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https://www.readbyqxmd.com/read/28340347/rejuvenation-by-therapeutic-elimination-of-senescent-cells
#1
Paul Krimpenfort, Anton Berns
In this issue of Cell, Baar et al. show how FOXO4 protects senescent cell viability by keeping p53 sequestered in nuclear bodies, preventing it from inducing apoptosis. Disrupting this interaction with an all-D amino acid peptide (FOXO4-DRI) restores p53's apoptotic role and ameliorates the consequences of senescence-associated loss of tissue homeostasis.
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28334745/disease-correction-by-aav-mediated-gene-therapy-in-a-new-mouse-model-of-mucopolysaccharidosis-type-iiid
#2
Carles Roca, Sandra Motas, Sara Marcó, Albert Ribera, Víctor Sánchez, Xavier Sánchez, Joan Bertolin, Xavier León, Jennifer Pérez, Miguel Garcia, Pilar Villacampa, Jesús Ruberte, Anna Pujol, Virginia Haurigot, Fatima Bosch
Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D...
February 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334696/effects-of-hypergravity-on-the-angiogenic-potential-of-endothelial-cells
#3
Raquel Costa-Almeida, Daniel T O Carvalho, Miguel J S Ferreira, Guilherme Aresta, Manuela E Gomes, Jack J W A van Loon, Kim Van der Heiden, Pedro L Granja
Angiogenesis, the formation of blood vessels from pre-existing ones, is a key event in pathology, including cancer progression, but also in homeostasis and regeneration. As the phenotype of endothelial cells (ECs) is continuously regulated by local biomechanical forces, studying endothelial behaviour in altered gravity might contribute to new insights towards angiogenesis modulation. This study aimed at characterizing EC behaviour after hypergravity exposure (more than 1g), with special focus on cytoskeleton architecture and capillary-like structure formation...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28333829/acute-traumatic-coagulopathy-the-elephant-in-a-room-of-blind-scientists
#4
Michael A Meledeo, Maryanne C Herzig, James A Bynum, Xiaowu Wu, Anand K Ramasubramanian, Daniel N Darlington, Kristin M Reddoch, Andrew P Cap
Acute traumatic coagulopathy (ATC) is the failure of coagulation homeostasis that can rapidly arise following traumatic injury, hemorrhage, and shock; it is associated with higher injury severity, coagulation abnormalities, and increased blood transfusions. ATC has historically been defined by a prolonged prothrombin time (PT), although newer, more informative measurements of hemostatic function have been employed to improve diagnosis and support clinical decision making. The underlying biochemical mechanisms of and best practice therapeutics for ATC remain under active investigation because of its significant correlation to poor outcomes...
March 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28333388/central-regulation-of-glucose-homeostasis
#5
Alexander Tups, Jonas Benzler, Domenico Sergi, Sharon R Ladyman, Lynda M Williams
The ability of the brain to directly control glucose levels in the blood independently of its effects on food intake and body weight has been known ever since 1854 when Claude Bernard, a French physiologist, discovered that lesioning the floor of the fourth ventricle in rabbits led to a rise of sugar in the blood. Despite this outstanding discovery at that time, it took more than 140 years before progress started to be made in identifying the underlying mechanisms of brain-mediated control of glucose homeostasis...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333384/transcriptional-regulation-of-adipogenesis
#6
Paula Mota de Sá, Allison J Richard, Hardy Hang, Jacqueline M Stephens
Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28332708/dual-specificity-tyrosine-phosphorylation-regulated-kinase-2-regulates-osteoclast-fusion-in-a-cell-heterotypic-manner
#7
Gali Guterman-Ram, Milena Pesic, Ayelet Orenbuch, Tal Czeiger, Anastasia Aflalo, Noam Levaot
Monocyte fusion into osteoclasts, bone resorbing cells, plays a key role in bone remodeling and homeostasis; therefore, aberrant cell fusion may be involved in a variety of debilitating bone diseases. Research in the last decade has led to the discovery of genes that regulate osteoclast fusion, but the basic molecular and cellular regulatory mechanisms underlying the fusion process are not completely understood. Here, we reveal a role for Dyrk2 in osteoclast fusion. We demonstrate that Dyrk2 down regulation promotes osteoclast fusion, whereas its overexpression inhibits fusion...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28332615/integrative-variants-haplotypes-and-diplotypes-of-the-capn3-and-frmd5-genes-and-several-environmental-exposures-associate-with-serum-lipid-variables
#8
Tao Guo, Rui-Xing Yin, Ling Pan, Shuo Yang, Liu Miao, Feng Huang
To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332577/absence-of-role-of-dietary-protein-sensing-in-the-metabolic-benefits-of-duodenal-jejunal-bypass-in-the-mouse
#9
Aude Barataud, Daisy Goncalves, Jennifer Vinera, Carine Zitoun, Adeline Duchampt, Amandine Gautier-Stein, Gilles Mithieux
Roux-en-Y gastric bypass (RYGB) induces remission or substantial improvement of type 2 diabetes mellitus (T2D) but underlying mechanisms are still unclear. The beneficial effects of dietary proteins on energy and glucose homeostasis are mediated by the antagonist effects of peptides toward mu-opioid receptors (MORs), which are highly expressed in the distal gut. We hypothesized that the beneficial effects of RYGB could depend at least in part on the interaction of peptides from food with intestinal MORs. Duodenal-jejunal bypass (DJB) was performed in obese and lean wild-type (WT) or MOR deficient (MOR(-/-)) mice...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332200/immunoregulation-of-inflammatory-and-inhibitory-cytokines-by-vitamin-d3-in-patients-with-inflammatory-bowel-diseases-ibd
#10
REVIEW
Hussaini Mohammed Alhassan, Abbas Mirshafiey, Homayoun Vahedi, Gholamreza Hemmasi, Ateke Moussavi Nasl Khameneh, Karim Parastouei, Ali Akbar Saboor-Yaraghi
Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract, caused by an aberrant and exaggerated immunological response in the gut. Supplementation of Vitamin D3 in IBD patients exerts both direct and indirect regulatory roles on the naïve T-cells, thereby maintaining a balance between inflammatory and inhibitory cytokines. The direct actions of Vitamin D3 on naïve T-cells result in the proliferation of more regulatory T-cells and inhibitory cytokines such as IL-4, IL-10, and IL-5...
March 22, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28331855/diabetes-in-hfe-hemochromatosis
#11
REVIEW
James C Barton, Ronald T Acton
Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28331208/metabolic-regulation-of-inflammation
#12
REVIEW
Timo Gaber, Cindy Strehl, Frank Buttgereit
Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions...
March 23, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28330496/calcium-dysregulation-functional-calpainopathy-and-endoplasmic-reticulum-stress-in-sporadic-inclusion-body-myositis
#13
David R Amici, Iago Pinal-Fernandez, Davi A G Mázala, Thomas E Lloyd, Andrea M Corse, Lisa Christopher-Stine, Andrew L Mammen, Eva R Chin
Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca(2+)) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca(2+) dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca(2+) regulation in IBM patients...
March 22, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28327563/health-benefits-and-consequences-of-the-eastern-orthodox-fasting-in-monks-of-mount-athos-a-cross-sectional-study
#14
S N Karras, A Persynaki, A Petróczi, E Barkans, H Mulrooney, M Kypraiou, T Tzotzas, K Tziomalos, K Kotsa, A A Tsioudas, C Pichard, D P Naughton
BACKGROUND/OBJECTIVES: Greek Orthodox fasting (OF), which involves 180-200 days of fasting per year, is dictated by the Christian Orthodox religion. For the first time, this cross-sectional study examines the characteristics and the effects of OF on anthropometry, cardiometabolic markers and calcium homeostasis in Athonian monks (AMs). SUBJECTS/METHODS: Daily intakes of energy, macro- and micronutrients of a day during a weekend of Nativity Fast, defined as non-restrictive day (NRD), and a weekday during Great Lent, labeled as restrictive day (RD) were recorded...
March 22, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28325262/the-roles-of-reactive-oxygen-species-ros-and-autophagy-in-the-survival-and-death-of-leukemia-cells
#15
REVIEW
Yong-Feng Chen, Hao Liu, Xin-Jing Luo, Zhiqiang Zhao, Zhen-You Zou, Jing Li, Xiao-Jing Lin, Yong Liang
As a clonal disease of hematopoietic stem cells (HSCs), the etiology and pathogenesis of leukemia is not fully understood. Recent studies suggest that cellular homeostasis plays an essential role in maintaining the function of HSCs because dysregulation of cellular homeostasis is one of the major factors underlying the malignant transformation of HSCs. Reactive oxygen species (ROS) and autophagy, key factors regulating cellular homeostasis, are commonly observed in the human body. Autophagy can be induced by ROS through a variety of signaling pathways, and conversely inhibits ROS-induced damage to cells and tissues...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28325213/mitochondrion-a-common-organelle-for-distinct-cell-deaths
#16
Z Wang, C Figueiredo-Pereira, C Oudot, H L A Vieira, C Brenner
Mitochondria are deeply involved in cell fate decisions via their multiple roles in metabolism, cell growth, and cell death. In healthy cells, these functions are highly regulated to provide sufficient energy for cell function, maintain cell homeostasis, and avoid undesirable cell death. This is achieved by an orchestrated cooperation of cellular and molecular mechanisms such as mitochondrial mass control (mitophagy vs biogenesis), oxidative phosphorylation, redox and calcium homeostasis, and the balance between pro- and antiapoptotic proteins...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28324069/glucose-homeostasis-regulation-by-peripheral-circadian-clocks-in-rodents-and-humans
#17
Frederic Gachon, Ursula Loizides-Mangold, Volodymyr Petrenko, Charna Dibner
Most organisms, including humans, have developed an intrinsic system of circadian oscillators, allowing the anticipation of events related to the rotation of the Earth around its own axis. The mammalian circadian timing system orchestrates nearly all aspects of physiology and behavior. Together with systemic signals, emanating from the central clock which resides in the hypothalamus, peripheral oscillators orchestrate tissue-specific fluctuations in gene expression, protein synthesis, and posttranslational modifications, driving overt rhythms in physiology and behavior...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#18
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323996/molecular-physiology-of-the-hypocalcemic-action-of-fibroblast-growth-factor-23-in-zebrafish-danio-rerio
#19
Chia-Hao Lin, Huei-Jyun Hu, Pung-Pung Hwang
Fibroblast growth factor 23 (FGF23), a hormone required for phosphorus metabolism, was recently proposed to act on Ca2+ uptake; however, the available evidences of how FGF23 controls the body fluid Ca2+ homeostasis needs to be further clarified. The use of zebrafish as a model system revealed that FGF23 is specifically expressed in the corpuscles of Stannius (CS), an organ involved in Ca2+ homeostasis in fish, and its expression is stimulated by ambient water with a high Ca2+ level. The overexpression of FGF23 inhibited Ca2+ uptake by downregulating the mRNA expression of epithelium calcium channel (ECaC)...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323977/short-term-vs-long-term-effects-of-adipocyte-toll-like-receptor-4-activation-on-insulin-resistance-in-male-mice
#20
Caroline Tao, William L Holland, Qiong A Wang, Mengle Shao, Lin Jia, Kai Sun, Xiaoli Lin, Yi-Chun Kuo, Joshua A Johnson, Ruth Gordillo, Joel K Elmquist, Philipp E Scherer
Chronic exposure to diets high in saturated fat (HFD) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance. A possible mediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocyte-specific deletion of TLR4, the "TADIPO mouse". Consistent with a critical role for inflammation as a positive force for healthy adipose tissue expansion, chronic HFD exposure resulted in exacerbated whole body and muscle insulin resistance in the absence of TLR4 in the adipocyte...
February 24, 2017: Endocrinology
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