-cells-with-dimethylfumarate
#2
Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BACKROUND: The fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS...
June 24, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28730964/ccl2-is-modulated-by-cytokines-and-ppar-g-in-anaplastic-thyroid-cancer
#3
Silvia Martina Ferrari, Giusy Elia, Simona Piaggi, Enke Baldini, Salvatore Ulisse, Mario Miccoli, Gabriele Materazzi, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. METHODS: We tested in "primary human anaplastic thyroid carcinoma (ATC) cells" (ANA) versus "normal thyroid follicular cells" (TFC): a) CCL2 secretion basally, after IFN-g and/or TNF-a stimulation; b) PPARg activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28728928/gtf-231-a-mixture-of-gymnemic-acid-trigonelline-and-ferulic-acid-significantly-ameliorates-oxidative-stress-in-experimental-type-2-diabetes-in-rats
#4
Roshana Devi Vellai, Sharmila Chandiran, Subramanian Sorimuthu Pillai
OBJECTIVES: According to a report by the United States National Health and Nutrition Examination Survey, nearly 60% of patients with diabetes have more than one complication caused by chronic diabetes. Type 2 diabetes is a multifactorial metabolic disorder that accounts for more than 95% of people with diabetes and usually requires multitargeted therapeutic interventions. It arises due to insufficient insulin secretion or its action or both. Recently, we reported that the oral administration of gymnemic acid, trigonelline and ferulic acid in the ratio of 2:3:1 (GTF-231), a mixture of 3 phytoingredients at a concentration of 300 mg/kg body weight significantly improved the glucose homeostasis in rats with low-dose streptozotocin-induced type 2 diabetes that were fed with high-fat diet...
July 17, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28726640/c1q-tnf-related-protein-6-ctrp6-links-obesity-to-adipose-tissue-inflammation-and-insulin-resistance
#5
Xia Lei, Marcus M Seldin, Hannah C Little, Nicholas Choy, Thomas Klonisch, G William Wong
Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug, rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#6
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28721154/obesity-and-inflammation-the-linking-mechanism-and-the-complications
#7
Mohammed S Ellulu, Ismail Patimah, Huzwah Khaza'ai, Asmah Rahmat, Yehia Abed
Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28717133/insulin-upregulates-betatrophin-expression-via-pi3k-akt-pathway
#8
Puhan Lu, Xi Chen, Zeqing Zhang, Jianhua Zhang, Yan Yang, Zhelong Liu, Junhui Xie, Shiying Shao, Xinrong Zhou, Shuhong Hu, Wentao He, Jiajun Zhao, Xuefeng Yu
Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#9
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL-6, IL-1 and IL-12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors, and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#10
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716041/potentially-inappropriate-home-medications-among-older-patients-with-cardiovascular-disease-admitted-to-a-cardiology-service-in-usa
#11
Marwan Sheikh-Taha, Hani Dimassi
BACKGROUND: The use of potentially inappropriate medications (PIMs) may pose more risks than benefits to patients and is a major factor contributing to the likelihood of serious adverse drug reactions and negative health outcomes among older patients. METHODS: A retrospective chart review was conducted in a tertiary care center in USA where home medications of the older patients were reviewed and analyzed upon hospital admission over three months, from March till May 2016...
July 17, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28710249/amyloid-precursor-protein-in-pancreatic-islets
#12
Joshua Kulas, Kendra Puig, Colin K Combs
The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque forming peptide in Alzheimer's disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well characterized consequence of type 1 and type 2 diabetes. In this study we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes...
July 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28708885/pioglitazone-ameliorates-glomerular-nlrp3-inflammasome-activation-in-apolipoprotein-e-knockout-mice-with-diabetes-mellitus
#13
Yao Wang, Bo Yu, Li Wang, Ming Yang, Zhiyin Xia, Wei Wei, Fengyu Zhang, Xiaochen Yuan
OBJECTIVE: The NLRP3 inflammasome plays an important role in the pathogenesis of inflammation in diabetic nephropathy (DN). Pioglitazone (PIO) has been found to exert an anti-inflammatory effect in patients with diabetes mellitus, but it is still unclear whether PIO exhibits a similar effect in DN. We aimed to explore the effect and underlying mechanism of PIO on DN, as well as investigate if NLRP3 is a pharmacologic target of PIO. METHODS: We divided 48 apolipoprotein E (apoE) (-/-) mice into 4 groups: apoE (-/-), apoE (-/-) with PIO, diabetic apoE (-/-), and diabetic apoE (-/-) with PIO...
2017: PloS One
https://www.readbyqxmd.com/read/28707770/comparison-of-the-paracrine-activity-of-mesenchymal-stem-cells-derived-from-human-umbilical-cord-amniotic-membrane-and-adipose-tissue
#14
Filip A Dabrowski, Anna Burdzinska, Agnieszka Kulesza, Anna Sladowska, Aleksandra Zolocinska, Kamila Gala, Leszek Paczek, Miroslaw Wielgos
AIM: The study was conducted to investigate secretory activity and define the paracrine potential of mesenchymal stem cells from human umbilical cord and amniotic membrane (UC-MSCs and AM-MSCs, respectively). METHODS: UC-MSCs (n = 6) were obtained from tissue explants using an adherent method after two weeks of incubation. AM-MSCs (n = 6) were obtained by digestion with tripsin and collagenase. MSC phenotype was confirmed in vitro by performing flow cytometry, differentiation assays and vimentin staining...
July 14, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28707492/bisphenol-a-bpa-aggravates-multiple-low-dose-streptozotocin-induced-type-1-diabetes-in-c57bl-6-mice
#15
Marina Cetkovic-Cvrlje, Sinduja Thinamany, Kylie A Bruner
Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28705797/cyclical-cushing-s-how-best-to-catch-the-ups-and-downs
#16
Malik Asif Humayun, Tanya Hart, Tristan Richardson
A 68-year-old man with a background of hypertension and type 2 diabetes presented with fluctuating symptoms of muscle aches and pains and tiredness. His initial work-up for the possibility of hypercortisolaemia showed a completely variable pattern, with 24-hour cortisol excretion and serum cortisol post 1 mg dexamethasone suppression test ranging from normal to significantly elevated. A series of salivary cortisol with symptom diary confirmed the cyclical nature of hypercortisolaemia, and his concomitant adrenocorticotropic hormone (ACTH) levels were elevated...
July 13, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28704555/a-system-model-of-the-effects-of-exercise-on-plasma-interleukin-6-dynamics-in-healthy-individuals-role-of-skeletal-muscle-and-adipose-tissue
#17
Micaela Morettini, Maria Concetta Palumbo, Massimo Sacchetti, Filippo Castiglione, Claudia Mazzà
Interleukin-6 (IL-6) has been recently shown to play a central role in glucose homeostasis, since it stimulates the production and secretion of Glucagon-like Peptide-1 (GLP-1) from intestinal L-cells and pancreas, leading to an enhanced insulin response. In resting conditions, IL-6 is mainly produced by the adipose tissue whereas, during exercise, skeletal muscle contractions stimulate a marked IL-6 secretion as well. Available mathematical models describing the effects of exercise on glucose homeostasis, however, do not account for this IL-6 contribution...
2017: PloS One
https://www.readbyqxmd.com/read/28703796/p75-ntr-antagonists-attenuate-photoreceptor-cell-loss-in-murine-models-of-retinitis-pigmentosa
#18
María Platón-Corchado, Pablo F Barcelona, Sean Jmaeff, Miguel Marchena, Alberto M Hernández-Pinto, Catalina Hernández-Sánchez, H Uri Saragovi, Enrique J de la Rosa
ProNGF signaling through p75(NTR) has been associated with neurodegenerative disorders. Retinitis pigmentosa (RP) comprises a group of inherited retinal dystrophies that causes progressive photoreceptor cell degeneration and death, at a rate dependent on the genetic mutation. There are more than 300 mutations causing RP, and this is a challenge to therapy. Our study was designed to explore a common mechanism for p75(NTR) in the progression of RP, and assess its potential value as a therapeutic target. The proNGF/p75(NTR) system is present in the dystrophic retina of the rd10 RP mouse model...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#19
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28701510/immunomodulatory-molecule-irak-m-balances-macrophage-polarization-and-determines-macrophage-responses-during-renal-fibrosis
#20
Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, Georg Lorenz, Roman Günthner, Simone Romoli, Regina Gröbmayr, Heni-Eka Susanti, Jan Potempa, Joanna Koziel, Maciej Lech
Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD)...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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