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https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#1
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28812211/the-immune-system-in-obesity-developing-paradigms-amidst-inconvenient-truths
#2
REVIEW
Madhur Agrawal, Philip A Kern, Barbara S Nikolajczyk
PURPOSE OF REVIEW: Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. RECENT FINDINGS: Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28811169/tissue-engineered-extracellular-matrices-ecms-in-urology-evolution-and-future-directions
#3
REVIEW
N F Davis, E M Cunnane, F J O'Brien, J J Mulvihill, M T Walsh
Autologous gastrointestinal tissue has remained the gold-standard reconstructive biomaterial in urology for >100 years. Mucus-secreting epithelium is associated with lifelong metabolic and neuromechanical complications when implanted into the urinary tract. Therefore, the availability of biocompatible tissue-engineered biomaterials such as extracellular matrix (ECM) scaffolds may provide an attractive alternative for urologists. ECMs are decellularised, biodegradable membranes that have shown promise for repairing defective urinary tract segments in vitro and in vivo by inducing a host-derived tissue remodelling response after implantation...
August 12, 2017: Surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland
https://www.readbyqxmd.com/read/28810629/inhibition-of-microrna-34a-ameliorates-murine-collagen-induced-arthritis
#4
Qiujie Dang, Fan Yang, Hongwei Lei, Xin Liu, Minglu Yan, He Huang, Xuemei Fan, Yang Li
Rheumatoid arthritis (RA) is one of the most frequently occurring autoimmne diseases, with symptoms including synovium hyperplasia, immune disorder, cartilage damage and bone resorption. It has previously been demonstrated that microRNA-34a (miR-34a) may participate in cell apoptosis, immune activation and bone metabolism, therefore the present study investigated the effects of miR-34a on RA. Collagen-induced arthritic (CIA) mice were employed as a murine model of experimental arthritis, and it was demonstrated that the level of miR-34a in the spleens, lymph nodes and synovium was increased in the CIA mice compared with normal DBA/1j mice...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807770/gsta1-genetic-variants-and-conditioning-regimen-missing-key-factors-in-dosing-guidelines-of-busulfan-in-pediatric-hematopoietic-stem-cell-transplantation
#5
T Nava, M A Rezgui, Crs Uppugunduri, P Huezo-Diaz Curtis, Y Théoret, M Duval, L E Daudt, M Ansari, M Krajinovic, H Bittencourt
Busulfan (Bu) is a key component of conditioning regimens used prior to hematopoietic stem cell transplantation (SCT) in children. Different predictive methods have been used to calculate the Bu first-dose. To evaluate the necessity of further improvements, we retrospectively analyzed the currently available weight- and age-based guidelines to calculate the first doses in 101 children who underwent allogenic SCT in CHU Sainte-Justine, Montreal, following an intravenous Bu-containing conditioning regimen according to genetic and clinical factors...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28806730/a-systems-approach-reveals-distinct-metabolic-strategies-among-the-nci-60-cancer-cell-lines
#6
Maike K Aurich, Ronan M T Fleming, Ines Thiele
The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models' capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates...
August 14, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28806133/autophagy-dictates-metabolism-and-differentiation-of-inflammatory-immune-cells
#7
Thomas Riffelmacher, Felix Clemens Richter, Anna Katharina Simon
The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. Particularly, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28805660/prolyl-hydroxylase-2-inactivation-enhances-glycogen-storage-and-promotes-excessive-neutrophilic-responses
#8
Pranvera Sadiku, Joseph A Willson, Rebecca S Dickinson, Fiona Murphy, Alison J Harris, Amy Lewis, David Sammut, Ananda S Mirchandani, Eilise Ryan, Emily R Watts, A A Roger Thompson, Helen M Marriott, David H Dockrell, Cormac T Taylor, Martin Schneider, Patrick H Maxwell, Edwin R Chilvers, Massimilliano Mazzone, Veronica Moral, Chris W Pugh, Peter J Ratcliffe, Christopher J Schofield, Bart Ghesquiere, Peter Carmeliet, Moira Kb Whyte, Sarah R Walmsley
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28803808/two-novel-mutations-p-ser160pro-and-p-arg472cys-causing-glucose-6-phosphate-isomerase-deficiency-are-associated-with-erythroid-dysplasia-and-inappropriately-suppressed-hepcidin
#9
Renata Mojzikova, Pavla Koralkova, Dusan Holub, Zuzana Saxova, Dagmar Pospisilova, Daniela Prochazkova, Petr Dzubak, Monika Horvathova, Vladimir Divoky
Glucose-6-phosphate isomerase (GPI) deficiency, a genetic disorder responsible for chronic nonspherocytic hemolytic anemia, is the second most common red blood cell glycolytic enzymopathy. We report three patients from two unrelated families of Czech and Slovak origin with macrocytic hemolytic anemia due to GPI deficiency. The first patient had 15% of residual GPI activity resulting from two new heterozygous missense mutations c.478T>C and c.1414C>T leading to substitutions p.(Ser160Pro) and p.(Arg472Cys)...
April 14, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28803538/pharmacokinetics-of-tafamidis-a-transthyretin-amyloidosis-drug-in-rats
#10
Kyeong-Ryoon Lee, Jong-Woo Jeong, Hun-Chan Hyun, Jang Eunseo, Sunjoo Ahn Ahn, Sungwook Choi, Sang Hoon Joo, Sung-Sub Kim, Tae-Sung Koo
1. We characterized the pharmacokinetics of tafamidis, a novel drug to treat transthyretin-related amyloidosis, in rats after intravenous and oral administration at doses of 0.3-3 mg/kg. In vitro Caco-2 cell permeability and liver microsomal stability, as well as in vivo tissue distribution and plasma protein binding were also examined. 2. After intravenous injection, systemic clearance (CL), volumes of distribution at steady state (Vss), and half-life (T½) remained unaltered as a function of dose, with values in the ranges of 6...
August 14, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28803347/melatonin-mitochondria-and-the-skin
#11
REVIEW
Andrzej T Slominski, Michal A Zmijewski, Igor Semak, Tae-Kang Kim, Zorica Janjetovic, Radomir M Slominski, Jaroslaw W Zmijewski
The skin being a protective barrier between external and internal (body) environments has the sensory and adaptive capacity to maintain local and global body homeostasis in response to noxious factors. An important part of the skin response to stress is its ability for melatonin synthesis and subsequent metabolism through the indolic and kynuric pathways. Indeed, melatonin and its metabolites have emerged as indispensable for physiological skin functions and for effective protection of a cutaneous homeostasis from hostile environmental factors...
August 12, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28802037/the-pi3k-pathway-in-human-disease
#12
REVIEW
David A Fruman, Honyin Chiu, Benjamin D Hopkins, Shubha Bagrodia, Lewis C Cantley, Robert T Abraham
Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28800584/expression-of-the-rna-binding-protein-rbp10-promotes-the-bloodstream-form-differentiation-state-in-trypanosoma-brucei
#13
Elisha Mugo, Christine Clayton
In nearly all eukaryotes, cellular differentiation is governed by changes in transcription, and stabilized by chromatin and DNA modification. Gene expression control in the pathogen Trypanosoma brucei, in contrast, relies almost exclusively on post-transcriptional mechanisms, so RNA binding proteins must assume the burden that is usually borne by transcription factors. T. brucei multiply in the blood of mammals as bloodstream forms, and in the midgut of Tsetse flies as procyclic forms. We show here that a single RNA-binding protein, RBP10, promotes the bloodstream-form trypanosome differentiation state...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28798389/the-mitochondrial-derived-peptides-humanins14g-and-small-humanin-like-peptide-2-exhibit-chaperone-like-activity
#14
Alan K Okada, Kazuki Teranishi, Fleur Lobo, J Mario Isas, Jialin Xiao, Kelvin Yen, Pinchas Cohen, Ralf Langen
Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798194/hyperglycemia-does-not-affect-antigen-specific-activation-and-cytolytic-killing-by-cd8-t-cells-in-vivo
#15
Asha Recino, Kerry Barkan, Graham Ladds, Anne Cooke, F Susan Wong, Maja Wallberg
Metabolism is of central importance to T cell survival and differentiation. It is well known that T cells cannot function in the absence of glucose, but it is less clear how they respond to excessive levels of glucose. In this study we investigated how increasing levels of glucose affect T cell-mediated immune responses. We examined the effects of increased levels of glucose on CD8(+) T cell behaviour in vitro by assessing activation and cytokine production, as well as oxygen consumption rate, extracellular acidification rate and intracellular signalling...
August 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28797668/salinity-stress-enhancing-basal-and-induced-immune-responses-in-striped-catfish-pangasianodon-hypophthalmus-sauvage
#16
Mélodie Schmitz, Tamar Ziv, Arie Admon, Sébastien Baekelandt, Syaghalirwa N M Mandiki, Maëlenn L'Hoir, Patrick Kestemont
In the Mekong Delta, striped catfish are faced with chronic salinity stress related to saltwater intrusion induced by global climatic changes. In this study, striped catfish juveniles were submitted to a prolonged salinity stress (up to 10ppt) over three weeks followed by infection with a virulent bacterial strain, Edwardsiella ictaluri. Osmoregulatory parameters were investigated. In addition, a label free quantitative proteomics workflow was performed on kidneys. The workflow consisted of an initial global profiling of relative peptide abundances (by LC/MS, peak area quantification based on extracted ion currents), followed by identification (by MS/MS)...
August 7, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28797581/surviving-stress-modulation-of-atf4-mediated-stress-responses-in-normal-and-malignant-cells
#17
REVIEW
Inge M N Wortel, Laurens T van der Meer, Michael S Kilberg, Frank N van Leeuwen
Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells. ATF4 controls the expression of a wide range of adaptive genes that allow cells to endure periods of stress, such as hypoxia or amino acid limitation. However, under persistent stress conditions, ATF4 promotes the induction of apoptosis. Recent advances point to a role for post-translational modifications (PTMs) and epigenetic mechanisms in balancing these pro- and anti-survival effects of ATF4...
August 7, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28797098/comparative-genomics-of-two-super-shedder-isolates-of-escherichia-coli-o157-h7
#18
Robab Katani, Rebecca Cote, Indira T Kudva, Chitrita DebRoy, Terrance M Arthur, Vivek Kapur
Shiga toxin-producing Escherichia coli O157:H7 (O157) are zoonotic foodborne pathogens and of major public health concern that cause considerable intestinal and extra-intestinal illnesses in humans. O157 colonize the recto-anal junction (RAJ) of asymptomatic cattle who shed the bacterium into the environment through fecal matter. A small subset of cattle, termed super-shedders (SS), excrete O157 at a rate (≥ 104 CFU/g of feces) that is several orders of magnitude greater than other colonized cattle and play a major role in the prevalence and transmission of O157...
2017: PloS One
https://www.readbyqxmd.com/read/28797077/gender-difference-in-nash-susceptibility-roles-of-hepatocyte-ikk%C3%AE-and-sult1e1
#19
Noriko Matsushita, Mohamed T Hassanein, Marcos Martinez-Clemente, Raul Lazaro, Samuel W French, Wen Xie, Keane Lai, Michael Karin, Hidekazu Tsukamoto
Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice...
2017: PloS One
https://www.readbyqxmd.com/read/28794505/differential-transcriptome-of-tolerogenic-versus-inflammatory-dendritic-cells-points-to-modulated-t1d-genetic-risk-and-enriched-immune-regulation
#20
T Nikolic, N J C Woittiez, A van der Slik, S Laban, A Joosten, C Gysemans, C Mathieu, J J Zwaginga, B Koeleman, B O Roep
Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD3/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators...
August 10, 2017: Genes and Immunity
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