tbuckley/cabot-search huggingface dataset:
Abstract 872: Inhibition of Spinal Astrocytes Activation Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating NGF/TRPV1 Nociceptive Signaling
Authors: Shufang He, Rongrong Liu, Li zhang, Ye Zhang
Journal: Circulation Research (2019)

Background and Aim: Spinal astrocytes activation are implicated in nociception and pain processing after noxious stimuli, while its role in cardiac ischemic nociception is unknown. We recently reported spinal nerve growth factor (NGF)-sensitized transient receptor potential vanilloid 1 (TRPV1) nociceptive signaling following cardiac ischemia and reperfusion (I/R). This study was design to investigate whether spinal astrocytes are activated following myocardial I/R and its effects on spinal NGF-TRPV1 signaling. Methods and Results: Myocardial I/R injury was induced by 30 min occlusion of the left coronary artery followed by 120 min of reperfusion in rats. Glial fibrillary acidic protein (GFAP), an astrocyte marker, was found up-regulated in thoracic spinal cord during ischemia and reperfusion. Intrathecally pre-injection of fluorocitrate (FC), an astrocyte inhibitor, reduced infarct size (IS/AAR, area at risk), from 48.4±2.67 to 29.7±3.13 (P&lt;0.05, Fig.1 A). The high level of cardiac troponin T caused by I/R was decreased by FC injection as well (from 530±65 to 129±50 μg/μl, P&lt;0.01, Fig.1 B). Upon immunofluorescence staining, GFAP immunopositive cells in spinal cord were found markedly increased after I/R, while the staining was suppressed by intrathecal FC administration (Fig.1 C). Moreover, the up-regualtion of NGF and TRPV1 protein levels in spinal cord were both inhibited by FC pretreatment (Fig.1 D-F). Conclusion: Myocardial I/R induced the activation of spinal astrocytes, inhibition of which reduces infarct size and cTnT level, as well as NGF-TRPV1 signaling, which suggests a novel therapeutic target for preventing myocardial ischemic injury.
Safely Improving the in Vivo Survival of Tumor Specific Cytotoxic T Lymphocytes by Co-Transfer of IL7 Receptor Alpha Chain and icaspase9
Authors: Juan F Vera, Valentina Hoyos, Barbara Savoldo, Concetta Quintarelli, Greta A Giordano, Ann M. Leen, Hao Liu, Aaron E. Foster, Helen E. Heslop, Cliona M Rooney, Malcolm K Brenner, Gianpietro Dotti
Journal: Blood (2008)
A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors
Authors: Guy Young, Ri Liesner, Tiffany Chang, Robert Sidonio, Johannes Oldenburg, Victor Jiménez-Yuste, Johnny Mahlangu, Rebecca Kruse-Jarres, Michael Wang, Marianne Uguen, Michelle Y. Doral, Lilyan Y. Wright, Christophe Schmitt, Gallia G. Levy, Midori Shima, Maria Elisa Mancuso
Journal: Blood (2019)
Local leukocyte elastase release at site of occlusive plaque rupture predicts downstream microvascular reperfusion injury and impaired left ventricular function in ST elevation myocardial infarction
Authors: Mark Nallaratnam, Tessa Mocatta, Catriona J. Marshall, David Smyth, Christine C. Winterbourn, John Elliott, A. Mark Richards, Anthony J. Kettle, Dougal R. McClean
Journal: Journal of the American College of Cardiology (2008)
Abstract 866: Cardiac-specific Deletion of General Control of Amino-Acid Synthesis 5-like 1 Regulates Fatty Acid Oxidation in Diet Induced Obesity
Authors: Dharendra Thapa, Janet R Manning, Michael W Stoner, Manling Zhang, Iain Scott
Journal: Circulation Research (2019)

Background: Healthy hearts use several fuel substrates for energy metabolism, with fatty acid oxidation (FAO) accounting for ~70% of total ATP production. Lack of flexibility to utilize different substrates, and a shift towards increased fatty acid utilization, is a key feature of obesity and diabetes. We previously reported that increased acetylation of several mitochondrial FAO enzymes, regulated in part via increased abundance of the mitochondrial acetyltransferase GCN5L1, correlated with increased enzymatic activity and FAO in the heart. The focus of the current study was to investigate whether decreased acetylation, via cardiac depletion of GCN5L1, regulates cardiac energy metabolism following exposure to a high fat diet (HFD). Hypothesis: We hypothesize that decreased acetylation of metabolic enzymes in GCN5L1 cardiac KO (cKO) mice may limit excessive cardiac FAO activity and improve glucose utilization under HFD conditions. Furthermore, we postulate that this metabolic phenotype would result in improved mitochondrial bioenergetic output and cardiac function. Methods: To examine the role of GCN5L1 in regulating mitochondrial protein acetylation, immunoprecipitation with acetylated lysine antibodies was performed to assess the acetylation status of metabolic proteins. Western blots and qPCR were performed to quantitate protein and mRNA expression levels. Further, metabolic enzyme activities were analyzed in vitro . Finally, cardiac workload was measured ex vivo to assess changes in cardiac function. Results: We found that increased mitochondrial protein acetylation under HFD conditions was significantly decreased in GCN5L1 cKO mice relative to WT. This decrease correlated with reduced acetylation of the FAO enzymes SCAD and HADHA in GCN5L1 cKO mice. HFD exposure led to increased cardiac FAO enzyme activity in WT animals, which was reduced in GCN5L1 cKO animals. Finally, a significant decrease in cardiac workload observed in WT animals was not present in GCN5L1 cKO animals under HFD conditions. Conclusions: These findings indicate that decreased acetylation of FAO proteins via cardiac depletion of GCN5L1 results in decreased cardiac FAO utilization and enzymatic activity under HFD conditions.
Abstract 876: Chronic GPER1 Cardioprotection in H9c2 Myoblasts is Mediated by an MST1-YAP Pathway and Mitochondrial Function and Dynamics
Authors: Ngonidzashe Madungwe, Yansheng Feng, Jean C Bopassa
Journal: Circulation Research (2019)

Introduction: We recently showed that cardiac tissue treated acutely with estrogen (17β-estradiol; E2), pre- and post-ischemia, exhibited reduced myocardial infarct size and better functional recovery after ischemia /reperfusion via the G protein-coupled estrogen receptor 1 (GPER1). These E2-GPER1 cardioprotective effects have been found to involve the preservation of mitochondrial structure and function. Here, we investigate the impact and mechanisms underlying chronic GPER1 activation in H9c2 cardiac myoblasts treated with a cytotoxic agent, H 2 O 2 . Methods: H9c2 cells were treated with 200 μM H 2 O 2 , for 24 h and reoxygenated in no-serum conditions for 4 and 8 days with the addition of E2 (80nM) and GPER1 agonist (G1; 100nM) and GPER1 antagonist (G15; 1μM). We measured cell death and proliferation, as well as gene expression, mitochondrial morphology and function using flow cytometry, cell assays, qRT-PCR, along with fluorescence and electron microscopy. We also analyzed cell lysates by Western blot to assess the mechanisms involved. Results: We found that chronic treatment of cardiac myoblasts with E2 and G1 results in reduced cell death. The surviving cells showed improved mitochondrial function as evidenced by better cristae morphology, increased ATP production and increased resistance to opening of the mitochondrial permeability transition pore. Particularly chronic GPER1 activation led to reduced cell cycle activity along with changes in mitochondrial dynamics of fusion and fission. Additionally, we found that chronic GPER1 activation signaling involves decreased phosphorylation of mammalian sterile-20-like kinase (MST1) and increased translocation of the transcription coactivator, yes-associated protein (YAP), to the nucleus for upregulation of pro-survival genes. These effects were mainly prevented by the G15, suggesting a GPER1-dominant mechanism. Conclusion: Chronic GPER1 activation in H9c2 cardiac myoblasts treated with oxidative stress results in reduced cell death by preserving mitochondrial structural integrity and function by increasing mitochondrial dynamics. This chronic GPER1 cardioprotection involves activation of MST1/YAP signaling pathways as well as upregulation of pro-survival gene.
Pneumococcal Vaccination (PCV13) Prior to Initiation of Immunosuppressive Therapy in Patients with Hematological Malignancies Is Associated with Decrease Morbidity and Decrease Hospitalizations
Authors: Regina Draliuk, Iveta Mintsman, Alla Shnaider, Shuras Viky, Rotem Benami, Noga Salem, Olga Valkovsky, Mouna Ballan Haj, Evelyne Shabad, Antonio Kotler, Elena Mishchenko, Meir Preis
Journal: Blood (2018)
Abstract 751: The Inhibition of PARP Provides Greatercardioprotection in Mice With Heart Failure
Authors: Manami Katoh, Seitaro Nomura, Toshiyuki Ko, Kanna Fujita, Shintaro Yamada, Masamichi Ito, Hiroyuki Aburatani, Issei Komuro
Journal: Circulation Research (2019)

The most cause of death in Japan is cancer and the second is heart disease. It is expected that the number of patients with both diseases will continue to increase in the increasingly aging society. Cardiotoxicity by anticancer agents has been recognized for a long time, for example alkylating agents, antimetabolites, proteasome inhibitors, and anthracycline anticancer agents. As cancer patients and heart failure patients increase, the number of patients suffering both diseases at the same time will naturally increase. In recent years, many new anticancer drugs have been developed and are on the market in succession, and the research on cardiotoxicity in each drug has not kept up. In 2017, from our group, there was a report that inflammation was caused by an increase in cardiomyocyte single strand breaks in pressure-overload heart failure model mice, and that inflammation contributes to declining cardiac function . DNA repair related protein PARP1 plays an important role in the repair mechanism of SSBs. PARP inhibitor disturbs its mechanism and exerts antitumor effect by causing tumor cells to become apoptosis. Therefore, we hypothesize that orally administered PARP inhibitors in heart failure patients will inhibit DNA repair by PARP, thus exacerbate inflammation and impair cardiac function more. To examine this hypothesis, we administered a representative PARP inhibitor, olaparib to pressure-overload heart failure model mice. Surprisingly, the cardiac function was improved in the olaparib administrated group. PARP is known to recruit DNA repair related proteins through synthesis of PAR (Poly-ADP-Ribose) on the DNA damage sites. In recent reports, several studies have shown that the accumulation of PAR would be involved in the worsening of the disease state in cerebellar degenerative ataxia and Parkinson's disease. In our immunostaining study of PAR using the heart tissue specimens from 58 patients with dilated cardiomyopathy, PAR was stained much more in patients with poor outcomes. I believe that PARP inhibitors may have a cardioprotective effect by preventing the accumulation of PAR, and we are now conducting further analyzes.
Abstract 776: <i>MYBPC3</i> Mutations in Indian Patients With Hypertrophic Cardiomyopathy
Authors: Varsha W Wankhade
Journal: Circulation Research (2019)

Introduction: Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is characterized by thickening of the ventricular wall, myocyte disarray, and fibrosis, resulting in impaired cardiac function and leading to adverse ventricular remodeling, heart failure and increased risk for sudden cardiac death. Importantly, mutations in the gene encoding cardiac myosin binding protein-C ( MYBPC3 ), a muscle contractile protein,account for approximately 50% of the reported HCM cases. However, the prevalence of penetrance of MYBPC3 mutations in Indian patients with HCM is yet to be systematically studied. Methods: The Institutional Human Ethics Committee at the University of Puneapproved the present study. HCM patients undergoing treatment in theCardiology Unit of Bharti Hospital, Pune, were identified. With the approval of written informed consent, blood samples were obtained from all patients and their relatives and screened by single-strand conformation polymorphism (SSCP) and direct DNA sequencing, followed by correlation with clinical outcome. Results: Of the 23 probands screened in this study, one, #16, showed a mutation in exon 07 (A/G) at chromosomal position 47370041, causing a protein change at position NP_000247.2:p.S236G, and reported as SNP status ID rs386584787. The mutation was localizedto the immunoglobulin domain of cardiac myosin binding protein-C, causing an amino acid change from serine to glycine with a score of 0.00, as shown by thePolyPhen-2 (Polymorphism Phenotyping v2) tool.G&gt;C transversion of intron variant in exon 21 of MYBPC3 results in a new exon splicing enhancer (ESE) site which may alter splicing. G&gt;A transition at g. 20167 is an intron variant of a previously reported status (rs373904644). This polymorphism results in the creation of an intronic splicingenhancer (ISE) site. The proband had left ventricular wall thickness of 24 mm, ejection fraction of 60 (%), and left ventricular internal diameter of 30 mm, suggesting early onset of HCM. Conclusion: The MYBPC3 mutations might play a key role in thedevelopment of HCM in the Indian population, indicating the soundness of establishing a systematic screening of all HCM patients.
Evaluation of an NCCN guideline-based weight management pathway on weight loss in female breast cancer patients.
Authors: Damien Mikael Hansra, Eugene R Ahn, Nathan Schoeber, Jennifer Cargile, Anita Johnson, Ricardo H. Alvarez
Journal: Journal of Clinical Oncology (2019)

301 Background: Obesity is a risk factor for many breast cancer (BC) subtypes &amp; is associated w/ inferior BC outcomes. Here, we investigate the effect of a NCCN based intervention on weight loss (WL) in BC pts. Methods: Prospective study using WL guidelines adapted from NCCN Survivorship (V. 2.2017). Data collected: demographics, clinical, cardiovascular risk factors (CVD), weight, height, body fat%. Stats: 1 sample T-Test w/ 2 tail p-value &amp; 95% CI used to calculate change in weight from baseline to 3 &amp; 6 months (mo) using hypothetical mean of 0. Inclusions: Female BC pts, stage 0-III, OW (BMI &gt; 25mg/m2) or OB (BMI &gt; 30kg/m2). Exclusions: No BC, stage IV, not OW/OB, lost to follow up (f/u), non-compliance, death, or recurrent disease. Intervention: BMI assessed at baseline at initial visit where pt received 20 minute OB counseling by oncologist (ONC). Pts include NEW pts (treatment &amp; surgery naïve) &amp; F/U pts (pts finished definitive treatment in survivorship). ONC counseling included pt education on OB &amp; cancer outcomes &amp; CVD risk. Initially, pts referred to physical therapy (PT) for exercise program &amp; dietician (DT) for nutrition counseling. Pts visit PT &amp; DT q 3 mo. ONC counseling provided periodically during scheduled visits. Results: 70 pts enrolled 10/26/2017 – 10/8/2018. Median pt age = 56 yrs (37-87). Menopausal status: 25/70 (36%) pre menopause vs. 45/70 (64%) post menopause. Race: 29/70 Caucasian (41%), 41/70 (59%) African American, 0/70 (0%) other. Ethnicity: 2/70 (3%) Latin vs. 68/70 (97%) non-Latin. Avg. BMI = 34 kg/m2 (26-54). Avg. weight = 90 kg (61-143). Stage: 0 = 7/70 (10%) , I = 26/70 (37%), II = 21/70 (30%), III = 16/70 (23%). Receptors: 12/70 (17%) triple negative, 13/70 (19%) Her-2+, 49/70 (70%) ER/PR+. CVD risk factors &amp; body fat% shown separately. Mean WL for the 70 pts (NEW + F/U, N = 70) = -0.7 kg @ 3 mo. (p = 0.08), 95%CI (-1.510- +0.101); mean WL = -0.7 kg @ 6 mo. (p = 0.16), 95%CI (-1.703-+0.295). Mean WL for NEW pts, (N = 52) lost -0.9 kg @ 3 mo. (p = 0.0467), 95%CI (-1.809- -0.014). New pts lost -0.7 kg @ 6 mo. (p = 0.21), 95% CI (-1.868 - +0.440). Conclusions: Implementation of the NCCN guidelines + ONC counseling as part of a WL program mitigates weight gain @ 3 &amp; 6 mo in all OW &amp; OB BC pts &amp; induced significant weight loss in NEW pts @ 3 mo.
Use and patient affordability of opioid analgesics for cancer pain management in different regions of China: a retrospective analysis of data from 2006 to 2016
Authors: Zhiran Huang, Xiawen Su, Yifan Diao, Shiyang Liu, Mengjia Zhi, Shuai Geng, Jing Sun, Yuanli Liu
Journal: The Lancet (2019)
Abstract 289: Neddylation is Essential for Cardiac Metabolic Maturation in the Developing Heart
Authors: Jianqiu Zou, Jie Li, Rodney Littlejohn, Yali Yao, Kunzhe Dong, Jiliang Zhou, Weiqin Chen, Huabo Su
Journal: Circulation Research (2019)

Changes in metabolic milieu during development trigger a metabolic shift from fetal-type glycolysis to adult-type fatty acid oxidation in the developing heart. Disruption of this metabolic shift has been linked to congenital heart disease, a major cause of birth-related mortality and morbidity worldwide. Neddylation is a post-translational modification that covalently attaches a small ubiquitin-like protein, NEDD8, to target proteins. Previously we reported that neddylation is essential for cardiomyocyte proliferation through sustaining the YAP signaling. However, a link between neddylation and cardiac metabolic maturation has not yet been established. Here, we abrogated neddylation by cardiac-specific deletion of NAE1, an essential subunit of the sole NEDD8 E1 enzyme, via αMHC Cre in mice, which led to significant reduction of NAE1 proteins and neddylated proteins in the heart. Temporal histological and functional analyses revealed that mice lacking neddylation displayed cardiac hypoplasia and ventricular non-compaction at E16.5, which became more pronounced by P1, eventually leading to heart failure and perinatal lethality by P7. Transcriptome analysis identified that the defects in cardiac chamber maturation are associated with upregulation of glycolytic genes and downregulation of oxidative metabolic genes. Transmissive electron microcopy revealed accumulation of lipid droplets and degenerative/immature mitochondria in hearts deficient of neddylation. In vitro, pharmacological inhibition of neddylation impairs mitochondrial membrane potential and respiration, and suppresses fatty acid utilization in oleic acid-primed cultured cardiomyocytes. Mechanistically, HIF1α, a potent regulator of cardiac metabolic reprogramming, is a novel NEDD8 target. Inhibition of neddylation causes accumulation of HIF1α proteins and consequently disrupts the expression of HIF1α downstream targets in vitro and in vivo. Silencing of HIF1α attenuates inhibition of neddylation-induced glycolytic rates in cardiomyocytes. Taken together, our findings highlight the importance of neddylation in the developing heart and identify neddylation as a novel regulator of HIF1α signaling to promote developmental metabolic switch.
Chidamide-Containing Conditioning Allogenic Hematopoietic Stem Cell Transplantation Improves Prognosis of Acute Lymphoblastic Leukemia with Pre-Transplant Response Less Than Complete Remission
Authors: Jie Ji, Tian Dong, Pu Kuang, Zhigang Liu, Jiazhuo Liu, Li Zhang, Ting Niu, Ting Liu
Journal: Blood (2018)
Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial
Authors: Yunpeng Yang, Jianya Zhou, Jianying Zhou, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Yunpeng Liu, Zhendong Zheng, Gaofeng Li, Ning Wu, Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Li Mao, Giovanni Selvaggi, Xiaobin Yuan, Yuanqing Fu, Tao Wang, Shanshan Xiao, Li Zhang
Journal: The Lancet Respiratory Medicine (2019)
Myocardial Ultrastructure in Idiopathic Hypertrophic Subaortic Stenosis
Authors: VICTOR J. FERRANS, ANDREW G. MORROW, WILLIAM C. ROBERTS
Journal: Circulation (1972)

Electron microscopic studies revealed distinctive abnormalities in operatively resected myocardium from the left ventricular outflow tract in 14 patients with idiopathic hypertrophic subaortic stenosis. Bundles of muscle cells were severely disorganized, with cells running in different directions instead of in parallel. Muscle cells were wider and shorter than in hypertrophy due to other causes and showed increased cellular branching, extensive side-to-side intercellular junctions, widened Z bands, and evidence of formation of new sarcomeres. Some myofibrils were oriented obliquely or perpendicular to the longitudinal axes of the cells and some myofilaments that originated from a single Z band inserted into Z bands of other myofibrils. Examination of left ventricular apical myocardium in two patients revealed hypertrophied but normally arranged muscle cells. It is concluded that abnormal architecture of muscle cells is the basic morphologic feature of idiopathic hypertrophic subaortic stenosis.
Bfr (bendamustine, fludarabine, rituximab) Vs. FCR Nonmyeloablative Allogeneic Conditioning In Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL): Outcome Results Including Minimal Residual Disease Analysis
Authors: Issa F. Khouri, Rima M. Saliba, Pramoda Challagundla, Celina Ledesma, Martin Korbling, Alison M Gulbis, Maria Guillermo-Pacheco, Sairah Ahmed, Paolo Anderlini, Qaiser Bashir, Betul Oran, Stefan O Ciurea, Chitra M. Hosing, Partow Kebriaei, Uday R Popat, Elias Jabbour, Richard E Champlin, Jeffrey L. Jorgensen
Journal: Blood (2013)
Inhibition of B-NHL Tumor Xenografts Following Treatment with Galiximab (Anti-CD80 mAb) and Potentiation When Combined with Chemotherapy
Authors: Mario I Vega, Hari Hariharan, Peter Chu, Tracey Murphy, Dana Clanton, Lisa Berquist, Arturo Molina, Steffan Ho, Benjamin Bonavida
Journal: Blood (2012)
The study on functions and mechanisms of miR-106b in the metastasis of colorectal cancer.
Authors: Shujuan Ni, Qifeng WANG, Cong Tan, Xiang Du
Journal: Journal of Clinical Oncology (2013)

e14685 Background: Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour initiation, development and progression. However, little is known about the potential role of miRNAs in colorectal cancer (CRC) metastasis. Methods: The miR-106b expression levels in CRC tissues were deteted by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to investigate its relationship with clinical characteristics or survival of CRC patients. Using the CRC cell lines ectopically expressing miR-106b conducted by lentivirus transduction as experimental material, cell culture, cell growth analysis and transwell used to analyze the potential influence of miR-106b on CRC metastasis. In addition, luciferase assays and western blot were used for the target gene study. Results: In this study, we firstly investigate the role and related mechanism of miR-106b in CRC metastasis. We found that miR-106b expression was lower than in CRC compared with their corresponding non-tumorous tissues (P=0.009), and the downregulated miR-106b was negatively associated with lymph-node metastasis. Functional assays demonstrated that overexpression of miR-106b suppressed CRC cell migration and invasion in vitro. In addition, we confirmed that ATAD2 was a direct and functional target of miR-106b. Overexpression of miR-106b in CRC cells could reduce the mRNA and protein levels of ATAD2, whereas miR-106b silencing significantly increased ATAD2 expression. Luciferase assays confirmed that miR-106b could directly bind to 3′ untranslated region of ATAD2. Knockdown of ATAD2 significantly inhibited CRC cell migration and invasion. We further found that ATAD2 was involved in miR-106b-induced suppression of CRC cell migration and invasion. Conclusions: By understanding the functions and molecular mechanisms of miR-106b in CRC, we found mir-106b through targeting ATAD2 inhibited CRC cell migration and invasion. These results suggest that patients with downregulated miR-106b are prone to lymph node metastasis and tumour progression. miR-106b may have a therapeutic potential to suppress CRC metastasis.