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https://www.readbyqxmd.com/read/28439730/physiological-and-therapeutic-regulation-of-pcsk9-activity-in-cardiovascular-disease
#1
REVIEW
Simon Glerup, Rainer Schulz, Ulrich Laufs, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and is accelerated by increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in the understanding of PCSK9 biology have been reported illustrating how PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28434550/renal-failure-after-cardiac-operations-not-all-acute-kidney-injury-is-the-same
#2
Todd C Crawford, J Trent Magruder, Joshua C Grimm, Shin-Rong Lee, Alejandro Suarez-Pierre, David Lehenbauer, Christopher M Sciortino, Robert S Higgins, Duke E Cameron, John V Conte, Glenn J Whitman
BACKGROUND: The Society of Thoracic Surgeons (STS) database does not distinguish between a decline in creatinine clearance vs new hemodialysis (HD) when qualifying acute renal failure (ARF) after a cardiac operation. We hypothesized that patients requiring HD experience significantly greater postoperative morbidity and death. METHODS: We included all patients who underwent STS index cardiac operations at our institution from 2008 to March 2015 and did not have preexisting renal failure (creatinine >4...
April 20, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28429121/renovascular-hypertension-results-in-adulthood-of-renal-autotransplantation-performed-in-children
#3
Bertrand Chavent, Ambroise Duprey, Marie-Pierre Lavocat, Christine Fichtner, Anne-Marie Beraud, Jean-Noel Albertini, Jean-Pierre Favre, Nicolas Maillard, Xavier Barral
BACKGROUND: This study describes the long-term results of renal autotransplantation for renovascular hypertension performed in children who are now 21 years of age or older. METHODS: Sixteen children (4 boys, 12 girls) with a mean age of 11.2 years at the time of the procedure underwent ex-vivo surgery at the university hospital of Saint-Etienne between 1992 and 2008. Acetylsalicylic acid was used for antiplatelet therapy in the postoperative period, without routine anticoagulation...
April 20, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28424464/-18-f-tetrafluoroborate-pet-ct-enables-sensitive-tumor-and-metastasis-in-vivo-imaging-in-a-sodium-iodide-symporter-expressing-tumor-model
#4
S Diocou, A Volpe, M Jauregui-Osoro, M Boudjemeline, K Chuamsaamarkkee, F Man, P J Blower, T Ng, G E D Mullen, G O Fruhwirth
Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [(18)F]tetrafluoroborate ([(18)F]BF4(-)) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424218/gop-1-promotes-apoptotic-cell-degradation-by-activating-the-small-gtpase-rab2-in-c-elegans
#5
Jianhua Yin, Yaling Huang, Pengfei Guo, Siqi Hu, Sawako Yoshina, Nan Xuan, Qiwen Gan, Shohei Mitani, Chonglin Yang, Xiaochen Wang
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within plasma membrane-derived phagosomes. Maturation of phagosomes involves a series of membrane-remodeling events that are governed by the sequential actions of Rab GTPases and lead to formation of phagolysosomes, where cell corpses are degraded. Here we identified gop-1 as a novel regulator of apoptotic cell clearance in Caenorhabditis elegans Loss of gop-1 affects phagosome maturation through the RAB-5-positive stage, causing defects in phagosome acidification and phagolysosome formation, phenotypes identical to and unaffected by loss of unc-108, the C...
April 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28416609/cd36-regulates-malaria-induced-immune-responses-primarily-at-early-blood-stage-infection-contributing-to-parasitemia-control-and-resistance-to-mortality
#6
Ramesh P Thylur, Xianzhu Wu, Nagaraj M Gowda, Kishore Punnath, Shivayogeeshwara E Neelgund, Maria Febbraio, D Channe Gowda
In malaria, CD36 plays several roles including mediating parasite sequestration to host organs, phagocytic clearance of parasites and regulation of immunity. While the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and Cd36-/- mice infected with a nonlethal strain of Plasmodium yoelii...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28416165/influence-of-cardiovascular-risk-in-the-prediction-and-timing-of-cardiac-events-after-exercise-echocardiogram-testing-without-ischemia
#7
Sonia Velasco Del Castillo, Ane Antón Ladislao, Verónica Gómez Sánchez, José Juan Onaindia Gandarias, Ángela Cacicedo Fernández de Bobadilla, Ibon Rodríguez Sánchez, Eva Laraudogoitia Zaldumbide
INTRODUCTION AND OBJECTIVES: There have been no analyses of the influence of cardiovascular risk as a predictor of events in patients with exercise echocardiography (EE) without ischemia. Our objective was to determine the predictors of cardiac events, paying special attention to cardiovascular risk. METHODS: This study included 1640 patients with EE without ischemia. Of these, there were 1206 with no previously known coronary artery disease (CAD), whose risk of a fatal cardiovascular disease event was estimated according to the European SCORE (Systematic COronary Risk Evaluation) risk assessment system, and 434 with known CAD...
April 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28414310/autophagy-supports-generation-of-cells-with-high-cd44-expression-via-modulation-of-oxidative-stress-and-parkin-mediated-mitochondrial-clearance
#8
K A Whelan, P M Chandramouleeswaran, K Tanaka, M Natsuizaka, M Guha, S Srinivasan, D S Darling, Y Kita, S Natsugoe, J D Winkler, A J Klein-Szanto, R K Amaravadi, N G Avadhani, A K Rustgi, H Nakagawa
High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44(Low)-CD24(High) (CD44L) cells give rise to CD44(High)-CD24(-/Low) (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-β...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28414292/dendritic-cells-expressing-immunoreceptor-cd300f-are-critical-for-controlling-chronic-gut-inflammation
#9
Ha-Na Lee, Linjie Tian, Nicolas Bouladoux, Jacquice Davis, Mariam Quinones, Yasmine Belkaid, John E Coligan, Konrad Krzewski
Proinflammatory cytokine overproduction and excessive cell death, coupled with impaired clearance of apoptotic cells, have been implicated as causes of failure to resolve gut inflammation in inflammatory bowel diseases. Here we have found that dendritic cells expressing the apoptotic cell-recognizing receptor CD300f play a crucial role in regulating gut inflammatory responses in a murine model of colonic inflammation. CD300f-deficient mice failed to resolve dextran sulfate sodium-induced colonic inflammation as a result of defects in dendritic cell function that were associated with abnormal accumulation of apoptotic cells in the gut...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28408835/predictors-of-common-femoral-artery-access-site-complications-in-patients-on-oral-anticoagulants-and-undergoing-a-coronary-procedure
#10
Nicolas W Shammas, Gail A Shammas, Susan Jones-Miller, Mileah Rose Gumpert, Miranda Jade Gumpert, Christine Harb, Majid Z Chammas, W John Shammas, Rommy A Khalafallah, Amy Barzgari, Bassel Bou Dargham, Ghassan E Daher, Rayan Jo Rachwan, Andrew N Shammas
BACKGROUND: It is unclear whether patients on oral anticoagulants (OAC) undergoing a procedure using common femoral artery access have higher adverse events when compared to patients who are not anticoagulated at the time of the procedure. METHODS: We retrospectively reviewed data from consecutive patients who underwent a cardiac procedure at a tertiary medical center. Patients were considered (group A) fully or partially anticoagulated if they had an international normalized ratio (INR) ≥1...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28408159/brain-mrs-glutamine-as-a-biomarker-to-guide-therapy-of-hyperammonemic-coma
#11
Anne H O'Donnell-Luria, Alexander P Lin, Sai K Merugumala, Frances Rohr, Susan E Waisbren, Rebecca Lynch, Vatche Tchekmedyian, Aaron D Goldberg, Andrew Bellinger, J Ricardo McFaline-Figueroa, Tracey Simon, Esteban F Gershanik, Bruce D Levy, David E Cohen, Martin A Samuels, Gerard T Berry, Natasha Y Frank
Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate...
March 10, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28402699/inhibition-of-retrograde-transport-modulates-misfolded-protein-accumulation-and-clearance-in-motoneuron-diseases
#12
Riccardo Cristofani, Valeria Crippa, Paola Rusmini, Maria Elena Cicardi, Marco Meroni, Nausicaa V Licata, Gessica Sala, Elisa Giorgetti, Christopher Grunseich, Mariarita Galbiati, Margherita Piccolella, Elio Messi, Carlo Ferrarese, Serena Carra, Angelo Poletti
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial...
April 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28396396/formation-of-neurodegenerative-aggresome-and-death-inducing-signaling-complex-in-maternal-diabetes-induced-neural-tube-defects
#13
Zhiyong Zhao, Lixue Cao, E Albert Reece
Diabetes mellitus in early pregnancy increases the risk in infants of birth defects, such as neural tube defects (NTDs), known as diabetic embryopathy. NTDs are associated with hyperglycemia-induced protein misfolding and Caspase-8-induced programmed cell death. The present study shows that misfolded proteins are ubiquitinylated, suggesting that ubiquitin-proteasomal degradation is impaired. Misfolded proteins form aggregates containing ubiquitin-binding protein p62, suggesting that autophagic-lysosomal clearance is insufficient...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395093/repatriation-of-human-remains-following-death-in-international-travellers
#14
Ruairi Connolly, Richard Prendiville, Denis Cusack, Gerard Flaherty
Background: Death during international travel and the repatriation of human remains to one's home country is a distressing and expensive process. Much organization is required involving close liaison between various agencies. Methods: A review of the literature was conducted using the PubMed database. Search terms included: 'repatriation of remains', 'death', 'abroad', 'tourism', 'travel', 'travellers', 'travelling' and 'repatriation'. Additional articles were obtained from grey literature sources and reference lists...
March 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28390095/the-anti-trichomonas-vaginalis-phloroglucinol-derivative-isoaustrobrasilol-b-modulates-extracellular-nucleotides-hydrolysis
#15
Camila Braz Menezes, Graziela Vargas Rigo, Henrique Bridi, Danielle da Silva Trentin, Alexandre José Macedo, Gilsane Lino Von Poser, Tiana Tasca
Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from Southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase and ecto-5'-nucleotidase, represents new targets for combating protozoa. This study investigated the activity of phloroglucinol derivatives of Hypericum species from Southern Brazil against T...
April 8, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28390094/early-experience-with-hypothermic-machine-perfusion-of-living-donor-kidneys
#16
Michael Moser, Nathan Ginther, Yigang Luo, Gavin Beck, Ronn Ginther, Marla Ewen, Rhianna Matsche-Neufeld, Ahmed Shoker, Grzegorz Sawicki
BACKGROUND: Although hypothermic machine perfusion (HMP) has been shown to be beneficial to deceased donor kidneys, the effect of HMP on Living Donor Kidneys (LDK) is unknown. LDK are subjected to minutes of normothermic ischemia at the time of recovery. METHODS: Comparison of 16 LDK preserved by HMP with 16 LDK preserved by static cold storage (SCS). Outcomes of interest are resistive indices (RI), both while on HMP and postoperatively, and creatinine clearance (CrCl)...
April 8, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28389661/crispr-cas9-mediated-pd-1-disruption-enhances-anti-tumor-efficacy-of-human-chimeric-antigen-receptor-t-cells
#17
Levi J Rupp, Kathrin Schumann, Kole T Roybal, Rachel E Gate, Chun J Ye, Wendell A Lim, Alexander Marson
Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389316/maintenance-therapy-with-vinflunine-plus-best-supportive-care-versus-best-supportive-care-alone-in-patients-with-advanced-urothelial-carcinoma-with-a-response-after-first-line-chemotherapy-maja-sogug-2011-02-a-multicentre-randomised-controlled-open-label-phase
#18
Jesus García-Donas, Albert Font, Begoña Pérez-Valderrama, José Antonio Virizuela, Miquel Ángel Climent, Susana Hernando-Polo, José Ángel Arranz, Maria Del Mar Llorente, Nuria Lainez, José Carlos Villa-Guzmán, Begoña Mellado, Aránzazu González Del Alba, Daniel Castellano, Enrique Gallardo, Urbano Anido, Xavier García Del Muro, Montserrat Domènech, Javier Puente, Rafael Morales-Barrera, Jose Luis Pérez-Gracia, Joaquim Bellmunt
BACKGROUND: Maintenance therapy improves outcomes in various tumour types, but cumulative toxic effects limit the choice of drugs. We investigated whether maintenance therapy with vinflunine would delay disease progression in patients with advanced urothelial carcinoma who had achieved disease control with first-line chemotherapy. METHODS: We did a randomised, controlled, open-label, phase 2 trial in 21 Spanish hospitals. Eligible patients had locally advanced, surgically unresectable, or metastatic transitional-cell carcinoma of the urothelial tract, adequate organ function, and disease control after four to six cycles of cisplatin and gemcitabine (carboplatin allowed after cycle four)...
April 4, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28388672/toxicity-of-benthic-dinoflagellates-on-grazing-behavior-and-survival-of-the-brine-shrimp-artemia-salina
#19
Raquel A F Neves, Tainá Fernandes, Luciano Neves Dos Santos, Silvia M Nascimento
Harmful algae may differently affect their primary grazers, causing sub-lethal effects and/or leading to their death. The present study aim to compare the effects of three toxic benthic dinoflagellates on clearance and grazing rates, behavioral changes, and survival of Artemia salina. Feeding assays consisted in 1-h incubations of brine shrimps with the toxic Prorocentrum lima, Gambierdiscus excentricus and Ostreopsis cf. ovata and the non-toxic Tetraselmis sp. Brine shrimps fed unselectively on all toxic and non-toxic algal preys, without significant differences in clearance and ingestion rates...
2017: PloS One
https://www.readbyqxmd.com/read/28388439/celastrol-induced-nur77-interaction-with-traf2-alleviates-inflammation-by-promoting-mitochondrial-ubiquitination-and-autophagy
#20
Mengjie Hu, Qiang Luo, Gulimiran Alitongbieke, Shuyi Chong, Chenting Xu, Lei Xie, Xiaohui Chen, Duo Zhang, Yuqi Zhou, Zhaokai Wang, Xiaohong Ye, Lijun Cai, Fang Zhang, Huibin Chen, Fuquan Jiang, Hui Fang, Shanjun Yang, Jie Liu, Maria T Diaz-Meco, Ying Su, Hu Zhou, Jorge Moscat, Xiangzhi Lin, Xiao-Kun Zhang
Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling...
April 6, 2017: Molecular Cell
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