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https://www.readbyqxmd.com/read/28324011/a-novel-fc-fgf21-with-improved-resistance-to-proteolysis-increased-affinity-towards-%C3%AE-klotho-and-enhanced-efficacy-in-mice-and-cynomolgus-monkeys
#1
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M Véniant, Jing Xu
FGF21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C-terminus of FGF21 (A180E) that the new molecule, Fc-FGF21(RGE), has gained many improved attributes...
January 26, 2017: Endocrinology
https://www.readbyqxmd.com/read/28318623/the-complexity-of-chronic-kidney-disease-mineral-and-bone-disorder-across-stages-of-chronic-kidney%C3%A2-disease
#2
Fabiana G Graciolli, Katia R Neves, Fellype Barreto, Daniela V Barreto, Luciene M Dos Reis, Maria E Canziani, Yves Sabbagh, Aluizio B Carvalho, Vanda Jorgetti, Rosilene M Elias, Susan Schiavi, Rosa M A Moysés
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#3
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28299522/glycoconjugates-reveal-diversity-of-human-neural-stem-cells-hnscs-derived-from-human-induced-pluripotent-stem-cells-hipscs
#4
Majury Kandasamy, Lars Roll, Daniel Langenstroth, Oliver Brüstle, Andreas Faissner
Neural stem cells (NSCs) have the ability to self-renew and to differentiate into various cell types of the central nervous system. This potential can be recapitulated by human induced pluripotent stem cells (hiPSCs) in vitro. The differentiation capacity of hiPSCs is characterized by several stages with distinct morphologies and the expression of various marker molecules. We used the monoclonal antibodies (mAbs) 487(LeX), 5750(LeX) and 473HD to analyze the expression pattern of particular carbohydrate motifs as potential markers at six differentiation stages of hiPSCs...
March 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28299499/evaluation-of-vitreous-levels-of-advanced-glycation-end-products-and-angiogenic-factors-as-biomarkers-for-severity-of-diabetic-retinopathy
#5
Makiko Katagiri, Jun Shoji, Noriko Inada, Satoshi Kato, Shigehiko Kitano, Yasuko Uchigata
BACKGROUND/AIMS: Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups...
March 15, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28298517/phosphoproteomics-of-fgf1-signaling-in-chondrocytes-identifying-the-signature-of-inhibitory-response
#6
Jessica R Chapman, Olga Katsara, Rachel Ruoff, David Morgenstern, Shruti Nayak, Claudio Basilico, Beatrix Ueberheide, Victoria Kolupaeva
Fibroblast growth factor (FGF) signaling is vital for many biological processes, beginning with development. The importance of FGF signaling for skeleton formation was first discovered by the analysis of genetic FGFR mutations which cause several bone morphogenetic disorders, including achondroplasia, the most common form of human dwarfism. The formation of the long bones is mediated through proliferation and differentiation of highly specialized cells - chondrocytes. Chondrocytes respond to FGF with growth inhibition, a unique response which differs from the proliferative response of the majority of cell types; however its molecular determinants are still unclear...
March 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28298438/single-cell-analysis-reveals-lineage-segregation-in-early-post-implantation-mouse-embryos
#7
Jing Wen, Yanwu Zeng, Zhuoqing Fang, Junjie Gu, Laixiang Ge, Fan Tang, Zepeng Qu, Jing Hu, Yaru Cui, Kunshan Zhang, Junbang Wang, Siguang Li, Yi Sun, Ying Jin
The mammalian post-implantation embryo has been extensively investigated at the tissue level. However, to unravel the molecular basis for the cell-fate plasticity and determination, it is essential to study the characteristics of individual cells. Especially, the individual definitive endoderm (DE) cells have not been characterized in vivo. Here, we report gene expression patterns in single cells freshly isolated from mouse embryos on days 5.5 and 6.5. Initial transcriptome data from 124 single cells yielded signature genes for the epiblast, visceral endoderm, and extra-embryonic ectoderm and revealed a unique distribution pattern of fibroblast growth factor (Fgf) ligands and receptors...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28295855/recovery-of-shape-and-size-in-a-developing-organ-pair
#8
Amelia A Green, Kishore R Mosaliganti, Ian A Swinburne, Nikolaus D Obholzer, Sean G Megason
BACKGROUND Paired organs in animals are largely bilaterally symmetric despite inherent noise in most biological processes. How is precise organ shape and size achieved during development despite this noise? Examining paired organ development is a challenge because it requires repeated quantification of two structures in parallel within living embryos. Here we combine bilateral quantification of morphology through time with asymmetric perturbations to study regulation of organ shape, size and symmetry in developing organ pairs...
March 13, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28294563/a-new-material-for-tissue-engineered-vagina-reconstruction-acellular-porcine-vagina-matrix
#9
Jing-Kun Zhang, Run-Xuan Du, Lin Zhang, Ya-Nan Li, Ming-le Zhang, Shuo Zhao, Xiang-Hua Huang, Yan-Fang Xu
Acellular matrix materials have been widely used to repair various tissues and organs. According to the plastic principle, when a part of the body is lost, it should be replaced with a similar material. Therefore, the use of a homologous organ-specific acellular vaginal tissue in vagina reconstruction repair surgery may show good results. However, the acellular vagina matrix (AVM) form large vertebrates is difficult to isolate. In this study, we described a multi-step method to prepare porcine AVM and evaluated the efficacy of acellularization...
March 10, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28293196/muscle-sympathetic-nerve-activity-is-associated-with-liver-insulin-sensitivity-in-obese-non-diabetic-men
#10
Daniel L T Chen, Rachael Brown, Carsten Liess, Anne Poljak, Aimin Xu, Jialiang Zhang, Michael Trenell, Arthur Jenkins, Donald Chisholm, Dorit Samocha-Bonet, Vaughan G Macefield, Jerry R Greenfield
Introduction: Muscle sympathetic nerve activity (MSNA) may play a role in insulin resistance in obesity. However, the direction and nature of the relationship between MSNA and insulin resistance in obesity remain unclear. We hypothesized that resting MSNA would correlate inversely with both muscle and liver insulin sensitivity and that it would be higher in insulin-resistant vs. insulin-sensitive subjects. Materials and methods: Forty-five non-diabetic obese subjects were studied. As no significant relationships were found in women, the data presented in on 22 men aged 48 ± 12 years...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28290186/phosphorus-and-other-aspects-of-ckd-mbd-in-the-conservative-management-of-chronic-kidney-disease
#11
Anuja Shah
As the prevalence of chronic kidney disease (CKD) increases and the population ages, there is an imperative to offer cost effective and patient specific therapeutic options for the management of advanced CKD. In cases where there is a desire to avoid or delay renal replacement therapy, conservative options need to be defined and strategies for delaying the need for renal replacement therapy should be offered. CKD-mineral bone disorders (MBD) refers to the constellation of disturbances in abnormal bone and soft tissue calcification along with abnormalities, in phosphorus, calcium, parathyroid hormone, vitamin D, and FGF-23...
June 2017: Panminerva Medica
https://www.readbyqxmd.com/read/28289333/influence-of-vaginal-lactoferrin-administration-on-amniotic-fluid-cytokines-and-its-role-against-inflammatory-complications-of-pregnancy
#12
Martina Maritati, Manola Comar, Nunzia Zanotta, Silva Seraceni, Alessandro Trentini, Fabrizio Corazza, Fortunato Vesce, Carlo Contini
BACKGROUND: An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors. METHODS: Sixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28289136/estrogen-modulates-mesenchymal-epidermal-interactions-in-the-adult-nipple
#13
Hsing-Jung Wu, Ji Won Oh, Dan F Spandau, Sunil Tholpady, Jesus Diaz, Laura J Schroeder, Carlos D Offutt, Adam B Glick, Maksim V Plikus, Sachiko Koyama, John Foley
Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, specific pathways involved remain to be identified. By recombining cells from ventral skin of the K14-PTHrP transgenic mice with those from wild-type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially-expressed transcripts of the WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28289135/the-chromatin-modifier-satb1-regulates-cell-fate-through-fgf-signalling-in-the-early-mouse-embryo
#14
Mubeen Goolam, Magdalena Zernicka-Goetz
The separation of embryonic from extra-embryonic tissues within the inner-cell-mass (ICM) to generate the epiblast (EPI), that will form the new organism, from the primitive endoderm (PE), that will form the yolk sac, is a crucial developmental decision. Here we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos with higher expression levels in the ICM progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE...
March 13, 2017: Development
https://www.readbyqxmd.com/read/28287551/temporal-ordering-of-dynamic-expression-data-from-detailed-spatial-expression-maps
#15
Charlotte S L Bailey, Robert A Bone, Philip J Murray, J Kim Dale
During somitogenesis, pairs of epithelial somites form in a progressive manner, budding off from the anterior end of the pre-somitic mesoderm (PSM) with a strict species-specific periodicity. The periodicity of the process is regulated by a molecular oscillator, known as the "segmentation clock," acting in the PSM cells. This clock drives the oscillatory patterns of gene expression across the PSM in a posterior-anterior direction. These so-called clock genes are key components of three signaling pathways: Wnt, Notch, and fibroblast growth factor (FGF)...
February 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28287406/mesothelin-mucin-16-signaling-in-activated-portal-fibroblasts-regulates-cholestatic-liver-fibrosis
#16
Yukinori Koyama, Ping Wang, Shuang Liang, Keiko Iwaisako, Xiao Liu, Jun Xu, Mingjun Zhang, Mengxi Sun, Min Cong, Daniel Karin, Kojiro Taura, Chris Benner, Sven Heinz, Tapan Bera, David A Brenner, Tatiana Kisseleva
Cholestatic liver fibrosis is caused by obstruction of the biliary tract and is associated with early activation of portal fibroblasts (PFs) that express Thy-1, fibulin 2, and the recently identified marker mesothelin (MSLN). Here, we have demonstrated that activated PFs (aPFs) and myofibroblasts play a critical role in the pathogenesis of liver fibrosis induced by bile duct ligation (BDL). Conditional ablation of MSLN+ aPFs in BDL-injured mice attenuated liver fibrosis by approximately 50%. Similar results were observed in MSLN-deficient mice (Msln-/- mice) or mice deficient in the MSLN ligand mucin 16 (Muc16-/- mice)...
March 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28283405/coordination-of-limb-development-by-crosstalk-among-axial-patterning-pathways
#17
REVIEW
Irene Delgado, Miguel Torres
Vertebrate limb development relies on the activity of signaling centers that promote growth and control patterning along three orthogonal axes of the limb bud. The apical ectodermal ridge, at the distal rim of the limb bud ectoderm, produces WNT and FGF signals, which promote limb bud growth and progressive distalization. The zone of polarizing activity, a discrete postero-distal mesenchymal domain, produces SHH, which stimulates growth and organizes patterning along the antero-posterior axis. The dorsal and ventral ectoderms produce, respectively, WNT7A and BMPs, which induce dorso-ventral limb fates...
March 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28276325/ferric-carboxymaltose-induced-hypophosphataemia-after-kidney-transplantation
#18
V Sari, R Atiqi, E J Hoorn, A C Heijboer, T van Gelder, D A Hesselink
BACKGROUND: Ferric carboxymaltose (FCM) can induce hypophosphataemia in the general population and patients with chronic kidney disease (CKD). Less is known about the effect of FCM in the kidney transplant population. It has been suggested that fibroblast growth factor 23 (FGF-23)-mediated renal phosphate wasting may be the most likely cause of this phenomenon. In the current study, the effects of FCM on phosphate metabolism were studied in a cohort of kidney transplant recipients. METHODS: Two index patients receiving FCM are described...
March 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28276279/the-immune-stimulation-capacity-of-liposome-treated-red-blood-cells
#19
Luciana da Silveira Cavalcante, Donald R Branch, Trang T Duong, Rae S M Yeung, Jason P Acker, Jelena L Holovati
Our in vivo studies on a rat model established safety of transfusing liposome-treated red blood cells (RBCs) but identified the potential for immune modulation as related to transfusion efficacy of liposome-treated RBCs. The aim of this study was at assessing the impact of liposome-induced membrane changes on the immune profile of liposome-treated RBCs by (a) evaluating their interaction with endothelial cells and monocytes; and (b) the resulting immune response derived from this interaction, in the form of cytokine release, adhesion molecules expression and phagocytosis...
March 9, 2017: Journal of Liposome Research
https://www.readbyqxmd.com/read/28275113/potential-mechanisms-of-effects-of-serum-derived-bovine-immunoglobulin-protein-isolate-therapy-in-patients-with-diarrhea-predominant-irritable-bowel-syndrome
#20
Nelson Valentin, Michael Camilleri, Paula Carlson, Sean C Harrington, Deborah Eckert, Jessica O'Neill, Duane Burton, Jun Chen, Audrey L Shaw, Andres Acosta
Serum-derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open-label study in 15 patients with irritable bowel syndrome-diarrhea (IBS-D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability ((13)C-mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF-19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa...
March 2017: Physiological Reports
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