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https://www.readbyqxmd.com/read/29155303/therapeutic-vaccine-against-il-1%C3%AE-improved-glucose-control-in-a-mouse-model-of-type-2-diabetes
#1
Yue Zhang, Xiao-Lin Yu, Jun Zha, Li-Zhen Mao, Jia-Qian Chai, Rui-Tian Liu
AIMS: Inflammation is strongly associated with the mechanisms of β-cell failure in type 2 diabetes. Blockade of the key proinflammatory cytokine IL-1β has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1β-targeted therapeutic vaccine consisting of an IL-1β epitope peptide (A1β) and assessed its efficacy on a diabetic KK-A(y) mouse model. MAIN METHODS: KK-A(y) mice were immunized with A1β for three injections at a 2-week interval...
November 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/29152592/revisiting-the-igf-1r-as-a-breast-cancer-target
#2
Roudy Chiminch Ekyalongo, Douglas Yee
The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation...
2017: NPJ Precis Oncol
https://www.readbyqxmd.com/read/29151123/a-coxsackievirus-b-vaccine-protects-against-virus-induced-diabetes-in-an-experimental-mouse-model-of-type-1-diabetes
#3
Virginia M Stone, Minna M Hankaniemi, Emma Svedin, Amirbabak Sioofy-Khojine, Sami Oikarinen, Heikki Hyöty, Olli H Laitinen, Vesa P Hytönen, Malin Flodström-Tullberg
AIMS/HYPOTHESIS: Epidemiological studies suggest a role for Coxsackievirus B (CVB) serotypes in the pathogenesis of type 1 diabetes, but their actual contribution remains elusive. In the present study, we have produced a CVB1 vaccine to test whether vaccination against CVBs can prevent virus-induced diabetes in an experimental model. METHODS: NOD and SOCS1-tg mice were vaccinated three times with either a formalin-fixed non-adjuvanted CVB1 vaccine or a buffer control...
November 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/29142506/detection-of-circulating-natural-antibodies-to-inflammatory-cytokines-in-type-2-diabetes-and-clinical-significance
#4
Weiyi Cai, Cailing Qiu, Hongyu Zhang, Xiangyun Chen, Xuan Zhang, Qingyong Meng, Jun Wei
Background: Inflammatory cytokines have been demonstrated to be involved in developing insulin resistance and type-2 diabetes (T2D). Natural antibodies in the circulation have protective effects on common diseases in humans. The present study was thus designed to test the hypothesis that natural antibodies against inflammatory cytokines could be associated with T2D. Methods: An enzyme-linked immunosorbent assay (ELISA) was developed in-house to detect plasma IgG against peptide antigens derived from interleukin 1α (IL1α), IL1β, IL6, IL8 and tumor necrosis factor-α (TNF-α) in 200 patients with T2D and 220 control subjects...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29141105/the-feasibility-of-intraperitoneal-placenta-derived-mesenchymal-stem-cell-injection-in-stomachs-of-diabetic-mice
#5
Jong Min Park, Sang Hwan Lee, Kwang Il Kim, Won Hee Kim, Joo Young Cho, Ki Baik Hahm, Sung Pyo Hong
BACKGROUND/AIMS: Diabetic gastropathy is associated with loss of Interstitial cells of Cajal (ICCs) and autonomic neuropathy. Effective management for diabetic gastropathy is still unavailable. This study was aimed to confirm the pathogenetic changes in diabetic gastropathy and to examine the effect of treatment with placental derived mesenchymal stem cells (PDMSCs) in stomachs of animal models. METHODS: Fourteen NOD/ShiLtJ mice of 8 weeks were bled until week 30...
November 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29137261/enhanced-response-of-melanoma-cells-to-mek-inhibitors-following-unbiased-igf-1r-down-regulation
#6
Naida Suleymanova, Caitrin Crudden, Claire Worrall, Anica Dricu, Ada Girnita, Leonard Girnita
Due to its ability to compensate for signals lost following therapeutic MAPK-inhibition, insulin-like growth factor type 1 receptor (IGF-1R) co-targeting is a rational approach for melanoma treatment. However IGF-1R conformational changes associated with its inhibition can preferentially activate MAPK-pathway in a kinase-independent manner, through a process known as biased signaling. We explored the impact of biased IGF-1R signaling, on response to MAPK inhibition in a panel of skin melanoma cell lines with differing MAPK and p53 mutation statuses...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135508/new-histologic-finding-of-amyloid-insulin-bodies-at-an-insulin-injection-site-in-a-patient-with-diabetes
#7
Benjamin D Katzman, Peter Traum, Paul B Medline
Amyloidosis is a heterogeneous group of protein deposition diseases with more than 40 known clinical presentations. Localized amyloidosis occurs when the protein deposits exist in a singular location. Patients with diabetes mellitus who inject insulin at the same site can develop localized insulin-derived amyloidosis (AIns) at the injection site, which can be confused clinically with lipoma, lipohyperplasia, lipoatrophy, and fat necrosis. Histologic examination is performed to confirm localized AIns. We report a case of a patient with a long history of type 2 diabetes who presented with a subcutaneous mass in the abdomen at a preferred insulin injection site...
November 7, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29133420/resident-macrophages-of-pancreatic-islets-have-a-seminal-role-in-the-initiation-of-autoimmune-diabetes-of-nod-mice
#8
Javier A Carrero, Derrick P McCarthy, Stephen T Ferris, Xiaoxiao Wan, Hao Hu, Bernd H Zinselmeyer, Anthony N Vomund, Emil R Unanue
Treatment of C57BL/6 or NOD mice with a monoclonal antibody to the CSF-1 receptor resulted in depletion of the resident macrophages of pancreatic islets of Langerhans that lasted for several weeks. Depletion of macrophages in C57BL/6 mice did not affect multiple parameters of islet function, including glucose response, insulin content, and transcriptional profile. In NOD mice depleted of islet-resident macrophages starting at 3 wk of age, several changes occurred: (i) the early entrance of CD4 T cells and dendritic cells into pancreatic islets was reduced, (ii) presentation of insulin epitopes by dispersed islet cells to T cells was impaired, and (iii) the development of autoimmune diabetes was significantly reduced...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29123263/nuclear-igf-1r-predicts-chemotherapy-and-targeted-therapy-resistance-in-metastatic-colorectal-cancer
#9
Jordi Codony-Servat, Miriam Cuatrecasas, Elena Asensio, Carla Montironi, Anna Martínez-Cardús, Mercedes Marín-Aguilera, Carlos Horndler, Eva Martínez-Balibrea, Michele Rubini, Pedro Jares, Oscar Reig, Iván Victoria, Lydia Gaba, Marta Martín-Richard, Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Jaime Feliu, Jose Carlos Méndez, Miguel Méndez, Javier Gallego, Antonieta Salud, Federico Rojo, Antoni Castells, Aleix Prat, Rafael Rosell, Xabier García-Albéniz, Jordi Camps, Joan Maurel
BACKGROUND: Although chemotherapy is the cornerstone treatment for patients with metastatic colorectal cancer (mCRC), acquired chemoresistance is common and constitutes the main reason for treatment failure. Monoclonal antibodies against insulin-like growth factor-1 receptor (IGF-1R) have been tested in pre-treated mCRC patients, but results have been largely deceiving. METHODS: We analysed time to progression, overall survival, and the mutational status of RAS, BRAF and nuclear p-IGF-1R expression by immunohistochemistry, in 470 metastatic CRC patients...
November 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#10
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#11
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29117614/the-effect-of-hypolipidemic-agents-on-thyroid-autoimmunity-in-women-with-hashimoto-s-thyroiditis-treated-with-levothyroxine-and-selenomethionine
#12
Robert Krysiak, Witold Szkróbka, Bogusław Okopień
Background Levothyroxine and selenomethionine were found to reduce thyroid antibody titers in patients with Hashimoto's thyroiditis. The same effect was produced by intensive statin therapy. The aim of the present study was to assess whether hypolipidemic agents modulate the impact of thyroid hormone supplementation and selenomethionine on thyroid autoimmunity. Methods The study included 62 women with Hashimoto's thyroiditis treated for at least 6 months with levothyroxine and selenomethionine. On the basis of plasma lipids, women were divided into three groups: women with isolated hypercholesterolemia (group A; n=20), women with isolated hypertriglyceridemia (group B; n=17), and women with normal plasma lipids (group C; n=25)...
November 8, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/29115357/measuring-biotherapeutic-viscosity-and-degradation-on-chip-with-particle-diffusometry
#13
K N Clayton, D Lee, S T Wereley, T L Kinzer-Ursem
In the absence of efficient ways to test drug stability and efficacy, pharmaceuticals that have been stored outside of set temperature conditions are destroyed, often at great cost. This is especially problematic for biotherapeutics, which are highly sensitive to temperature fluctuations. Current platforms for assessing the stability of protein-based biotherapeutics in high throughput and in low volumes are unavailable outside of research and development laboratories and are not efficient for use in production, quality control, distribution, or clinical settings...
November 21, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29113980/management-of-endocrine-disease-novel-anabolic-treatments-for-osteoporosis
#14
Ernesto Canalis
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...
November 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29107292/fgf21-mimetic-antibody-stimulates-ucp1-independent-brown-fat-thermogenesis-via-fgfr1-%C3%AE-klotho-complex-in-non-adipocytes
#15
Mark Z Chen, Joshua C Chang, Jose Zavala-Solorio, Lance Kates, Minh Thai, Annie Ogasawara, Xiaobo Bai, Sean Flanagan, Victor Nunez, Khanhky Phamluong, James Ziai, Robert Newman, Søren Warming, Ganesh Kolumam, Junichiro Sonoda
OBJECTIVE: Fibroblast Growth Factor 21 (FGF21) is a potent stimulator of brown fat thermogenesis that improves insulin sensitivity, ameliorates hepatosteatosis, and induces weight loss by engaging the receptor complex comprised of Fibroblast Growth Factor Receptor 1 (FGFR1) and the requisite coreceptor βKlotho. Previously, recombinant antibody proteins that activate the FGFR1/βKlotho complex were proposed to act as an FGF21-mimetic; however, in vivo action of these engineered proteins has not been well studied...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29101605/cholesterol-homeostasis-and-cell-proliferation-by-mitogenic-homologs-insulin-benzo-%C3%AE-pyrene-and-uv-radiation
#16
Hemlata Pandey, Ayantika Talukdar, Jeremy S Gangte, S Datta Gupta, N C Chandra
Low-Density Lipoprotein (LDL) is known to promote the unregulated proliferation of cells that is progression of cancer. We aimed to investigate the effect of mitogens on the expression of cell cycle proteins, nuclear cholesterol and cell proliferation. We observed that insulin and benzo-α-pyrene (BaP) induced the expression of Low-Density Lipoprotein receptor (LDLR) on HepG2 cells, thereby enhancing the uptake of LDL. The internalized LDL increased the concentration of cholesterol in the cytoplasm and nucleus of the cell...
November 3, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29093351/effects-of-ursodeoxycholic-acid-and-insulin-on-palmitate-induced-ros-production-and-down-regulation-of-pi3k-akt-signaling-activity
#17
Kunihiro Yokoyama, Yasuaki Tatsumi, Kazuhiko Hayashi, Hidemi Goto, Tetsuya Ishikawa, Shinya Wakusawa
In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29083134/clinical-endocrinology-and-hormones-quantitation-the-increasing-role-of-mass-spectrometry
#18
Federica D'Aurizio, Marco Cantù
Clinical endocrinology has always had a close relationship with laboratory medicine. In fact, the quantification of hormones is of great importance for diagnosis, treatment, recurrence and patient's prognosis of endocrine disorders. This review dealt with the role of the laboratory in diagnosing endocrine pathologies related to adrenal gland, pituitary, gonads and thyroid. The measurements of the main hormones (17- hydroxyprogesterone, androstenedione, dehydroepiandrosterone sulphate, testosterone, estradiol, cortisol, aldosterone, metanephrines, thyroglobulin and insulin-like-growth factor-1) were described considering analytical characteristics but also some aspects of pre-analytical and post- analytical steps...
October 27, 2017: Minerva Endocrinologica
https://www.readbyqxmd.com/read/29079714/tocilizumab-for-the-treatment-of-slc29a3-mutation-positive-phid-syndrome
#19
Nadia K Rafiq, Khalid Hussain, Paul A Brogan
Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) is associated with recessive mutations in SLC29A3, encoding the equilibrative nucleoside transporter hENT3 expressed in mitochondria, causing PHID and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy-plus syndrome. Autoinflammation is increasingly recognized in these syndromes. We previously reported a 16-year-old girl with PHID syndrome associated with severe autoinflammation that was recalcitrant to interleukin-1 and tumor necrosis factor-α blockade...
November 2017: Pediatrics
https://www.readbyqxmd.com/read/29070797/active-immunization-against-hiapp-oligomers-ameliorates-the-diabetes-associated-phenotype-in-a-transgenic-mice-model
#20
Yaron Bram, Sivan Peled, Sayanti Brahmachari, Michael Harlev, Ehud Gazit
Type 2 diabetes is characterized by insulin tolerance in target cells followed by a reduction of pancreatic β-cell mass. Islet amyloid polypeptide oligomeric assemblies were shown to contribute to β-cell apoptosis by forming discrete pores that destabilize the cellular membrane. We previously characterized α-helical cytotoxic islet amyloid polypeptide oligomers which interact with cell membranes, following a complete internalization that leads to cellular apoptosis. Moreover, antibodies which bind the oligomers and neutralize the cytotoxicity were exclusively identified in the serum of type 2 diabetes patients...
October 25, 2017: Scientific Reports
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