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https://www.readbyqxmd.com/read/28214040/reinforcement-of-intestinal-epithelial-barrier-by-arabinoxylans-in-overweight-and-obese-subjects-a-randomized-controlled-trial-arabinoxylans-in-gut-barrier
#1
Bouke N Salden, Freddy J Troost, Ellen Wilms, Pilar Truchado, Ramiro Vilchez-Vargas, Dietmar H Pieper, Ruy Jáuregui, Massimo Marzorati, Tom van de Wiele, Sam Possemiers, Ad A Masclee
BACKGROUND & AIMS: Obesity and metabolic diseases are associated with alterations in microbial composition and impaired gut barrier. Previous in vitro and animal studies have shown that arabinoxylans (AX) have the potential to modulate gut microbiota and gut barrier and therefore could have a protective role. Primary aim of the study was to investigate the effect of AX on intestinal permeability. Secondary aims included the effect of AX on gene transcription and protein expression of tight junctions (TJ), intestinal microbiota composition and activity, immune response and metabolic markers in overweight and obese individuals...
February 3, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28213979/mmp-2-and-mmp-14-silencing-inhibits-vegfr2-cleavage-and-induces-the-differentiation-of-porcine-adipose-derived-mesenchymal-stem-cells-to-endothelial-cells
#2
Sami G Almalki, Yovani Llamas Valle, Devendra K Agrawal
The molecular mechanisms that control the ability of adipose-derived mesenchymal stem cells (AMSCs) to remodel three-dimensional extracellular matrix barriers during differentiation are not clearly understood. Herein, we studied the expression of matrix metalloproteinases (MMPs) during the differentiation of AMSCs to endothelial cells (ECs) in vitro. MSCs were isolated from porcine abdominal adipose tissue, and characterized by immunopositivity to CD44, CD90, CD105, and immunonegativity to CD14 and CD45. Plasticity of AMSCs was confirmed by multilineage differentiation...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213970/efficacy-and-safety-of-immuno-magnetically-sorted-smooth-muscle-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-for-restoring-urethral-sphincter-function
#3
Yanhui Li, Morgaine Green, Yan Wen, Yi Wei, Prachi Wani, Zhe Wang, Renee Reijo Pera, Bertha Chen
Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical-scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC-derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence-activated cell sorting (FACS) which is not practical for autologous clinical applications...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213967/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-improve-survival-from-lethal-hepatic-failure-in-mice
#4
Hiroaki Haga, Irene K Yan, Kenji Takahashi, Akiko Matsuda, Tushar Patel
Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α)...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213379/slowed-decay-of-mrnas-enhances-platelet-specific-translation
#5
Eric W Mills, Rachel Green, Nicholas T Ingolia
Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of mRNAs, ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA-Seq and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro derived MK cells and these platelet-enriched transcripts are broadly occupied by ribosomes...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#6
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213099/polymeric-nanoparticles-loaded-with-dexamethasone-or-%C3%AE-tocopheryl-succinate-to-prevent-cisplatin-induced-ototoxicity
#7
Sergio Martín-Saldaña, Raquel Palao-Suay, María Rosa Aguilar, Rafael Ramírez-Camacho, Julio San Román
: The aim of this work is the development of highly protective agents to be administered locally within the middle ear to avoid cisplatin-induced ototoxicity, which affects to 100% of the clinical patients at ultra-high concentrations (16 mg/kg). The protective agents are based on polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate as anti-inflammarory and anti-apoptotic molecules. Dexamethasone and α-tocopheryl succinate are poorly soluble in water and present severe side effects when systemic administered during long periods of time...
February 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28211365/converging-biofabrication-and-organoid-technologies-the-next-frontier-in-hepatic-and-intestinal-tissue-engineering
#8
Kerstin Schneeberger, Bart Spee, Pedro Costa, Norman Sachs, Hans Clevers, Jos Malda
Adult tissue stem cells can form self-organizing 3D organoids in vitro. Organoids resemble small units of their organ of origin and have great potential for tissue engineering, as well as models of disease. However, current culture technology limits the size, architecture and complexity of organoids. Here, we review the establishment of intestinal and hepatic organoids and discuss how the convergence of organoids and biofabrication technologies can help overcome current limitations, and thereby further advance the translational application of organoids in tissue engineering and regenerative medicine...
February 17, 2017: Biofabrication
https://www.readbyqxmd.com/read/28211215/zkscan1-gene-and-its-related-circular-rna-circzkscan1-both-inhibit-hepatocellular-carcinoma-cell-growth-migration-and-invasion-but-through-different-signaling-pathways
#9
Zhicheng Yao, Jingyan Luo, Kunpeng Hu, Jizong Lin, He Huang, Qiangliang Wang, Peng Zhang, Zhiyong Xiong, Zejian Huang, Chonghua He, Bo Liu, Yang Yang
There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development, but the regulation and function of human circRNAs remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P<0.05) in the HCC samples compared with that in matched adjacent non-tumorous tissues by reverse transcription PCR (RT-PCR)...
February 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28210258/human-gingiva-derived-mesenchymal-stem-cells-inhibit-xeno-graft-versus-host-disease-via-cd39-cd73-adenosine-and-ido-signals
#10
Feng Huang, Maogen Chen, Weiqian Chen, Jian Gu, Jia Yuan, Yaoqiu Xue, Junlong Dang, Wenru Su, Julie Wang, Homayoun H Zadeh, Xiaoshun He, Limin Rong, Nancy Olsen, Song Guo Zheng
Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209709/pathogenic-mutations-in-retinitis-pigmentosa-2-predominantly-result-in-loss-of-rp2-protein-stability-in-human-and-zebrafish
#11
Fei Liu, Yayun Qin, Shanshan Yu, Dinesh C Soares, Lifang Yang, Jun Weng, Chang Li, Meng Gao, Zhaojing Lu, Xuebin Hu, Xiliang Liu, Tao Jiang, Jing Y Liu, Xinhua Shu, Zhaohui Tang, Mugen Liu
Mutations in retinitis pigmentosa 2 (RP2) account for 10-20% of X-linked retinitis pigmentosa (RP) cases. The encoded RP2 protein is implicated in ciliary trafficking of myristoylated and prenylated proteins in photoreceptor cells. To date, over 70 mutations in RP2 have been identified. How these mutations disrupt the function of RP2 is not fully understood. Here, we report a novel in-frame 12-bp deletion (c.357_368del, p.Pro120_Gly123del) in zebrafish rp2 The mutant zebrafish shows reduced rod phototransduction proteins and progressive retinal degeneration...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209156/breastdefend-enhances-effect-of-tamoxifen-in-estrogen-receptor-positive-human-breast-cancer-in-vitro-and-in-vivo
#12
Shujie Cheng, Victor Castillo, Matt Welty, Mark Alvarado, Isaac Eliaz, Constance J Temm, George E Sandusky, Daniel Sliva
BACKGROUND: Tamoxifen (TAM) has been widely used for the treatment of estrogen receptor (ER)-positive breast cancer and its combination with other therapies is being actively investigated as a way to increase efficacy and decrease side effects. Here, we evaluate the therapeutic potential of co-treatment with TAM and BreastDefend (BD), a dietary supplement formula, in ER-positive human breast cancer. METHODS: Cell proliferation and apoptosis were determined in ER-positive human breast cancer cells MCF-7 by MTT assay, quantitation of cytoplasmic histone-associated DNA fragments and expression of cleaved PARP, respectively...
February 16, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28208632/cross-talk-between-dnmt2-dependent-trna-methylation-and-queuosine-modification
#13
REVIEW
Ann E Ehrenhofer-Murray
Enzymes of the Dnmt2 family of methyltransferases have yielded a number of unexpected discoveries. The first surprise came more than ten years ago when it was realized that, rather than being DNA methyltransferases, Dnmt2 enzymes actually are transfer RNA (tRNA) methyltransferases for cytosine-5 methylation, foremost C38 (m5C38) of tRNAAsp. The second unanticipated finding was our recent discovery of a nutritional regulation of Dnmt2 in the fission yeast Schizosaccharomyces pombe. Significantly, the presence of the nucleotide queuosine in tRNAAsp strongly stimulates Dnmt2 activity both in vivo and in vitro in S...
February 10, 2017: Biomolecules
https://www.readbyqxmd.com/read/28205560/alkb-homolog-3-mediated-trna-demethylation-promotes-protein-synthesis-in-cancer-cells
#14
Yuko Ueda, Ikumi Ooshio, Yasuyuki Fusamae, Kaori Kitae, Megumi Kawaguchi, Kentaro Jingushi, Hiroaki Hase, Kazuo Harada, Kazumasa Hirata, Kazutake Tsujikawa
The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205428/systemically-infused-mesenchymal-stem-cells-show-different-homing-profiles-in-healthy-and-tumor-mouse-models
#15
Chengying Xie, Zhangru Yang, Yuanzhen Suo, Qianqian Chen, Dan Wei, Xiaofu Weng, Zhengqin Gu, Xunbin Wei
Bone marrow-derived mesenchymal stem cells (MSCs) can localize in injured, inflamed, and cancerous tissues after systemic infusion. However, the dynamic homing profile of MSCs in the peripheral blood is not well characterized. Here, using in vivo flow cytometry to noninvasively monitor the dynamics of fluorescence-labeled cells, we found different clearance kinetics of systemically infused MSCs between healthy and tumor mouse models. The circulation times of MSCs in healthy mice and mice with subcutaneous tumors, orthotopically transplanted liver tumors, or metastatic lung tumors were 30, 24, 18, and 12 hours, respectively, suggesting that MSCs actively home to tumor environments...
February 16, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205406/potency-of-human-cardiosphere-derived-cells-from-patients-with-ischemic-heart-disease-is-associated-with-robust-vascular-supportive-ability
#16
Emma Harvey, Huajun Zhang, Pilar Sepúlveda, Sara P Garcia, Dominic Sweeney, Fizzah A Choudry, Delia Castellano, George N Thomas, Hassan Kattach, Romina Petersen, Derek J Blake, David P Taggart, Mattia Frontini, Suzanne M Watt, Enca Martin-Rendon
Cardiosphere-derived cell (CDC) infusion into damaged myocardium has shown some reparative effect; this could be improved by better selection of patients and cell subtype. CDCs isolated from patients with ischemic heart disease are able to support vessel formation in vitro but this ability varies between patients. The primary aim of our study was to investigate whether the vascular supportive function of CDCs impacts on their therapeutic potential, with the goal of improving patient stratification. A subgroup of patients produced CDCs which did not efficiently support vessel formation (poor supporter CDCs), had reduced levels of proliferation and increased senescence, despite them being isolated in the same manner and having a similar immunophenotype to CDCs able to support vessel formation...
February 16, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205128/heat-shock-protein-70-protects-cardiomyocytes-through-suppressing-sumoylation-and-nucleus-translocation-of-phosphorylated-eukaryotic-elongation-factor-2-during-myocardial-ischemia-and-reperfusion
#17
Chao Zhang, Xiaojuan Liu, Jin Miao, Shengcun Wang, Liucheng Wu, Daliang Yan, Jingjing Li, Wanwan Guo, Xiang Wu, Aiguo Shen
Myocardial ischemia and reperfusion (MIR) results in cardiomyocyte apoptosis with severe outcomes, which blocks cardiac tissue recovering from myocardial ischemia diseases. Heat shock protein 70 (HSP70) is one of protective molecule chaperones which could regulate the nucleus translocation of other proteins. In addition, eukaryotic elongation factor 2 (eEF2), which modulates protein translation process, is vital to the recovery of heart during MIR. However, the relationship between HSP70 and eEF2 and its effects on MIR are unclear...
February 15, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28204820/hypoxia-enhances-the-wound-healing-potential-of-adipose-derived-stem-cells-in-a-novel-human-primary-keratinocyte-based-scratch-assay
#18
Simone Riis, Rhonda Newman, Hilal Ipek, Jens I Andersen, David Kuninger, Shayne Boucher, Mohan C Vemuri, Cristian P Pennisi, Vladimir Zachar, Trine Fink
Preclinical studies have suggested that paracrine factors from adipose-derived stem cells (ASCs) promote the healing of chronic wounds, and that the exposure of ASCs to hypoxia enhances their wound healing effect. To aid the translation of these findings into clinical use, robust wound models are necessary to explore each aspect of wound healing. The aspect of re-epithelization is often studied in a scratch assay based on transformed keratinocytes. However, there are concerns regarding the validity of this model, since these cell lines differ from normal keratinocytes, both in terms of proliferative capacity and differentiation, and sensitivity to environmental cues...
February 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202547/post-translational-activation-of-glutamate-cysteine-ligase-with-dimercaprol-a-novel-mechanism-of-inhibiting-neuroinflammation-in-vitro
#19
Pallavi B McElroy, Ashwini Sri Hari, Brian J Day, Manisha Patel
Neuroinflammation and oxidative stress are hallmarks of various neurological diseases. However, whether and how the redox processes control neuroinflammation is incompletely understood. We hypothesized that increasing cellular glutathione (GSH) levels would inhibit neuroinflammation. A series of thiol compounds were identified to elevate cellular GSH levels by a novel approach i.e. post-translational activation of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH biosynthesis. These small thiolcontaining compounds were examined for their ability to increase intracellular GSH levels in a murine microglial cell line (BV2), of which dimercaprol [2,3-dimercapto-1-propanol (DMP)] was found to be the most effective compound...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28202491/organoid-technologies-meet-genome-engineering
#20
REVIEW
Jing Nie, Eri Hashino
Three-dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two-dimensional (2D) cell culture models. Organoids, the 3D self-organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications...
February 15, 2017: EMBO Reports
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