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https://www.readbyqxmd.com/read/29349446/ameliorative-role-of-camel-whey-protein-and-rosuvastatin-on-induced-dyslipidemia-in-mice
#1
Nashwa Ahmed El-Shinnawy, Sahar Sobhy Abd Elhalem, Nawal Zakaria Haggag, Gamal Badr
The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia is a major risk factor for a number of chronic diseases, including diabetes and cardiovascular diseases. This work presents a novel approach to study the activity of camel whey protein (WP) with antioxidant and anti-inflammatory properties as a cheap dietary protein substance extracted from camel milk to produce satiety and help in building muscles. Mice model suffering from dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were administrated with either camel WP and/or rosuvastatin for 4 weeks...
January 19, 2018: Food & Function
https://www.readbyqxmd.com/read/29348476/animal-models-of-obesity-and-diabetes-mellitus
#2
REVIEW
Maximilian Kleinert, Christoffer Clemmensen, Susanna M Hofmann, Mary C Moore, Simone Renner, Stephen C Woods, Peter Huypens, Johannes Beckers, Martin Hrabe de Angelis, Annette Schürmann, Mostafa Bakhti, Martin Klingenspor, Mark Heiman, Alan D Cherrington, Michael Ristow, Heiko Lickert, Eckhard Wolf, Peter J Havel, Timo D Müller, Matthias H Tschöp
More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions...
January 19, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29348454/harnessing-insulin-and-leptin-induced-oxidation-of-ptp1b-for-therapeutic-development
#3
Navasona Krishnan, Christopher A Bonham, Ioana A Rus, Om Kumar Shrestha, Carla M Gauss, Aftabul Haque, Ante Tocilj, Leemor Joshua-Tor, Nicholas K Tonks
The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29346275/a-review-on-recent-advances-in-stabilizing-peptides-proteins-upon-fabrication-in-hydrogels-from-biodegradable-polymers
#4
REVIEW
Faisal Raza, Hajra Zafar, Ying Zhu, Yuan Ren, Aftab -Ullah, Asif Ullah Khan, Xinyi He, Han Han, Md Aquib, Kofi Oti Boakye-Yiadom, Liang Ge
Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner...
January 18, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29344506/micrornas-in-renal-diseases-a-potential-novel-therapeutic-target
#5
Federica Petrillo, Anna Iervolino, Miriam Zacchia, Adelina Simeoni, Cristina Masella, Giovanna Capolongo, Alessandra Perna, Giovambattista Capasso, Francesco Trepiccione
Background: MicroRNAs (miRNAs) are a family of short noncoding RNAs that play important roles in posttranscriptional gene regulation. miRNAs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiological and pathological processes. Summary: In the kidney, miRNAs play a role in the organogenesis and in the pathogenesis of several diseases, including renal carcinoma, diabetic nephropathy, cystogenesis, and glomerulopathies...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29343943/the-oral-bioavailability-excretion-and-cytochrome-p450-inhibition-properties-of-epiberberine-an-in-vivo-and-in-vitro-evaluation
#6
Ning Chen, Xiao-Yan Yang, Chang-E Guo, Xin-Ning Bi, Jian-Hua Chen, Hong-Ying Chen, Hong-Pin Li, Hong-Ying Lin, Yu-Jie Zhang
Epiberberine (EPI) is a novel and potentially effective therapeutic and preventive agent for diabetes and cardiovascular disease. To evaluate its potential value for drug development, a specific, sensitive and robust high-performance liquid chromatography-tandem mass spectrometry assay for the determination of EPI in rat biological samples was established. This assay was used to study the pharmacokinetics, bioavailability and excretion of EPI in rats after oral administration. In addition, a cocktail method was used to compare the inhibition characteristics of EPI on cytochrome P450 (CYP450) isoforms in human liver microsomes (HLMs) and rat liver microsomes (RLMs)...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29343652/painless-thyroiditis-and-fulminant-type-1-diabetes-mellitus-in-a-patient-treated-with-an-immune-checkpoint-inhibitor-nivolumab
#7
Kanako Sakurai, Satsuki Niitsuma, Ryota Sato, Kazuhiro Takahashi, Zenei Arihara
The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29342984/amaranthus-caudatus-stimulates-insulin-secretion-in-goto-kakizaki-rats-a-model-of-diabetes-mellitus-type-2
#8
Silvia Zambrana, Lena C E Lundqvist, Virginia Veliz, Sergiu-Bogdan Catrina, Eduardo Gonzales, Claes-Göran Östenson
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats...
January 15, 2018: Nutrients
https://www.readbyqxmd.com/read/29334584/in-vitro-and-in-vivo-metabolite-identification-of-a-novel-benzimidazole-compound-zln005-by-lc-ms-ms
#9
Wenchao Sun, Khoa Dinh Nguyen, William L Fitch, Samuel D Banister, Hongxiang Tang, Xiaolan Zhang, Lewis Yu, Edgar G Engleman, Jayakumar Rajadas
RATIONALE: A novel benzimidazole compound ZLN005 was previously identified as a transcriptional activator of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in certain metabolic tissues. Upregulation of PGC-1α by ZLN005 has been shown to have beneficial effect in a diabetic mouse model and in a coronary artery disease model in vitro. ZLN005 could also have therapeutic potential in neurodegenerative diseases involving down-regulation of PGC-1α. Given the phenotypic efficacy of ZLN005 in several animal models of human disease, its metabolic profile was investigated to guide the development of novel therapeutics using ZLN005 as the lead compound...
January 15, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29333574/unique-metabolic-activation-of-adipose-tissue-macrophages-in-obesity-promotes-inflammatory-responses
#10
Lily Boutens, Guido J Hooiveld, Sourabh Dhingra, Robert A Cramer, Mihai G Netea, Rinke Stienstra
AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a fundamental determinant of macrophage function. In obesity, proinflammatory macrophages accumulate in adipose tissue and trigger chronic low-grade inflammation, that promotes the development of systemic insulin resistance, yet changes in their intracellular energy metabolism are currently unknown. We therefore set out to study metabolic signatures of adipose tissue macrophages (ATMs) in lean and obese conditions...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29332196/bioelectronic-modulation-of-carotid-sinus-nerve-activity-in-the-rat-a-potential-therapeutic-approach-for-type-2-diabetes
#11
Joana F Sacramento, Daniel J Chew, Bernardete F Melo, Matteo Donegá, Wesley Dopson, Maria P Guarino, Alison Robinson, Jesus Prieto-Lloret, Sonal Patel, Bradley J Holinski, Nishan Ramnarain, Victor Pikov, Kristoffer Famm, Silvia V Conde
AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions to repair lost function and reinstate a healthy balance. Carotid sinus nerve (CSN) denervation has been shown to improve glucose homeostasis in insulin-resistant and glucose-intolerant rats; however, these positive effects from surgery appear to diminish over time and are heavily caveated by the severe adverse effects associated with permanent loss of chemosensory function...
January 14, 2018: Diabetologia
https://www.readbyqxmd.com/read/29331414/inhibition-of-fasn-and-er%C3%AE-signalling-during-hyperglycaemia-induced-matrix-specific-emt-promotes-breast-cancer-cell-invasion-via-a-caveolin-1-dependent-mechanism
#12
H A Zielinska, J M P Holly, A Bahl, C M Perks
Since disturbed metabolic conditions such as obesity and diabetes can be critical determinants of breast cancer progression and therapeutic failure, we aimed to determine the mechanism responsible for their pro-oncogenic effects. Using non-invasive, epithelial-like ERα-positive MCF-7 and T47D human breast cancer cells we found that hyperglycaemia induced epithelial to mesenchymal transition (EMT), a key programme responsible for the development of metastatic disease. This was demonstrated by loss of the epithelial marker E-cadherin together with increases in mesenchymal markers such as vimentin, fibronectin and the transcription factor SLUG, together with an enhancement of cell growth and invasion...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331080/design-synthesis-and-evaluation-of-novel-oxazaborine-inhibitors-of-the-nlrp3-inflammasome
#13
Alex George Baldwin, Victor S Tapia, Tessa Swanton, Claire S White, James A Beswick, David Brough, Sally Freeman
The NLRP3 inflammasome is an important regulator of the sterile inflammatory response and its activation by host-derived sterile molecules leads to the intracellular activation of caspase-1, processing of the pro-inflammatory cytokines interleukin-1β (IL 1β)/IL-18, and pyroptotic cell death. Inappropriate activation of NLRP3 drives a chronic inflammatory response and is implicated in several non-communicable diseases, including gout, atherosclerosis, type II diabetes and Alzheimer's disease. In this study, we report the design, synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3 inflammasome inhibitors...
January 13, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29328507/genetics-of-immune-mediated-inflammatory-diseases
#14
REVIEW
Trixy David, Stephanie Ling, Anne Barton
Immune-mediated inflammatory diseases (IMIDs) are characterised by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged...
January 12, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#15
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29322219/sirt6-mediated-transcriptional-suppression-of-txnip-is-critical-for-pancreatic-beta-cell-function-and-survival-in-mice
#16
Kunhua Qin, Ning Zhang, Zhao Zhang, Michael Nipper, Zhenxin Zhu, Jake Leighton, Kexin Xu, Nicolas Musi, Pei Wang
AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system...
January 10, 2018: Diabetologia
https://www.readbyqxmd.com/read/29318471/aav-mediated-gene-delivery-of-the-calreticulin-anti-angiogenic-domain-inhibits-ocular-neovascularization
#17
Leilei Tu, Jiang-Hui Wang, Veluchamy A Barathi, Selwyn M Prea, Zheng He, Jia Hui Lee, James Bender, Anna E King, Grant J Logan, Ian E Alexander, Youn-Shen Bee, Ming-Hong Tai, Gregory J Dusting, Bang V Bui, Jingxiang Zhong, Guei-Sheung Liu
Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization...
January 9, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29315280/gremlin-regulates-podocyte-apoptosis-via-transforming-growth-factor-%C3%AE-tgf-%C3%AE-pathway-in-diabetic-nephropathy
#18
Xiao-Bing Wang, Hong Zhu, Wei Song, Jian-Hua Su
BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting...
January 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29313726/development-and-characterization-of-a-novel-congenic-rat-strain-for-obesity-and-cancer-research
#19
Ann Marie O'Neill, Erin A Gillaspie, Christine M Burrington, Darin T Lynch, Robert T Dauchy, David E Blask, Paul C Tirrell, Brian A Reis, Melissa J Horsman, Michael W Greene
The association between a Western Diet and colon cancer suggests that dietary factors and/or obesity may contribute to cancer progression. Our objective was to develop a new animal model of obesity and the associated pathophysiology to investigate human cancer independent of dietary components that induce obesity. A novel congenic rat strain was established by introducing the fa allele from the Zucker rat into the Rowett Nude rat to generate a "fatty nude rat". The obese phenotype was first characterized in the new model...
January 9, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29312591/metformin-sensitizes-lung-cancer-cells-to-treatment-by-the-tyrosine-kinase-inhibitor-erlotinib
#20
Xiaofei Wang, Keqiang Chen, Ying Yu, Yi Xiang, Jae Hong Kim, Wanghua Gong, Jiaqiang Huang, Guochao Shi, Qingyun Li, Min Zhou, Thomas Sayers, Poonam Tewary, Beili Gao, Ji Ming Wang
Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors such as erlotinib (Erlo), has shown therapeutic benefit, only 15 % patients with mutated epidermal growth factor receptor (EGFR) in lung cancer cells are sensitive. Therefore, additional therapeutic strategy should be developed. In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation...
December 12, 2017: Oncotarget
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