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Calcineurin

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https://www.readbyqxmd.com/read/29158264/azole-resistance-in-a-candida-albicans-mutant-lacking-the-abc-transporter-cdr6-roa1-depends-on-tor-signaling
#1
Nitesh Kumar Khandelwal, Neeraj Chauhan, Parijat Sarkar, Brooke D Esquivel, Paola Coccetti, Ashutosh Singh, Alix T Coste, Meghna Gupta, Dominique Sanglard, Theodore C White, Murielle Chauvel, Christophe dEnfert, Amitabha Chattopadhyay, Naseem A Gaur, Alok Kumar Mondal, Rajendra Prasad
ATP-binding cassette (ABC) transporters help export various substrates across the cell membrane and significantly contribute to drug resistance. However, a recent study reported an unusual case in which the loss of an ABC transporter in Candida albicans, orf19.4531 (previously named ROA1), increases resistance against antifungal azoles, which was attributed to an altered membrane potential in the mutant strain. To get further mechanistic insights into this phenomenon, here we confirmed that the plasma membrane localized transporter (renamed CDR6/ROA1 for consistency with C...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29158107/a-functional-role-for-the-epigenetic-regulator-ing1-in-activity-induced-gene-expression-in-primary-cortical-neurons
#2
Laura J Leighton, Qiongyi Zhao, Xiang Li, Chuanyang Dai, Paul R Marshall, Sha Liu, Yi Wang, Esmi L Zajaczkowski, Nitin Khandelwal, Arvind Kumar, Timothy W Bredy, Wei Wei
Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of Inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin, Ppp3r1...
November 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/29157988/de-novo-thrombotic-microangiopathy-after-kidney-transplantation
#3
REVIEW
Neetika Garg, Helmut G Rennke, Martha Pavlakis, Kambiz Zandi-Nejad
Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS...
November 4, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/29157984/ropivacaine-relieves-pain-and-prevents-chondrocyte-degradation-probably-through-calcineurin-nfat1-signaling-pathway-in-osteoarthritis-rats
#4
Wenyu Yao, Qian Han, Lei Wang, Zhiqiang Niu
Calcineurin/NFAT1 signaling pathway plays critical roles in maintaining the homeostasis of articular chondrocytes and in regulating the pathogenesis of osteoarthritis (OA). A few studies demonstrate therapeutic values of ropivacaine (Rop) in OA, but the underlying mechanisms have not been defined. Here, we determined whether Calcineurin/NFAT1 signaling pathway mediates the benefits of Rop to OA. OA rat models were established by a single intra-articular injection of monosodium iodoacetate. The pathophysiology of OA was evaluated by measuring hyperalgesia behavior and the expression of NFAT1, calcineurin, catabolic enzymes in chondrocytes, and chondrogenic markers in affected articular cartilage and primary chondrocyte cultures treated with IL-1β...
November 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29156491/long-term-calcineurin-inhibitor-therapy-and-brain-function-in-patients-after-liver-transplantation
#5
Henning Pflugrad, Anna-Kristina Schrader, Anita Blanka Tryc, Xiaoqi Ding, Heinrich Lanfermann, Elmar Jäckel, Harald Schrem, Jan Beneke, Hannelore Barg-Hock, Jürgen Klempnauer, Karin Weissenborn
BACKGROUND AND AIMS: Calcineurin inhibitors (CNI) frequently induce neurological complications early after orthotopic liver transplantation (OLT). We hypothesize that long-term CNI therapy after OLT causes dose-dependent cognitive dysfunction and alteration of brain structure. METHODS: Eighty-five OLT patients (20 with CNI free, 35 with CNI low dose and 30 with standard dose CNI immunosuppression) underwent psychometric testing and cerebral magnetic resonance tomography about 10 years after OLT to assess brain function and structural brain alterations...
November 20, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29155318/kidney-pathology-after-hematologic-cell-transplantation-a-single-center-observation-study-of-indication-biopsies-and-autopsies
#6
Michael Girsberger, Jörg P Halter, Helmut Hopfer, Michael Dickenmann, Thomas Menter
Hematopoietic cell transplantation (HCT) is an increasingly used treatment for hematologic malignancies as well as for non-malignant diseases. Kidney impairment remains an important early and late posttransplant complication. Numerous histopathologic changes have been reported but the pathophysiology is still incompletely understood. Furthermore, correlations between clinical findings and morphologic changes are not well studied. Between 2000 and 2016, 17 patients after allogeneic (n=12) or autologous (n=5) HCT underwent kidney biopsy for either proteinuria or deterioration of kidney function at our center...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29155316/influence-of-age-on-acute-and-chronic-gvhd-in-children-receiving-hla-identical-sibling-bmt-for-acute-leukemia-implications-for-prophylaxis
#7
Muna Qayed, Tao Wang, Michael T Hemmer, Stephen Spellman, Mukta Arora, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Mahmoud Aljuf, Mouhab Ayas, Menachem Bitan, Mitchell Cairo, Sung Won Choi, Christopher Dandoy, David Delgado, Robert Peter Gale, Gregory Hale, Haydar Frangoul, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Leslie Lehman, John Levine, Margaret MacMillan, David I Marks, Taiga Nishihori, Richard F Olsson, Peiman Hematti, Olov Ringden, Ayman Saad, Prakash Satwani, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Shalini Shenoy, Edmund K Waller, Lolie Yu, Mary M Horowitz, John Horan
Relapse remains the major cause of mortality post hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research suggests that reducing the intensity of calcineurin inhibitor based graft versus host disease (GVHD) prophylaxis may be an effective strategy in abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29151264/renal-protection-strategies-after-heart-transplantation
#8
REVIEW
Daniel Reichart, Hermann Reichenspurner, Markus Johannes Barten
Renal dysfunction caused by calcineurin inhibitor (CNI) nephrotoxicity occurs often and contributes significantly to late mortality after heart transplantation (HTx). Over the last decades, this has prompted many clinical studies in an effort to develop kidney-protecting immunosuppressive strategies including delayed CNI start, minimization, withdrawal or even de-novo CNI avoidance. In the past, these strategies often failed due to the lack of efficacy. Since 2009, novel CNI-reducing strategies are under investigation...
November 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29149976/clinical-challenges-of-tacrolimus-for-maintenance-immunosuppression-post-lung-transplantation
#9
S Ivulich, M Dooley, C Kirkpatrick, G Snell
Lung transplantation (LTx) is a successful treatment option for end-stage lung disease, and immunosuppressant regimens, utilized to prevent rejection of the transplanted graft, are paramount to maintaining long-term graft survival. Immunosuppression can be classified as induction, maintenance, and antirejection therapy. This article focuses on maintenance immunosuppression that includes a combination of a calcineurin inhibitor (CNI), cell cycle inhibitor, and corticosteroid. CNIs remain the cornerstone of immunosuppression following LTx, and tacrolimus is now the preferred CNI, based on a better adverse effect profile and some limited evidence for enhanced efficacy...
November 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29146214/-treatments-of-steroid-dependent-nephrotic-syndrome-in-children
#10
A Couderc, E Bérard, V Guigonis, I Vrillon, J Hogan, V Audard, V Baudouin, C Dossier, O Boyer
Primary nephrotic syndrome (NS) is the most common glomerular disease in children. It is characterized by massive proteinuria and hypoalbuminemia. It typically has a sudden onset and more than 70% of patients will experience at least one relapse. An immunological origin has long been postulated, although the precise molecular mechanisms underlying the disease remain debated. Steroids are the first-line therapy with cumulative dose and duration of initial treatment varying among countries. Steroid-sparing agents may be indicated in case of steroid-dependency or frequent relapses...
November 13, 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29144179/effects-of-active-immunization-against-akirin2-on-muscle-fiber-type-composition-in-pigs
#11
Xiaoling Chen, Yafei Guo, Gang Jia, Hua Zhao, Guangmang Liu, Zhiqing Huang
The objective of this study was to investigate effects of active immunization against Akirin2 on muscle fiber-type composition in pigs. Here we showed that the titer of Akirin2 antibody in pigs immunized with porcine Akirin2 (pAkirin2) was significantly increased. Active immunization against pAkirin2 decreased succinic dehydrogenase and malate dehydrogenase activities and increased lactate dehydrogenase activity in the longissimus dorsi muscle of pigs. Active immunization against pAkirin2 significantly decreased MyHC I and MyHC IIa mRNA expressions and MyHC I protein expression and increased mRNA expressions of MyHC IIb as well as protein expressions of MyHC IIb and fast-MyHC...
November 16, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/29143318/calcineurin-inhibitor-induced-complement-system-activation-via-erk1-2-signalling-is-inhibited-by-socs-3-in-human-renal-tubule-cells
#12
Beatrix Loeschenberger, Lea Niess, Reinhard Würzner, Hubert Schwelberger, Iris E Eder, Martin Puhr, Julia Guenther, Jakob Troppmair, Michael Rudnicki, Hannes Neuwirt
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations...
November 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29137154/two-sulfur-glycoside-compounds-isolated-from-lepidium-apetalum-willd-protect-nrk52e-cells-against-hypertonic-induced-adhesion-and-inflammation-by-suppressing-the-mapk-signaling-pathway-and-raas
#13
Peipei Yuan, Xiaoke Zheng, Meng Li, Yingying Ke, Yang Fu, Qi Zhang, Xiaolan Wang, Weisheng Feng
Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla...
November 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136956/antagonistic-effect-of-oxytocin-and-tacrolimus-combination-on-adipose-tissue-derived-mesenchymal-stem-cells-antagonistic-effect-of-oxytocin-and-tacrolimus-antagonistic-effect-of-oxytocin-and-tacrolimus
#14
Gozde Sir, Bakiye Goker Bagca, Gurkan Yigitturk, Turker Cavusoglu, Cigir Biray Avci, Cumhur Gunduz, Yigit Uyanikgil
Tacrolimus (FK506) is a chemotherapeutic agent, which uses calcineurin pathway via inhibiting the stimulation of T cells to prevent the formation of immune response in the recipient individual in organ transplants. FK506 is mainly metabolized in the liver by cytochrome P450 enzyme system and is known that it has high toxic effects on different cells. Mesenchymal stem cells (MSCs) have recently gained importance since their potential to be used in cellular therapy and tissue regeneration. In some clinical cases, MSCs are transferred into the patient after the organ transplantations in order to support the treatment...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136764/cardiac-apoptosis-induced-under-high-glucose-condition-involves-activation-of-igf2r-signaling-in-h9c2-cardiomyoblasts-and-streptozotocin-induced-diabetic-rat-hearts
#15
Chih-Chung Feng, Sudhir Pandey, Ching-Yuang Lin, Chia-Yao Shen, Ruey-Lin Chang, Tung-Ti Chang, Ray-Jade Chen, Vijaya Padma Viswanadha, Yueh-Min Lin, Chih-Yang Huang
The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136616/no-relapse-of-calcineurin-inhibitor-associated-thrombotic-microangiopathy-after-discontinuation-of-eculizumab
#16
Thomas Neumann, Andrzej Plis, Martin Weigel, Sylvia Stracke, Sigrun Friesecke, Stephanie-Susanne Stecher, Laila Schneidewind, Christoph Busemann, Christian Andreas Schmidt, William H Krüger
No abstract text is available yet for this article.
November 15, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/29135018/chronic-prurigo-of-nodular-type-a-review
#17
Claudia Zeidler, Athanasios Tsianakas, Manuel Pereira, Hartmut Ständer, Gil Yosipovitch, Sonja Ständer
Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, μ-opioid receptor antagonists, antidepressants or immunosuppressants...
August 23, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#18
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#19
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29130583/endoscopic-retrograde-cholangio-pancreatography-in-the-management-of-biliary-complications-after-paediatric-liver-transplantation
#20
Sivaramakrishnan Venkatesh Karthik, Seng-Hock Quak, Marion M Aw
BACKGROUND: The published paediatric experience with Endoscopic retrograde cholangio-pancreatography (ERCP) in the diagnosis and management of biliary complications following liver transplantation (LT) is limited. AIMS: We describe our experience with ERCP in the management of children following LT who presented with biliary complications, over a 20 year period (1995-2014). METHODS: The retrospectively reviewed data is summarized descriptively...
November 11, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
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