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Paracrine effect

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https://www.readbyqxmd.com/read/28734988/can-adverse-effects-of-excessive-vitamin-d-supplementation-occur-without-developing-hypervitaminosis-d
#1
REVIEW
Mohammed S Razzaque
Vitamin D is a fat-soluble hormone that has endocrine, paracrine and autocrine functions. Consumption of vitamin D-supplemented food & drugs have increased significantly in the last couple of decades due to campaign and awareness programs. Despite such wide use of artificial vitamin D supplements, serum levels of 25 hydroxyvitamin D [25(OH)D] does not always reflect the amount of uptake. In contrast to the safe sunlight exposure, prolonged and disproportionate consumption of vitamin D supplements may lead to vitamin D intoxication, even without developing hypervitaminosis D...
July 19, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28733145/adipocytes-promote-nicotine-induced-injury-of-endothelial-cells-via-the-nf-%C3%AE%C2%BAb-pathway
#2
Xiu Liu, Chao-Nan Wang, Chen-Yang Qiu, Wei Song, Lin-Fang Wang, Bao Liu
Cigarette smoking is one of the most important risk factors of atherosclerosis, which can induce endothelial injury. Meanwhile, adipocytes are the main cell type of perivascular adipose tissue (PVAT), the largest endocrine and paracrine organ and direct anatomical connection to adventitia, which may play a key role in the injury of endothelial cells. We used nicotine to induce dysfunctional HUVECs and adipocytes. In addition, we used a novel model to co-culture HUVECs and adipocytes in vitro by the transwell co-culture system to determine the effect of adipocytes on endothelial injury...
July 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28731853/hormonal-factors-in-the-control-of-the-browning-of-white-adipose-tissue
#3
REVIEW
Jiamiao Hu, Mark Christian
Adipose tissue has been historically classified into anabolic white adipose tissue (WAT) and catabolic brown adipose tissue (BAT). Recent studies have revealed the plasticity of WAT, where white adipocytes can be induced into 'brown-like' heat-producing adipocytes (BRITE or beige adipocytes). Recruiting and activating BRITE adipocytes in WAT (so-called 'browning') is believed to provide new avenues for the treatment of obesity-related diseases. A number of hormonal factors have been found to regulate BRITE adipose development and activity through autocrine, paracrine and systemic mechanisms...
July 21, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28731525/differences-in-stem-cell-processing-lead-to-distinct-secretomes-secretion-implications-for-differential-results-of-previous-clinical-trials-of-stem-cell-therapy-for-myocardial-infarction
#4
Bernhard Wernly, Inês Gonçalves, Attila Kiss, Vera Paar, Tobias Mösenlechner, Michael Leisch, David Santer, Lucas Motloch, Klaus Ulrich Klein, Eva Verena Tretter, Daniel Kretzschmar, Bruno Podesser, Christian Jung, Uta C Hoppe, Michael Lichtenauer
INTRODUCTION: Stem cell therapy for acute myocardial infarction (AMI) seemed to be a promising therapy, however large clinical trials brought differential outcome. It has been shown that paracrine effects of secretomes of stem cells rather than cell therapy might play a fundamental role. The present study sought to compare cell processing protocols of clinical trials and investigated effects of differential cell culture conditions on chemokine secretion and functional effects. METHODS: Different secretomes were compared regarding IL-8, VEGF, MCP-1 and TNF-alpha secretion...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28729401/jak1-stat3-activation-through-a-proinflammatory-cytokine-pathway-leads-to-resistance-to-molecularly-targeted-therapy-in-non-small-cell-lung-cancer
#5
Kazuhiko Shien, Vassiliki A Papadimitrakopoulou, Dennis Ruder, Carmen Behrens, Li Shen, Neda Kalhor, Juhee Song, J Jack Lee, Jing Wang, Ximing Tang, Roy S Herbst, Shinichi Toyooka, Luc Girard, John D Minna, Jonathan M Kurie, Ignacio I Wistuba, Julie G Izzo
Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine interleukin-6 (IL6) and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAFs)...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28726773/t-cell-autonomous-death-induced-by-regeneration-of-inert-glucocorticoid-metabolites
#6
Lourdes Rocamora-Reverte, Holger M Reichardt, Andreas Villunger, GJan Wiegers
Glucocorticoids (GC) are essential regulators of T-cell development and function. Activation of the immune system increases systemic adrenal-derived GC levels which downregulate immune activity as part of a negative feedback control system. Increasing evidence shows, however, that GC can also be derived from extra-adrenal sources such as the thymus or intestine, thus providing local control of GC-mediated effects. The thymus reportedly produces GC, but whether thymic epithelial cells or thymocytes produce GC acting either in an autocrine or paracrine fashion is not clear...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28725488/generation-and-analysis-of-spheroids-from-human-primary-skin-myofibroblasts-an-experimental-system-to-study-myofibroblasts-deactivation
#7
Giuseppina Granato, Maria R Ruocco, Antonino Iaccarino, Stefania Masone, Gaetano Calì, Angelica Avagliano, Valentina Russo, Claudio Bellevicine, Gaetano Di Spigna, Giuseppe Fiume, Stefania Montagnani, Alessandro Arcucci
Myofibroblasts are activated fibroblasts involved in tissue repair and cancer. They are characterized by de novo expression of α-smooth muscle actin (α-SMA), immunoregulatory phenotype and paracrine interaction with normal and tumorigenic cells leading to cell proliferation. At the end of wound-healing myofibroblasts undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also subjected to a programmed necrosis-like cell death, termed nemosis, associated with cyclooxygenase-2 (COX-2) expression induction and inflammatory response...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#8
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28721155/clinical-importance-of-epicardial-adipose-tissue
#9
Eszter Nagy, Adam L Jermendy, Bela Merkely, Pal Maurovich-Horvat
Different visceral fat compartments have several systemic effects and may play a role in the development of both insulin resistance and cardiovascular diseases. In the last couple of years special attention has been paid to the epicardial adipose tissue (EAT), which can be quantified by non-invasive cardiac imaging techniques. The epicardial fat is a unique fat compartment between the myocardium and the visceral pericardium sharing a common embryologic origin with the visceral fat depot. Epicardial adipose tissue has several specific roles, and its local effects on cardiac function are incorporated in the complex pathomechanism of coronary artery disease...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28720779/mimicking-paracrine-tgf%C3%AE-1-signals-during-myofibroblast-differentiation-in-3d-collagen-networks
#10
Michael Ansorge, Jiranuwat Sapudom, Marina Chkolnikov, Martin Wilde, Ulf Anderegg, Stephanie Möller, Matthias Schnabelrauch, Tilo Pompe
TGFβ1 is a key regulator for induction of tissue remodeling after dermal wounding. We present a model of paracrine delivery of TGFβ1 for differentiation of dermal fibroblasts based on a fibrillar 3D collagen matrix and embedded TGFβ1 releasing microparticles. We found differentiation into myofibroblasts was achieved in a TGFβ1 dependent manner at much lower doses than systemic delivery. This effect is accounted to the slow and sustained TGFβ1 release mimicking paracrine cell signals.
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#11
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28713437/astragalus-extract-mixture-ht042-increases-longitudinal-bone-growth-rate-by-upregulating-circulatory-igf-1-in-rats
#12
Donghun Lee, Sung Hyun Lee, Yoon Hee Lee, Jungbin Song, Hocheol Kim
Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of "height growth of children." HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28708509/gdf8-activates-p38-mapk-signaling-during-porcine-oocyte-maturation-in%C3%A2-vitro
#13
Junchul David Yoon, Seon-Ung Hwang, Eunhye Kim, Minghui Jin, Soochong Kim, Sang-Hwan Hyun
Growth Differentiation Factor 8 (GDF8) is a member of the transforming growth factor-β (TGF-β) family and has been identified as a strong physiological regulator. This factor is expressed as a paracrine factor in mural granulosa cells. To investigate the effects of GDF8 on the in vitro maturation (IVM) of porcine oocytes, we assessed the quality of matured oocytes as well as the specific gene transcription and protein activation levels in oocytes and cumulus cells (CCs) after IVM and subsequent embryonic development after in vitro fertilization (IVF) and parthenogenetic activation (PA)...
June 6, 2017: Theriogenology
https://www.readbyqxmd.com/read/28705795/selective-deletion-of-leptin-signaling-in-endothelial-cells-enhances-neointima-formation-and-phenocopies-the-vascular-effects-of-diet-induced-obesity-in-mice
#14
Astrid Hubert, Magdalena L Bochenek, Eva Schütz, Rajinikanth Gogiraju, Thomas Münzel, Katrin Schäfer
OBJECTIVE: Obesity is associated with elevated circulating leptin levels and hypothalamic leptin resistance. Leptin receptors (LepRs) are expressed on endothelial cells, and leptin promotes neointima formation in a receptor-dependent manner. Our aim was to examine the importance of endothelial LepR (End.LepR) signaling during vascular remodeling and to determine whether the cardiovascular consequences of obesity are because of hyperleptinemia or endothelial leptin resistance. APPROACH AND RESULTS: Mice with loxP-flanked LepR alleles were mated with mice expressing Cre recombinase controlled by the inducible endothelial receptor tyrosine kinase promoter...
July 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28703802/an-autocrine-inflammatory-forward-feedback-loop-after-chemotherapy-withdrawal-facilitates-the-repopulation-of-drug-resistant-breast-cancer-cells
#15
Deyong Jia, Li Li, Sulaiman Andrew, David Allan, Xuguang Li, Jonathan Lee, Guang Ji, Zemin Yao, Suresh Gadde, Danial Figeys, Lisheng Wang
Stromal cells, infiltrating immune cells, paracrine factors and extracellular matrix have been extensively studied in cancers. However, autocrine factors produced by tumor cells and communications between autocrine factors and intracellular signaling pathways in the development of drug resistance, cancer stem-like cells (CSCs) and tumorigenesis have not been well investigated, and the precise mechanism and tangible approaches remain elusive. Here we reveal a new mechanism by which cytokines produced by breast cancer cells after chemotherapy withdrawal activate both Wnt/β-catenin and NF-κB pathways, which in turn further promote breast cancer cells to produce and secrete cytokines, forming an autocrine inflammatory forward-feedback loop to facilitate the enrichment of drug-resistant breast cancer cells and/or CSCs...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#16
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28701866/inhibitory-effects-of-ginsenosides-on-basic-fibroblast-growth-factor-induced-melanocyte-proliferation
#17
Ji Eun Lee, Jong Il Park, Cheol Hwan Myung, Jae Sung Hwang
BACKGROUND: UV-B-exposed keratinocytes secrete various paracrine factors. Among these factors, basic fibroblast growth factor (bFGF) stimulates the proliferation of melanocytes. Ginsenosides, the major active compounds of ginseng, are known to have broad pharmacological effects. In this study, we examined the antiproliferative effects of ginsenosides on bFGF-induced melanocyte proliferation. METHODS: We investigated the inhibitory effects of Korean Red Ginseng and ginsenosides from Panax ginseng on bFGF-induced proliferation of melan-a melanocytes...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28701474/detecting-human-coronary-inflammation-by-imaging-perivascular-fat
#18
Alexios S Antonopoulos, Fabio Sanna, Nikant Sabharwal, Sheena Thomas, Evangelos K Oikonomou, Laura Herdman, Marios Margaritis, Cheerag Shirodaria, Anna-Maria Kampoli, Ioannis Akoumianakis, Mario Petrou, Rana Sayeed, George Krasopoulos, Constantinos Psarros, Patricia Ciccone, Carl M Brophy, Janet Digby, Andrew Kelion, Raman Uberoi, Suzan Anthony, Nikolaos Alexopoulos, Dimitris Tousoulis, Stephan Achenbach, Stefan Neubauer, Keith M Channon, Charalambos Antoniades
Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo...
July 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28700093/interleukin-10-release-from-astrocytes-suppresses-neuronal-apoptosis-via-the-tlr2-nf%C3%AE%C2%BAb-pathway-in-a-neonatal-rat-model-of-hypoxic-ischemic-brain-damage
#19
Mu Lan He, Ze Yu Lv, Xia Shi, Ting Yang, Yun Zhang, Ting-Yu Li, Jie Chen
The biological function of Interleukin-10 (IL-10) and the relationship between IL-10 secretion and the Toll-like receptor 2 (TLR2) expression levels in the central nervous system following hypoxic-ischemic brain damage (HIBD) are poorly understood. Here, we intend to elucidate the biological function and mechanism of IL-10 secretion following HIBD. In the current study, we used a neonatal rat model of HIBD and found that rats injected with adeno-associated virus (AAV)-IL-10-shRNA (short hairpin RNA) exhibited partially impaired learning and memory function compared to rats administered AAV-control-shRNA...
July 12, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28698554/chondroprotection-by-urocortin-involves-blockade-of-the-mechanosensitive-ion-channel-piezo1
#20
K M Lawrence, R C Jones, T R Jackson, R L Baylie, B Abbott, B Bruhn-Olszewska, T N Board, I C Locke, S M Richardson, P A Townsend
Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3...
July 11, 2017: Scientific Reports
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