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https://www.readbyqxmd.com/read/28641308/detection-of-phosphatidylserine-positive-exosomes-for-the-diagnosis-of-early-stage-malignancies
#1
Raghava Sharma, Xianming Huang, Rolf A Brekken, Alan J Schroit
BACKGROUND: There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. METHODS: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641303/microrna-122a-regulates-zonulin-by-targeting-egfr-in-intestinal-epithelial-dysfunction
#2
Bin Zhang, Yinghai Tian, Ping Jiang, Yanqiong Jiang, Chao Li, Ting Liu, Rujian Zhou, Ning Yang, Xinke Zhou, Zhihua Liu
BACKGROUND/AIMS: This study aimed to investigate the role of microRNA (miR)-122a in regulating zonulin during the modulation of intestinal barrier. METHODS: Zonulin proteins and their target gene expression were analyzed in miR-122a-overexpressing cell lines and in the target gene of epidermal growth factor receptor (EGFR). An mmu-miR-122a intestinal epithelial conditional transgenic (miR-122a-TG) mouse model was established to investigate EGFR and zonulin expression...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28641286/effect-of-bexarotene-on-platelet-activation-and-apoptosis
#3
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28641141/rag2-involves-the-ig%C3%AE%C2%BA-locus-demethylation-during-b-cell-development
#4
Caijun Wu, Yanying Dong, Xiaohui Zhao, Ping Zhang, Mingzhe Zheng, Hua Zhang, Shichang Li, Yaofeng Jin, Yunfeng Ma, Huixun Ren, Yanhong Ji
The genes encoding the immunoglobulin κ light chain are assembled during B cell development by V(D)J recombination. For efficient rearrangement, the Igκ locus must undergo a series of epigenetic changes. One such epigenetic mark is DNA methylation. The mechanism that the Igκ locus is selectively demethylated at the pre-B cell stage has not previously been characterized. Here, we employed bisulfite DNA-modification assays to analyze the methylation status of the Igκ locus in primary pre-B cells from RAG-deficient mice with pre-rearranged Igh knock-in allele...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28641136/age-exacerbates-abnormal-protein-expression-in-a-mouse-model-of-down-syndrome
#5
Md Mahiuddin Ahmed, Aaron Block, Suhong Tong, Muriel T Davisson, Katheleen J Gardiner
The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease...
May 10, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#6
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28641076/elevated-cd26-expression-by-skin-fibroblasts-distinguishes-a-profibrotic-phenotype-involved-in-scar-formation-compared-to-gingival-fibroblasts
#7
Wesley Mah, Guoqiao Jiang, Dylan Olver, Corrie Gallant-Behm, Colin Wiebe, David A Hart, Leeni Koivisto, Hannu Larjava, Lari Häkkinen
Compared to skin, wound healing in oral mucosa is faster and produces less scarring, but the mechanisms involved are incompletely understood. Studies in mice have linked high expression of CD26 to a profibrotic fibroblast phenotype, but this has not been tested in models more relevant for humans. We hypothesized that CD26 is highly expressed by human skin fibroblasts (SFBLs), and this associates with a profibrotic phenotype distinct from gingival fibroblasts (GFBLs). We compared CD26 expression in human gingiva and skin and in gingival and hypertrophic-like scar-forming skin wound healing in a pig model, and used three-dimensional cultures of human GFBLs and SFBLs...
June 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28641008/hypoxia-induced-changes-in-the-fibroblast-secretome-exosome-and-whole-cell-proteome-using-cultured-cardiac-derived-cells-isolated-from-neonatal-mice
#8
Jake Cosme, Hongbo Guo, Sina Hadipour-Lakmehsari, Andrew Emili, Anthony O Gramolini
Cardiac fibroblasts (CF) represent a major subpopulation of cells in the developing and adult heart. Cardiomyocyte (CM) and CF intercellular communication occurs through paracrine interactions and modulate myocyte development and stress response. Detailed proteomic analysis of the CF secretome in normal and stressed conditions may offer insights into the role of CF in heart development and disease. Primary neonatal mouse CF were isolated and cultured for 24h in 21% (normoxic) or 2% (hypoxic) O2. Conditioned media was separated to obtain EXO and EXO-depleted secretome fractions...
June 22, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28640969/control-of-breathing-and-ventilatory-acclimatization-to-hypoxia-in-deer-mice-native-to-high-altitudes
#9
Catherine M Ivy, Graham R Scott
AIM: We compared the control of breathing and heart rate by hypoxia between high- and low-altitude populations of Peromyscus mice, to help elucidate the physiological specializations that help high-altitude natives cope with O2 limitation. METHODS: Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were bred in captivity at sea level. The F1 progeny of each population were raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa, simulating hypoxia at ~4300 m) for 5 months...
June 22, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28640957/restoration-of-cutaneous-pigmentation-by-transplantation-to-mice-of-isogeneic-human-melanocytes-in-dermal-epidermal-engineered-skin-substitutes
#10
Steven T Boyce, Christopher M Lloyd, Mark C Kleiner, Viki B Swope, Zalfa Abdel-Malek, Dorothy M Supp
Autologous engineered skin substitutes (ESS) containing melanocytes (hM) may restore pigmentation, and photoprotection after grafting to full-thickness skin wounds. In the current study, normal hM were isolated from discard skin, propagated with or without tyrosinase inhibitors, cryopreserved, recovered into culture, and added to ESS (ESS-P) before transplantation. ESS-P were incubated in either UCMC160/161 or UCDM1 medium, scored for hM densities, and grafted to mice. The results showed that: sufficient hM can be propagated to expand donor tissue by 100-fold; incubation of hM in tyrosinase inhibitors reduced pigment levels but did not change hM recovery after cryopreservation; hM densities in ESS-P were greater after incubation in UCDM1 than UCMC160 medium; hM were localized to the dermal-epidermal junction of ESS-P; and UCDM1 medium promoted earlier pigment distribution and density...
June 22, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28640904/correlation-of-disease-severity-with-body-weight-and-high-fat-diet-in-the-fatzo-pco-mouse
#11
Brian A Droz, Bria L Sneed, Charles V Jackson, Karen M Zimmerman, M Dodson Michael, Paul J Emmerson, Tamer Coskun, Richard G Peterson
Obesity in many current pre-clinical animal models of obesity and diabetes is mediated by monogenic mutations; these are rarely associated with the development of human obesity. A new mouse model, the FATZO mouse, has been developed to provide polygenic obesity and a metabolic pattern of hyperglycemia and hyperinsulinemia, that support the presence of insulin resistance similar to metabolic disease in patients with insulin resistance/type 2 diabetes. The FATZO mouse resulted from a cross of C57BL/6J and AKR/J mice followed by selective inbreeding for obesity, increased insulin and hyperglycemia...
2017: PloS One
https://www.readbyqxmd.com/read/28640866/diet-induced-adipose-tissue-expansion-is-mitigated-in-mice-with-a-targeted-inactivation-of-mesoderm-specific-transcript-mest
#12
Rea P Anunciado-Koza, Justin Manuel, Randall L Mynatt, Jingying Zhang, Leslie P Kozak, Robert A Koza
Interindividual variation of white adipose tissue (WAT) expression of mesoderm specific transcript (Mest), a paternally-expressed imprinted gene belonging to the α/β-hydrolase fold protein family, becomes apparent among genetically inbred mice fed high fat diet (HFD) and is positively associated with adipose tissue expansion (ATE). To elucidate a role for MEST in ATE, mice were developed with global and adipose tissue inactivation of Mest. Mice with homozygous (MestgKO) and paternal allelic (MestpKO) inactivation of Mest were born at expected Mendelian frequencies, showed no behavioral or physical abnormalities, and did not perturb expression of the Mest locus-derived microRNA miR-335...
2017: PloS One
https://www.readbyqxmd.com/read/28640864/targeting-breast-cancer-cells-by-mrs1477-a-positive-allosteric-modulator-of-trpv1-channels
#13
Mustafa Nazıroğlu, Bilal Çiğ, Walter Blum, Csaba Vizler, Andrea Buhala, Annamária Marton, Róbert Katona, Katalin Jósvay, Beat Schwaller, Zoltán Oláh, László Pecze
There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28640861/inhibition-of-nf-%C3%AE%C2%BAb-improves-the-stress-resistance-and-myogenic-differentiation-of-mdspcs-isolated-from-naturally-aged-mice
#14
Jonathan D Proto, Aiping Lu, Akaitz Dorronsoro, Alex Scibetta, Paul D Robbins, Laura J Niedernhofer, Johnny Huard
A decline in the regenerative capacity of adult stem cells with aging is well documented. As a result of this decline, the efficacy of autologous stem cell therapies is likely to decline with increasing donor age. In these cases, strategies to restore the function of aged stem cells would have clinical utility. Globally, the transcription factor NF-κB is up-regulated in aged tissues. Given the negative role that NF-κB plays in myogenesis, we investigated whether the age-related decline in the function of muscle-derived stem/progenitor cells (MDSPCs) could be improved by inhibition of NF-κB...
2017: PloS One
https://www.readbyqxmd.com/read/28640857/glucose-dysregulation-and-response-to-common-anti-diabetic-agents-in-the-fatzo-pco-mouse
#15
Richard G Peterson, Charles Van Jackson, Karen M Zimmerman, Jorge Alsina-Fernandez, M Dodson Michael, Paul J Emmerson, Tamer Coskun
The FATZO/Pco mouse is the result of a cross of the C57BL/6J and AKR/J strains. The crossing of these two strains and the selective inbreeding for obesity, insulin resistance and hyperglycemia has resulted in an inbred strain exhibiting obesity in the presumed presence of an intact leptin pathway. Routinely used rodent models for obesity and diabetes research have a monogenic defect in leptin signaling that initiates obesity. Given that obesity and its sequelae in humans are polygenic in nature and not associated with leptin signaling defects, the FATZO mouse may represent a more translatable rodent model for study of obesity and its associated metabolic disturbances...
2017: PloS One
https://www.readbyqxmd.com/read/28640850/no-evidence-for-punishment-in-communally-nursing-female-house-mice-mus-musculus-domesticus
#16
Manuela Ferrari, Barbara König
Punishment is claimed as an important mechanism to stabilise costly cooperation in humans, but its importance in social animals has been questioned recently due to both conceptual considerations and a lack of empirical evidence (only few published studies). We empirically tested whether there is evidence for punishment in communally nursing house mice (Mus musculus domesticus, direct descendants of "wild" animals). Communally breeding females pool their litters and raise all offspring together, indiscriminately caring for own and other offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28640846/endothelial-angiogenesis-is-directed-by-runx1t1-regulated-vegfa-bmp4-and-tgf-%C3%AE-2-expression
#17
Ko-Hsun Liao, Shing-Jyh Chang, Hsin-Chuan Chang, Chen-Li Chien, Tse-Shun Huang, Te-Chia Feng, Wen-Wei Lin, Chuan-Chi Shih, Muh-Hwa Yang, Shung-Haur Yang, Chi-Hung Lin, Wei-Lun Hwang, Oscar K Lee
Tissue angiogenesis is intimately regulated during embryogenesis and postnatal development. Defected angiogenesis contributes to aberrant development and is the main complication associated with ischemia-related diseases. We previously identified the increased expression of RUNX1T1 in umbilical cord blood-derived endothelial colony-forming cells (ECFCs) by gene expression microarray. However, the biological relevance of RUNX1T1 in endothelial lineage is not defined clearly. Here, we demonstrate RUNX1T1 regulates the survival, motility and tube forming capability of ECFCs and EA...
2017: PloS One
https://www.readbyqxmd.com/read/28640832/sarpogrelate-hydrochloride-ameliorates-diabetic-nephropathy-associated-with-inhibition-of-macrophage-activity-and-inflammatory-reaction-in-db-db-mice
#18
Eun Soo Lee, Mi Young Lee, Mi-Hye Kwon, Hong Min Kim, Jeong Suk Kang, You Mi Kim, Eun Young Lee, Choon Hee Chung
The aim of this study was to evaluate the effects of sarpogrelate hydrochloride (SH), a selective serotonin 2A receptor antagonist, on diabetic nephropathy in a type 2 diabetes mouse model. We treated db/m and db/db mice with SH (30 mg/kg/day) for 12 weeks. Rat renal proximal tubule cells (NRK-52E) and mouse macrophages (Raw 264.7) were stimulated by high glucose (30 mM glucose) or LPS (100 ng/ml) with or without SH (20 μM). We found that SH treatment increased serum adiponectin level and decreased urinary albumin, macrophage infiltration to glomeruli, and renal inflammatory and fibrosis signals, which were highly expressed in diabetic mice...
2017: PloS One
https://www.readbyqxmd.com/read/28640817/an-r-camp1-07-reporter-mouse-for-cell-type-specific-expression-of-a-sensitive-red-fluorescent-calcium-indicator
#19
Philipp Bethge, Stefano Carta, Dayra A Lorenzo, Ladan Egolf, Despoina Goniotaki, Linda Madisen, Fabian F Voigt, Jerry L Chen, Bernard Schneider, Masamichi Ohkura, Junichi Nakai, Hongkui Zeng, Adriano Aguzzi, Fritjof Helmchen
Genetically encoded calcium indicators (GECIs) enable imaging of in vivo brain cell activity with high sensitivity and specificity. In contrast to viral infection or in utero electroporation, indicator expression in transgenic reporter lines is induced noninvasively, reliably, and homogenously. Recently, Cre/tTA-dependent reporter mice were introduced, which provide high-level expression of green fluorescent GECIs in a cell-type-specific and inducible manner when crossed with Cre and tTA driver mice. Here, we generated and characterized the first red-shifted GECI reporter line of this type using R-CaMP1...
2017: PloS One
https://www.readbyqxmd.com/read/28640813/identification-of-a-sj%C3%A3-gren-s-syndrome-susceptibility-locus-at-oas1-that-influences-isoform-switching-protein-expression-and-responsiveness-to-type-i-interferons
#20
He Li, Tove Ragna Reksten, John A Ice, Jennifer A Kelly, Indra Adrianto, Astrid Rasmussen, Shaofeng Wang, Bo He, Kiely M Grundahl, Stuart B Glenn, Corinne Miceli-Richard, Simon Bowman, Sue Lester, Per Eriksson, Maija-Leena Eloranta, Johan G Brun, Lasse G Gøransson, Erna Harboe, Joel M Guthridge, Kenneth M Kaufman, Marika Kvarnström, Deborah S Cunninghame Graham, Ketan Patel, Adam J Adler, A Darise Farris, Michael T Brennan, James Chodosh, Rajaram Gopalakrishnan, Michael H Weisman, Swamy Venuturupalli, Daniel J Wallace, Kimberly S Hefner, Glen D Houston, Andrew J W Huang, Pamela J Hughes, David M Lewis, Lida Radfar, Evan S Vista, Contessa E Edgar, Michael D Rohrer, Donald U Stone, Timothy J Vyse, John B Harley, Patrick M Gaffney, Judith A James, Sean Turner, Ilias Alevizos, Juan-Manuel Anaya, Nelson L Rhodus, Barbara M Segal, Courtney G Montgomery, R Hal Scofield, Susan Kovats, Xavier Mariette, Lars Rönnblom, Torsten Witte, Maureen Rischmueller, Marie Wahren-Herlenius, Roald Omdal, Roland Jonsson, Wan-Fai Ng, Gunnel Nordmark, Christopher J Lessard, Kathy L Sivils
Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study...
June 22, 2017: PLoS Genetics
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