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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/28643798/topical-administration-of-esculetin-as-a-potential-therapy-for-experimental-dry-eye-syndrome
#2
D Jiang, X Liu, J Hu
PurposeIn this study, we investigated the therapeutic effects of topical Esculetin for dry eye rabbits through the ocular tests, inflammatory factor levels and specific phosphorylated protein expressions of ERK1/2 singnal pathway.Patients and methodsThirty-two healthy adult male New Zealand white rabbits were chosen for the study. DES models were established after removing of the main lacrimal gland, Harderian gland and nictitating membrane in the left eyes and randomly divided into group DES control, group CsA, group Esculetin and group Esculetin combined with CsA (C&E), meanwhile the right eyes served as group Normal control...
June 23, 2017: Eye
https://www.readbyqxmd.com/read/28643580/cyclophilins-less-studied-proteins-with-critical-roles-in-pathogenesis
#3
Khushwant Singh, Mark Winter, Miloslav Zouhar, Pavel Rysanek
Cyclophilins (EC 5.2.1.8) (CYPs) belong to a subgroup of proteins known as immunophilins, which also include FK-506 binding proteins (FKBPs) and parvulins. Members of the immunophilins have two main characteristic properties: I) peptidyl-prolyl cis-trans isomerase activity (PPIases) and II) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses...
June 23, 2017: Phytopathology
https://www.readbyqxmd.com/read/28643546/sexual-abuse-within-employment-settings-a-comparison-of-work-related-intra-and-extra-familial-child-molesters
#4
Diana M Falkenbach, Antonia Foehse, Elizabeth Jeglic, Cynthia Calkins, Linsey Raymaekers
Child sexual abuse (CSA) is a serious problem not only in the community but also in institutional settings such as youth-serving organizations, churches, and schools. Although research has started to examine the problem of abuse in institutional settings, there remains a dearth of information about the nature and context of CSA in different employment settings, including those that do not specifically cater to children. In addition, research on the similarities and differences between perpetrators who work with children and other sex offenders is scarce...
June 1, 2017: Sexual Abuse: a Journal of Research and Treatment
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/28639977/topical-delivery-of-immunosuppression-to-prolong-xenogeneic-and-allogeneic-split-thickness-skin-graft-survival
#6
Melissa Mastroianni, Zhi Yang Ng, Ritu Goyal, Christopher Mallard, Evan A Farkash, David A Leonard, Alexander Albritton, Kumaran Shanmugarajah, Josef M Kurtz, David H Sachs, Lauren K Macri, Joachim Kohn, Curtis L Cetrulo
Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)-mediated hyperacute rejection and are lost by POD 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival...
June 7, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28638346/micrornas-in-muscle-characterizing-the-powerlifter-phenotype
#7
Randall F D'Souza, Thomas Bjørnsen, Nina Zeng, Kirsten M M Aasen, Truls Raastad, David Cameron-Smith, Cameron J Mitchell
Powerlifters are the epitome of muscular adaptation and are able to generate extreme forces. The molecular mechanisms underpinning the significant capacity for force generation and hypertrophy are not fully elucidated. MicroRNAs (miRs) are short non-coding RNA sequences that control gene expression via promotion of transcript breakdown and/or translational inhibition. Differences in basal miR expression may partially account for phenotypic differences in muscle mass and function between powerlifters and untrained age-matched controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28634393/a-small-molecule-ds44170716-inhibits-ca-2-induced-mitochondrial-permeability-transition
#8
Naohiro Kon, Atsushi Satoh, Naoki Miyoshi
Mitochondria are involved in a variety of physiological and pathological processes. Ca(2+) uptake is one of the important functions of the organelle for maintenance of cellular Ca(2+) homeostasis. In pathological conditions such as ischemia reperfusion injury, Ca(2+) overload into mitochondria induces mitochondrial permeability transition (MPT), a critical step for cell death. Because inhibition of MPT is a promising approach to protecting cells and organs, it is important for drug discovery to identify novel chemicals or mechanisms to inhibit MPT...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634032/ciclosporin-use-in-epidermal-necrolysis-is-associated-with-an-important-mortality-reduction-evidence-from-three-different-approaches
#9
C González-Herrada, S Rodríguez-Martín, L Cachafeiro, V Lerma, O González, J A Lorente, A Rodríguez-Miguel, J González-Ramos, G Roustan, E Ramírez, T Bellón, F J de Abajo
Several immunomodulatory agents are used in the treatment of Epidermal Necrolysis (EN), but evidence of their efficacy is limited. The Autonomous Community of Madrid has two reference Burn Units (BUs) to which all patients with EN are referred to. One BU has mostly used ciclosporin (CsA), while the other has used non-CsA therapies (mainly high-dose intravenous immunoglobulin). The allocation of patients to one or another BU was mainly based on proximity resembling a random assignment. Thus, we took advantage of this "natural experiment" to estimate the mortality risk ratio (MRR) of CsA (N=26) as compared to non-CsA (n=16) using hospital as an instrumental variable (IV) over the period 2001-2015...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#10
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#11
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
June 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28629918/trajectories-of-emergent-central-sleep-apnea-during-continuous-positive-airway-pressure-therapy
#12
Dongquan Liu, Jeff Armitstead, Adam Benjafield, Shiyun Shao, Atul Malhotra, Peter A Cistulli, Jean-Louis Pepin, Holger Woehrle
BACKGROUND: Emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in ≈10% of OSA titration studies. This study assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy. METHODS: US telemonitoring device data were analyzed for the presence/absence of emergent CSA at baseline (Week 1) and Week 13. Defined groups were: obstructive sleep apnea (OSA; average central apnea index [CAI] <5/hour in Week 1, <5/hour in Week 13); transient CSA (CAI ≥5/hour in Week 1, <5/hour in Week 13); persistent CSA (CAI ≥5/hour in Week 1, ≥5/hour in Week 13); emergent CSA (CAI <5/hour in Week 1, ≥5/hour in Week 13)...
June 16, 2017: Chest
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
#13
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/28623616/cyclosporine-a-mediated-il-6-expression-promotes-neural-induction-in-pluripotent-stem-cells
#14
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/28623111/reversal-of-abcb1-mediated-efflux-by-imatinib-and-nilotinib-in-cells-expressing-various-transporter-levels
#15
Petr Mlejnek, Petr Kosztyu, Petr Dolezel, Susan E Bates, Eliska Ruzickova
Recently, it has been suggested that imatinib (IM) and nilotinib (NIL) could be studied beyond their original application, as inhibitors of the drug efflux pump ABCB1 (P-glycoprotein, MDR1). Since the reversal of ABCB1-mediated resistance has never been successfully demonstrated in the clinic, we addressed the question of whether IM and NIL may actually serve as efficient inhibitors of ABCB1. Here we define an efficient inhibitor as a compound that achieves full (90-100%) reversal of drug efflux at a concentration that does not exhibit significant off-target toxicity in vitro...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28622884/the-effect-of-caloric-restriction-on-the-forelimb-skeletal-muscle-fibers-of-the-hypertrophic-myostatin-null-mice
#16
Mohamed I Elashry, Antonios Matsakas, Sabine Wenisch, Stefan Arnhold, Ketan Patel
Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized...
June 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28620719/large-coverage-mr-neurography-in-cidp-diagnostic-accuracy-and-electrophysiological-correlation
#17
Moritz Kronlage, Philipp Bäumer, Kalliopi Pitarokoili, Daniel Schwarz, Véronique Schwehr, Tim Godel, Sabine Heiland, Ralf Gold, Martin Bendszus, Min-Suk Yoon
The objective of this study was to evaluate large coverage magnetic resonance neurography (MRN) in chronic inflammatory demyelinating polyneuropathy (CIDP). In this prospective study, 18 patients with CIDP and 18 healthy controls were examined by a standardized MRN protocol at 3 T. Lumbosacral plexus was imaged by a T2-weighted 3D sequence and peripheral nerves of the upper and lower extremity by axial T2-weighted turbo spin-echo sequences. Lesions were characterized by nerve cross-sectional area (CSA) and T2-weighted signal (nT2)...
June 15, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28620014/the-tendinopathic-achilles-tendon-does-not-remain-iso-volumetric-upon-repeated-loading-insights-from-3d-ultrasound
#18
Leila Nuri, Steven J Obst, Richard Newsham-West, Rod S Barrett
Mid-portion Achilles tendinopathy (MAT) alters the normal three-dimensional (3D) morphology of the Achilles tendon (AT) at rest and under a single tensile load. However, how MAT changes the 3D morphology of AT during repeated loading remains unclear. This study compared the AT longitudinal, transverse and volume strains during repeated loading in MAT with those of the contralateral tendon in people with unilateral MAT. Ten adults with unilateral MAT performed 10 successive 25 second submaximal (50%) voluntary isometric plantarflexion contractions with both legs...
June 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28619100/cyclophilin-b-facilitates-the-replication-of-orf-virus
#19
Kui Zhao, Jida Li, Wenqi He, Deguang Song, Ximu Zhang, Di Zhang, Yanlong Zhou, Feng Gao
BACKGROUND: Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored...
June 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28618294/focused-high-resolution-sonography-of-the-suprascapular-nerve-a-simple-surrogate-marker-for-neuralgic-amyotrophy
#20
Leonhard Gruber, Alexander Loizides, Wolfgang Löscher, Bernhard Glodny, Hannes Gruber
OBJECTIVES: To define the diagnostic value of high-resolution ultrasound (HRUS) of the suprascapular nerve (SSN) in the diagnosis of neuralgic amyotrophy (NA). METHODS: The cross-section areas (CSA) of the SSN at the C5 root (CSA1) and the omohyoid muscle in the midclavicular line (CSA2) were assessed bilaterally in 15 healthy volunteers and 14 patients with clinically and electrophysiologically verified NA. Receiver-operator-characteristics (ROC) curves were generated and cut-off values, sensitivity, specificity, positive (PPV) and negative predictive values (NPV), likelihood (LR) and odds ratios (OR) were calculated...
May 19, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
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