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Calcineurin

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https://www.readbyqxmd.com/read/28748621/outcomes-of-matched-sibling-donor-bone-marrow-transplantation-in-children-using-single-agent-calcineurin-inhibitors-as-prophylaxis-for-graft-versus-host-disease
#1
Caitlin W Elgarten, Danielle E Arnold, Nancy J Bunin, Alix E Seif
BACKGROUND: Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years...
July 27, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28746924/cyclin-dependent-kinase-inhibitor-p21waf1-cip1-facilitates-the-development-of-cardiac-hypertrophy
#2
Yang-Fei Tong, Yan Wang, Yuan-Yuan Ding, Jing-Mei Li, Xi-Chun Pan, Xiao-Lan Lu, Xiao-Hong Chen, Ya Liu, Hai-Gang Zhang
BACKGROUND/AIMS: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. METHODS: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28743539/recommendations-of-everolimus-use-in-liver-transplant
#3
Angel Rubín Suárez, Itxarone Bilbao Aguirre, Javier Fernández-Castroagudin, José Antonio Pons Miñano, Magdalena Salcedo Plaza, Evaristo Varo Pérez, Martín Prieto Castillo
Mammalian target of rapamycin (mTOR) inhibitors, everolimus (EVL) and sirolimus are immunosuppressive agents with a minor nephrotoxic effect, limited to the development of proteinuria in some cases. The combination of EVL and low-dose tacrolimus has proven to be as safe and effective as standard therapy with tacrolimus for the prevention of acute cellular rejection. Early initiation of EVL-based immunosuppressive regimens with reduced exposure to calcineurin inhibitors has been shown to significantly improve renal function of LT recipients during induction and maintenance phases, with comparable efficacy and safety profiles...
July 22, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28742147/genetic-analysis-of-the-regulation-of-the-voltage-gated-calcium-channel-homolog-cch1-by-the-%C3%AE-subunit-homolog-ecm7-and-cortical-er-protein-scs2-in-yeast
#4
Takafumi Kato, Aya Kubo, Tatsuya Nagayama, Shinichiro Kume, Chikara Tanaka, Yoshitaka Nakayama, Kazuko Iida, Hidetoshi Iida
The yeast Cch1/Mid1 Ca2+ channel is equivalent to animal voltage-gated Ca2+ channels and activated in cells incubated in low Ca2+ medium. We herein investigated the third subunit, Ecm7, under the same cell culture conditions. The deletion of ECM7 slightly lowered Ca2+ influx activity in the CNB1+ background, in which calcineurin potentially dephosphorylates Cch1, but markedly lowered this activity in the cnb1Δ background. The deletion of the C-terminal cytoplasmic region of Ecm7 also reduced Ca2+ influx activity...
2017: PloS One
https://www.readbyqxmd.com/read/28740511/safety-and-tolerance-of-donor-derived-mesenchymal-stem-cells-in-pediatric-living-donor-liver-transplantation-the-mystep1-study
#5
Steffen Hartleif, Michael Schumm, Michaela Döring, Markus Mezger, Peter Lang, Marc H Dahlke, Joachim Riethmüller, Alfred Königsrainer, Rupert Handgretinger, Silvio Nadalin, Ekkehard Sturm
BACKGROUND: Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28736570/genome-wide-identification-and-functional-analysis-of-the-calcineurin-b-like-protein-and-calcineurin-b-like-protein-interacting-protein-kinase-gene-families-in-turnip-brassica-rapa-var-rapa
#6
Xin Yin, Qiuli Wang, Qian Chen, Nan Xiang, Yunqiang Yang, Yongping Yang
The calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complex has been identified as a primary component in calcium sensors that perceives various stress signals. Turnip (Brassica rapa var. rapa) has been widely cultivated in the Qinghai-Tibet Plateau for a century as a food crop of worldwide economic significance. These CBL-CIPK complexes have been demonstrated to play crucial roles in plant response to various environmental stresses. However, no report is available on the genome-wide characterization of these two gene families in turnip...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28736568/bdcipk31-a-calcineurin-b-like-protein-interacting-protein-kinase-regulates-plant-response-to-drought-and-salt-stress
#7
Qingchen Luo, Qiuhui Wei, Ruibin Wang, Yang Zhang, Fan Zhang, Yuan He, Shiyi Zhou, Jialu Feng, Guangxiao Yang, Guangyuan He
Calcineurin B-like protein interacting protein kinases (CIPKs) are vital elements in plant abiotic stress signaling pathways. However, the functional mechanism of CIPKs has not been understood clearly, especially in Brachypodium distachyon, a new monocot model plant. In this study, BdCIPK31, a CIPK gene from B. distachyon was characterized. BdCIPK31 was downregulated by polyethylene glycol, NaCl, H2O2, and abscisic acid (ABA) treatments. Transgenic tobacco plants overexpressing BdCIPK31 presented improved drought and salt tolerance, and displayed hypersensitive response to exogenous ABA...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28730648/calcineurin-inhibitor-withdrawal-or-tapering-for-kidney-transplant-recipients
#8
REVIEW
Krishna M Karpe, Girish S Talaulikar, Giles D Walters
BACKGROUND: Calcineurin inhibitors (CNI) can reduce acute transplant rejection and immediate graft loss but are associated with significant adverse effects such as hypertension and nephrotoxicity which may contribute to chronic rejection. CNI toxicity has led to numerous studies investigating CNI withdrawal and tapering strategies. Despite this, uncertainty remains about minimisation or withdrawal of CNI. OBJECTIVES: This review aimed to look at the benefits and harms of CNI tapering or withdrawal in terms of graft function and loss, incidence of acute rejection episodes, treatment-related side effects (hypertension, hyperlipidaemia) and death...
July 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28730617/methotrexate-for-severe-childhood-atopic-dermatitis-clinical-experience-in-a-tertiary-center
#9
Veronika Dvorakova, Grainne M O'Regan, Alan D Irvine
BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) affects up to 20% of children. Although the majority of patients are adequately controlled using emollients, topical corticosteroids, topical calcineurin inhibitors, or phototherapy, children with moderate to severe AD may require systemic treatment for control. The objective of the current study was to evaluate the efficacy and safety of methotrexate in children with severe AD attending a tertiary referral center. METHODS: A retrospective chart review was undertaken of all children who received methotrexate for severe AD at our tertiary referral center from November 2010 to August 2015...
July 21, 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28729555/inhibition-of-phosphodiesterase-5-suppresses-calcineurin-nfat-mediated-trpc6-expression-in-pulmonary-artery-smooth-muscle-cells
#10
Shaojun Li, Yilin Pan, Rui Ke, Xinming Xie, Cui Zhai, Wenhua Shi, Jian Wang, Xin Yan, Limin Chai, Qingting Wang, Qianqian Zhang, Xiaofan Su, Lan Yang, Li Gao, Manxiang Li
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728400/studies-on-meat-color-myoglobin-content-enzyme-activities-and-genes-associated-with-oxidative-potential-of-pigs-slaughtered-at-different-growth-stages
#11
Qin Ping Yu, Ding Yuan Feng, Juan Xiao, Fan Wu, Xiao Jun He, Min Hao Xia, Tao Dong, Yi Hua Liu, Hui Ze Tan, Shi Geng Zou, Tao Zheng, Xian Hua Ou, Jian Jun Zuo
Objective: This experiment was conducted to investigate meat color, myoglobin (Mb) content, enzyme activities, and expression of genes associated with oxidative potential of pigs slaughtered at different growth stages. Methods: Sixty 4-week-old Duroc × Landrace × Yorkshire pigs were assigned to 6 replicate groups, each containing 10 pigs. One pig from each group was sacrificed at day 35, 63, 98, and 161 to isolate longissimus dorsi and triceps muscles. Results: Meat color scores were higher in pigs at 35 d than those at 63 d and 98 d (P < 0...
May 14, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28724911/honokiol-inhibits-c-met-ho-1-tumor-promoting-pathway-and-its-cross-talk-with-calcineurin-inhibitor-mediated-renal-cancer-growth
#12
Murugabaskar Balan, Samik Chakraborty, Evelyn Flynn, David Zurakowski, Soumitro Pal
Honokiol (HNK) is a small molecule with potent anti-inflammatory and anti-tumorigenic properties; yet the molecular targets of HNK are not well studied. Hyperactivation of the receptor tyrosine kinase c-Met and overexpression of the cytoprotective enzyme heme oxygenase-1 (HO-1) play a critical role in the growth and progression of renal cell carcinoma (RCC). Interestingly, the calcineurin inhibitor (CNI) cyclosporine A (CsA), an immunosuppressant used to prevent allograft rejection, can also increase the risk of RCC in transplant patients...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724617/human-venous-valve-disease-caused-by-mutations-in-foxc2-and-gjc2
#13
Oliver Lyons, Prakash Saha, Christopher Seet, Adam Kuchta, Andrew Arnold, Steven Grover, Victoria Rashbrook, Amélie Sabine, Gema Vizcay-Barrena, Ash Patel, Francesca Ludwinski, Soundrie Padayachee, Tsutomu Kume, Brenda R Kwak, Glen Brice, Sahar Mansour, Pia Ostergaard, Peter Mortimer, Steve Jeffery, Nigel Brown, Taija Makinen, Tatiana V Petrova, Bijan Modarai, Alberto Smith
Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events...
July 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28724396/pathogenic-roles-of-cxcl10-signaling-through-cxcr3-and-tlr4-in-macrophages-and-t-cells-relevance-for-arthritis
#14
Jong-Ho Lee, Bongjun Kim, Won Jong Jin, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone and cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in joint inflammation and bone destruction in arthritis. However, the specific mechanisms by which CXCL10 regulates the recruitment of inflammatory cells and the production of osteoclastogenic cytokines in RA progression are not fully understood...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28720890/iron-overload-exacerbates-age-associated-cardiac-hypertrophy-in-a-mouse-model-of-hemochromatosis
#15
Abitha Sukumaran, JuOae Chang, Murui Han, Shrutika Mintri, Ban-An Khaw, Jonghan Kim
Cardiac damage associated with iron overload is the most common cause of morbidity and mortality in patients with hereditary hemochromatosis, but the precise mechanisms leading to disease progression are largely unexplored. Here we investigated the effects of iron overload and age on cardiac hypertrophy using 1-, 5- and 12-month old Hfe-deficient mice, an animal model of hemochromatosis in humans. Cardiac iron levels increased progressively with age, which was exacerbated in Hfe-deficient mice. The heart/body weight ratios were greater in Hfe-deficient mice at 5- and 12-month old, compared with their age-matched wild-type controls...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28719054/evolutionary-cell-biology-of-proteins-from-protists-to-humans-and-plants
#16
REVIEW
Helmut Plattner
During evolution, the cell as a fine-tuned machine had to undergo permanent adjustments to match changes in its environment, while "closed for repair work" was not possible. Evolution from protists (protozoa and unicellular algae) to multicellular organisms may have occurred in basically two lineages, Unikonta and Bikonta, culminating in mammals and angiosperms (flowering plants), respectively. Unicellular models for unikont evolution are myxamoebae (Dictyostelium) and increasingly also choanoflagellates, whereas, for bikonts, ciliates are preferred models...
July 18, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28717008/the-cardiac-z-disc-protein-cefip-regulates-cardiomyocyte-hypertrophy-by-modulating-calcineurin-signaling
#17
Franziska Dierck, Christian Kuhn, Claudia Rohr, Susanne Hille, Julia Braune, Samuel Sossalla, Sibylle Molt, Peter F M van der Ven, Dieter O Fürst, Norbert Frey
The z-disc is a structural component at the lateral borders of the sarcomere and is important for mechanical stability and contractility of both cardiac and skeletal muscles. Of note, the sarcomeric z-disc also represents a nodal point in cardiomyocyte function and signaling. Mutations of numerous z-disc proteins are associated with cardiomyopathies and muscle diseases. To identify additional z-disc proteins that might contribute to cardiac disease, we employed an in silico screen for cardiac-enriched cDNAs...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28714558/everolimus-and-reduced-calcineurin-inhibitor-therapy-in-pediatric-liver-transplant-recipients-results-from-a-multicenter-prospective-study
#18
Rainer Ganschow, Bo-Goran Ericzon, Anil Dhawan, Khalid Sharif, El-Djouher Martzloff, Barbara Rauer, Jennifer Ng, Patricia Lopez
In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation...
July 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#19
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28712932/pyrrolidine-dithiocarbamate-pdtc-inhibits-inflammatory-signaling-via-expression-of-regulator-of-calcineurin-activity-1-rcan1
#20
Eun Hye Lee, Seon Sook Kim, Su Ryeon Seo
Pyrrolidine dithiocarbamate (PDTC) is a thiol compound that elicits anti-inflammatory effects by inhibiting NF-κB signaling. In this study, we report that regulator of calcineurin activity 1 (RCAN1) expression is induced by PDTC treatment and that increased RCAN1 expression is dependent on the generation of reactive oxygen species (ROS) and activation of p38 MAPK and JNK signaling. We also report that the ability of PDTC to induce RCAN1 is mediated by activator protein-1 (AP-1)-dependent gene transcription, and identified a functional AP-1 binding site in the RCAN1 promoter by producing mutations and conducting chromatin immunoprecipitation (ChIP) analyses...
July 13, 2017: Biochemical Pharmacology
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