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Calcineurin

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https://www.readbyqxmd.com/read/28645931/a-potential-role-of-the-unfolded-protein-response-in-post-transplant-cancer
#1
REVIEW
Sandra Bodeau, Chloé Sauzay, Olivier Pluquet, Gabriel Choukroun, Antoine Galmiche
Cancer is one of the major causes of mortality in organ transplant patients receiving immunosuppressive regimen based on Cyclosporin A (CsA). Organ transplantation and chronic immunosuppression are typically associated with skin cancers (both squamous cell carcinoma and melanoma) and renal cell carcinoma (RCC). Recent studies have shown that in addition to its immunosuppressive effects, accounted for by the inhibition of calcineurin and the modulation of the transcriptional programme of lymphocytes, CsA also directly stimulates the growth and aggressive behaviour of various cancer cells...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28642276/dedifferentiation-proliferation-and-redifferentiation-of-adult-mammalian-cardiomyocytes-after-ischemic-injury
#2
Wei Eric Wang, Liangpeng Li, Xuewei Xia, Wenbin Fu, Qiao Liao, Cong Lan, Dezhong Yang, Hongmei Chen, Rongchuan Yue, Cindy S Zeng, Lin Zhou, Bin Zhou, Dayue D Duan, Xiongwen Chen, Steven R Houser, Chunyu Zeng
Background -Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACM) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. Methods -β-actin-GFP transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs...
June 22, 2017: Circulation
https://www.readbyqxmd.com/read/28641881/peripheral-blood-regulatory-t-cell-counts-as-a-predictive-biomarker-for-the-outcome-of-kidney-transplant-a-systematic-review
#3
Francisco Herrera-Gómez, Mónica Vásquez-Seoane, Waldo Del Aguila, Débora Martín-García, Álvaro Maurtua-Briseño Meiggs, Anunciación González-López, Beatriz Andrés-Martín, Álvaro Nava-Rebollo, Fernando Casquero-Fernández, Pilar Pascual-Núñez, Jesús Grande-Villoria, Jesús Bustamante-Bustamante, Carlos Ochoa-Sangrador, Claude Lambert, Alicia Mendiluce-Herrero
BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched...
June 19, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28641548/pediatric-cutaneous-graft-versus-host-disease-a-review
#4
Connie R Shi, Jennifer T Huang, Vinod E Nambudiri
BACKGROUND: Graft versus host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation in the pediatric population. The most common clinical manifestation of GVHD is in the skin. This article will present a review of key concepts related to pediatric cutaneous GVHD, including pathophysiology, clinical epidemiology, diagnosis, and treatment options. GVHD is an immune-mediated process characterized by an inflammatory immune response in acute GVHD and mixed inflammatory and fibrotic states in chronic GVHD...
June 14, 2017: Current Pediatric Reviews
https://www.readbyqxmd.com/read/28640529/effect-of-everolimus-versus-calcineurin-inhibitors-on-quality-of-life-in-heart-transplant-recipients-during-a-3-year-follow-up-results-of-a-randomized-controlled-trial-schedule
#5
A Relbo Authen, I Grov, K Karason, F Gustafsson, H Eiskjaer, G Rådegran, E Gude, K Jansson, G Dellgren, D Solbu, S Arora, A K Andreassen, L Gullestad
The SCHEDULE trial was a 12-month, randomized, open-label, parallel-group trial that compared everolimus (EVR; n=56) to conventional CsA (n=59) immunosuppression. Previously, we reported that EVR outperformed CsA in improving renal function and coronary artery vasculopathy, despite a higher rejection rate with EVR. The present study aimed to compare the effects of these treatments on quality of life (QoL). Within 5 postoperative days, patients (mean age 50±13 years, 27% women) were randomized to EVR or a standard CsA dosage (CsA group)...
June 22, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28640392/calcineurin-inhibitors-exacerbate-coronary-arteritis-via-the-myd88-signaling-pathway-in-a-murine-model-of-kawasaki-disease
#6
Kenji Murata, Yoshitomo Motomura, Tamami Tanaka, Shunsuke Kanno, Takahisa Yano, Mitsuho Onimaru, Atsushi Shimoyama, Hisanori Nishio, Yasunari Sakai, Masatsugu Oh-Hora, Hiromitsu Hara, Koichi Fukase, Hidetoshi Takada, Satohiro Masuda, Shouichi Ohga, Sho Yamasaki, Toshiro Hara
Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (Nod1) in wild-type, SCID, CARD9(-/-) , and MyD88(-/-) mice...
June 22, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28639592/current-status-of-lupus-nephritis
#7
REVIEW
Ajay Jaryal, Sanjay Vikrant
Systemic lupus erythematosus (SLE) is a systemic disease of unknown aetiology with variable course and prognosis. Lupus nephritis (LN) is one of the important disease manifestations of SLE with considerable influence on patient outcomes. Immunosuppression therapy has made it possible to control the disease with improved life expectancy and quality of life. In the last few decades, various studies across the globe have clarified the role, dose and duration of immunosuppression currently in use and also provided evidence for new agents such as mycophenolate mofetil, calcineurin inhibitors and rituximab...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28638997/follistatin-treatment-suppresses-serca1b-levels-independently-of-other-players-of-calcium-homeostasis-in-c2c12-myotubes
#8
János Fodor, Adrienn Gomba-Tóth, Tamás Oláh, János Almássy, Ernő Zádor, László Csernoch
Follistatin (FS) is a high affinity activin-binding protein, neutralizing the effects of the Transforming Growth Factor-beta (TGF-β) superfamily members, as myostatin (MSTN). Since MSTN emerged as a negative regulator, FS has been considered as a stimulator of skeletal muscle growth and differentiation. Here, we studied the effect of FS administration on the Ca(2+)-homeostasis of differentiating C2C12 skeletal muscle cells. FS-treatment increased the fusion index, the size of terminally differentiated myotubes, and transiently elevated the expression of the calcium-dependent protein phosphatase, calcineurin, at the beginning of differentiation...
June 21, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/28631570/the-effect-of-rcan1-on-the-biological-behaviors-of-small-cell-lung-cancer
#9
Ningqiang Ma, Weiwei Shen, Hailin Pang, Ning Zhang, Hong Shi, Jianlin Wang, Helong Zhang
Bone is the third most common site of cancer metastasis. In total, 30%-40% of lung cancer cases can develop skeletal metastasis for which no effective therapy in clinic is available. RCAN1 (regulator of calcineurin 1) is an important regulator in angiogenesis which is vital to tumor growth. In this study, we investigated the changes of biological behaviors in SBC-5 and SBC-3 cells after the RCAN1 expression level was changed. Briefly, overexpression of RCAN1 significantly attenuated their malignancy, including decreased ability of proliferation, colony formation, migration, invasion, and bone adherence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627448/opiate-exposure-state-controls-dopamine-d3-receptor-and-cdk5-calcineurin-signaling-in-the-basolateral-amygdala-during-reward-and-withdrawal-aversion-memory-formation
#10
Laura G Rosen, Walter J Rushlow, Steven R Laviolette
The dopamine (DA) D3 receptor (D3R) is highly expressed in the basolateral nucleus of the amygdala (BLA), a neural region critical for processing opiate-related reward and withdrawal aversion-related memories. Functionally, D3R transmission is linked to downstream Cdk5 and calcineurin signaling, both of which regulate D3R activity states and play critical roles in memory-related synaptic plasticity. Previous evidence links D3R transmission to opiate-related memory processing, however little is known regarding how chronic opiate exposure may alter D3R-dependent memory mechanisms...
June 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28624888/steady-state-pharmacokinetics-of-mycophenolic-acid-in-renal-transplant-patients-exploratory-analysis-of-the-effects-of-cyclosporine-recipients-and-donors-abcc2-gene-variants-and-their-interactions
#11
N Božina, Z Lalić, S Nađ-Škegro, A Borić-Bilušić, T Božina, Ž Kaštelan, V Trkulja
PURPOSE: The study aims to evaluate the impact of recipients' and donors' polymorphisms in multidrug resistance-associated protein 2 (MRP2) gene ABCC2 -24C>T and 1249G>A on disposition of mycophenolic acid (MPA) and their interaction with cyclosporine (CsA) (compared to tacrolimus, TAC) in stable de novo adult renal transplant patients of Croatian origin. METHODS: A total of 68 recipient-donor pairs were genotyped. Steady-state pharmacokinetics of MPA was assessed by the model-independent method...
June 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28624108/modification-of-immunosuppressive-therapy-as-risk-factor-for-complications-after-liver-transplantation
#12
REVIEW
Paolo De Simone, Paola Carrai, Laura Coletti, Davide Ghinolfi, Stefania Petruccelli, Franco Filipponi
Management of complications post-liver transplantation (LT) includes immunosuppressive manipulations with the aim to reduce the overall burden of immunologic suppression and compensate for renal, cardiovascular, metabolic toxicities, and for the increased oncologic risk. Two approaches can be implemented to reduce immunosuppression-related adverse events: upfront schedules tailored to the pretransplant individual patient's risk profile versus downstream modifications in the event of immunosuppression-related complications...
April 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28623616/cyclosporine-a-mediated-il-6-expression-promotes-neural-induction-in-pluripotent-stem-cells
#13
Ashwathnarayan Ashwini, Sushma S Naganur, Bhaskar Smitha, Preethi Sheshadri, Jyothi Prasanna, Anujith Kumar
Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28621638/urologic-complications-after-renal-transplant-a-single-center-experience
#14
Hakan Sözen, Metin Onaran, Onur Özen, Aydın Dalgıç
OBJECTIVES: Urologic complications after kidney transplant are associated with significant morbidity, mortality, and prolonged hospital stay. An intervention or second surgical procedure is frequently required. Here, we report urologic complications in adult kidney recipients. MATERIALS AND METHODS: Since 2006, 171 adult kidney transplant procedures have been performed at the Gazi University Transplantation Center (Ankara, Turkey). Among these patients, there were 65 adult female (38%) and 106 adult male (62%) recipients...
June 16, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#15
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28614711/dapk1-mediates-ltd-by-making-camkii-glun2b-binding-ltp-specific
#16
Dayton J Goodell, Vincent Zaegel, Steven J Coultrap, Johannes W Hell, K Ulrich Bayer
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28611248/the-aspergillus-fumigatus-crza-transcription-factor-activates-chitin-synthase-gene-expression-during-the-caspofungin-paradoxical-effect
#17
Laure Nicolas Annick Ries, Marina Campos Rocha, Patrícia Alves de Castro, Rafael Silva-Rocha, Roberto Nascimento Silva, Fernanda Zanolli Freitas, Leandro José de Assis, Maria Célia Bertolini, Iran Malavazi, Gustavo H Goldman
Aspergillus fumigatus is an opportunistic fungal pathogen that causes invasive aspergillosis (IA), a life-threatening disease in immunocompromised humans. The echinocandin caspofungin, adopted as a second-line therapy in combating IA, is a β-1,3-glucan synthase inhibitor, which, when used in high concentrations, reverts the anticipated A. fumigatus growth inhibition, a phenomenon called the "caspofungin paradoxical effect" (CPE). The CPE has been widely associated with increased chitin content in the cell wall due to a compensatory upregulation of chitin synthase-encoding genes...
June 13, 2017: MBio
https://www.readbyqxmd.com/read/28611128/decreased-kcne2-expression-participates-in-the-development-of-cardiac-hypertrophy-by-regulation-of-calcineurin-nfat-nuclear-factor-of-activated-t-cells-and-mitogen-activated-protein-kinase-pathways
#18
Wenjuan Liu, Jianxin Deng, Wenwen Ding, Gang Wang, Yuanyuan Shen, Junmeng Zheng, Xiaoming Zhang, Yizhi Luo, Chifei Lv, Yonghui Wang, Liqing Chen, Dewen Yan, Ryan L Boudreau, Long-Sheng Song, Jie Liu
BACKGROUND: KCNE2 is a promiscuous auxiliary subunit of voltage-gated cation channels. A recent work demonstrated that KCNE2 regulates L-type Ca(2+) channels. Given the important roles of altered Ca(2+) signaling in structural and functional remodeling in diseased hearts, this study investigated whether KCNE2 participates in the development of pathological hypertrophy. METHODS AND RESULTS: We found that cardiac KCNE2 expression was significantly decreased in phenylephrine-induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes and in transverse aortic constriction-induced cardiac hypertrophy in mice, as well as in dilated cardiomyopathy in human...
June 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28608696/immunomodulatory-activity-of-ganoderma-atrum-polysaccharide-on-purified-t-lymphocytes-through-ca2-can-and-mapk-pathway-based-on-rna-seq
#19
Quan-Dan Xiang, Qiang Yu, Hui Wang, Ming-Ming Zhao, Shi-Yu Liu, Shaoping Nie, Ming-Yong Xie
Our previous study has demonstrated that Ganoderma atrum polysaccharide (PSG-1) has immunomodulatory activity on spleen lymphocytes. However, how PSG-1 exerts its effect on purified lymphocytes is still obscure. Thus, this study aimed to investigate the immunomodulatory activity of PSG-1 on purified T lymphocytes, and further elucidate the underlying mechanism based on RNA-seq. Our results showed that PSG-1 promoted T lymphocytes proliferation and increased the production of IL-2, IFN-γ and IL-12. Meanwhile, RNA-seq analysis found 394 differentially expressed genes...
June 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28608641/risk-factors-for-pneumocystis-pneumonia-after-the-first-6-months-following-renal-transplantation
#20
Emmanuel Faure, Arnaud Lionet, Eric Kipnis, Christian Noël, Marc Hazzan
Pneumocystis pneumonia (PCP) incidence was decreased in renal transplant thanks to prophylaxis, recommended during the first months after transplantation. However, many late PCP cases are observed after the first 6 months and recommendations to maintain or reintroduce prophylaxis are lacking. The objective of the study was to identify risk factors to guide the individual prescription of prophylaxis, 6 months after transplantation. Thirty-three late PCP cases were identified between 1995 and 2012 in Lille Hospital, France, and were compared to 72 randomized controls transplant recipients...
June 13, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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