tbuckley/cabot-search huggingface dataset:
Abstract 17326: Clues to Attenuating Plaque Inflammation: Heat Shock Protein-27 Augments Macrophage Histone Deacetylase-6 Activity and Cytoskeletal Migratory Capacity
Authors: Gérémy A Koumbadinga, Daiana Alvarez-Omeldo, Edward R O’Brien
Journal: Circulation (2015)

Introduction: We recently demonstrated that elevated serum levels of Heat Shock Protein 27 (HSP27) are associated with reduced 5-year CV events and that extracellular HSP27 attenuates experimental atherogenesis and lesion progression. Indeed, HSP27 therapy reduces plaque macrophage and cholesterol content and enhances histological features associated with resilience to plaque rupture. Cell motility and adhesion involves dynamic microtubule acetylation/deacetylation, a process regulated by the enzyme histone deacetylase 6 (HDAC6), a major cytoplasmic α-tubulin deacetylase. We hypothesize that HSP27 enhances HDAC6 activity to promote favorable plaque remodeling by enhancing macrophage migration. Methods / Results: 1. The HDAC6 activity of THP-1 macrophages treated with recombinant HSP27 was assessed using a fluorescent plate reader ELISA. In a dose-dependent fashion, rHSP27 treatment resulted in a 100% increase in HDAC-6 activity compared to the control and was independent of HSP27 phosphorylation. Moreover, HDAC-6 activity was enhanced 100% in peritoneal macrophages harvested from rHsp27-treated ApoE-/- vs. control mice. With the addition of cycloheximide HDAC-6 activity was not prolonged, suggesting that HSP27 did not have an effect on the enzymatic half-life. 2. When HSP27 expression was knocked down in THP-1 cells transfected with a lentivirus carrying specific shRNA-HSP27 vector there was a reduction in HDAC6 activity and an increase in tubulin acetylation - and both of these effects were rescued with the addition of rHSP27. 3. Using a Boyden chamber cell migration assay, we found that rHSP27 treatment increased migration of THP-1 cells without and with ox-LDL loading by ~2- and ~1.5-fold; respectively - an effect that was blocked by either Tubacin (a specific inhibitor of HDAC6) or HSP27 knockdown. Conclusion: Extracellular HSP27 is capable of up-regulating HDAC6 activity in macrophages, an effect associated with enhanced macrophage migratory capacity. These data suggest that HSP27 may be important for potentially improving macrophage egress from plaques thereby resulting in reduced cholesterol content and more stable lesions - factors that may explain the proven predictive biomarker value of elevated serum HSP27 levels.
Dexamethasone Without Antibiotics for Sore Throat
Authors: David O. Francis, Albert L. Merati
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
フィーダ誘導マトリックスによるマウス胚性幹細胞の運命とゲノム完全性の生物物理学的制御【Powered by NICT】
Authors: Sthanam Lakshmi Kavitha, Barai Amlan, Rastogi Anuj, K Mistari Vijay, Maria Ana, Kauthale Rahul, Gatne Madhumanjiri, Sen Shamik
Journal: Biomaterials (2017)
Trunk mutational events present minimal intra- and inter-tumoral heterogeneity in hepatocellular carcinoma
Authors: Sara Torrecilla, Daniela Sia, Andrew N. Harrington, Zhongyang Zhang, Laia Cabellos, Helena Cornella, Agrin Moeini, Genis Camprecios, Wei-Qiang Leow, Maria Isabel Fiel, Ke Hao, Laia Bassaganyas, Milind Mahajan, Swan N. Thung, Augusto Villanueva, Sander Florman, Myron E. Schwartz, Josep M. Llovet
Journal: Journal of Hepatology (2017)
蛋白質コロナの制限:抗HER2ナノボディ官能化ナノスターのin vivoでの活性標的化のための成功戦略【Powered by NICT】
Authors: D’Hollander Antoine, Jans Hilde, Velde Greetje Vande, Verstraete Charlotte, Massa Sam, Devoogdt Nick, Stakenborg Tim, Muyldermans Serge, Lagae Liesbet, Himmelreich Uwe
Journal: Biomaterials (2017)
Combination Cancer Therapy Using Chimeric Antigen Receptor-Engineered Natural Killer Cells as Drug Carriers
Authors: Elizabeth L. Siegler, Yu Jeong Kim, Xianhui Chen, Natnaree Siriwon, John Mac, Jennifer A. Rohrs, Paul D. Bryson, Pin Wang
Journal: Molecular Therapy (2017)

The therapeutic limitations of conventional chemotherapeutic drugs include chemo-resistance, tumor recurrence, and metastasis. Numerous nanoparticle-based active targeting approaches have emerged to enhance the intracellular concentration of drugs in tumor cells; however, efficient delivery of these systems to the tumor site while sparing healthy tissue remains elusive. Recently, much attention has been given to human immune-cell-directed nanoparticle drug delivery, because immune cells can traffic to the tumor and inflammatory sites. Natural killer cells are a subset of cytotoxic lymphocytes that play critical roles in cancer immunosurveillance. Engineering of the human natural killer cell line, NK92, to express chimeric antigen receptors to redirect their antitumor specificity has shown significant promise. We demonstrate that the efficacy of chemotherapy can be enhanced in vitro and in vivo while reducing off-target toxicity by using chimeric antigen receptor-engineered NK92 cells as carriers to direct drug-loaded nanoparticles to the target site.
多剤耐性乳癌と戦うためのpH応答性配位結合に基づくトランスフェリンに触発された車両【Powered by NICT】
Authors: He Yu-Jing, Xing Lei, Cui Peng-Fei, Zhang Jia-Liang, Zhu Yong, Qiao Jian-Bin, Lyu Jin-Yuan, Zhang Mei, Luo Cheng-Qiong, Zhou Yu-Xin, Lu Na, Jiang Hu-Lin
Journal: Biomaterials (2017)
Evaluation of HCC response to locoregional therapy: Validation of MRI-based response criteria versus explant pathology
Authors: Sonja Gordic, Idoia Corcuera-Solano, Ashley Stueck, Cecilia Besa, Pamela Argiriadi, Preethi Guniganti, Michael King, Shingo Kihira, James Babb, Swan Thung, Bachir Taouli
Journal: Journal of Hepatology (2017)
Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity
Authors: Lawrence Kazak, Edward T. Chouchani, Gina Z. Lu, Mark P. Jedrychowski, Curtis J. Bare, Amir I. Mina, Manju Kumari, Song Zhang, Ivan Vuckovic, Dina Laznik-Bogoslavski, Petras Dzeja, Alexander S. Banks, Evan D. Rosen, Bruce M. Spiegelman
Journal: Cell Metabolism (2017)
Abstract 213: Rapid Activation of G-Protein Coupled Estrogen Receptor 1 Protects the Heart Against Ischemia-Reperfusion Injury by Inhibiting the mPTP Opening via PKC/AKT/ERK/GSK-3b Pathways
Authors: Jean Chrisostome Bopassa, Rong Lu, Harpreet Singh, Netanel F Zilberstein, Bjorn Olde, Andree Krust, L M Fredrik Leeb-Lundberg, Ligia Toro, Enrico Stefani
Journal: Circulation Research (2012)

Introduction: Estrogen effect can be mediated by three receptors: Classical estrogen receptors: alpha (ERa) and beta (ERb), and recently identified G protein-coupled estrogen receptor1 (GPER1). Hypothesis: We investigated the role of ERa, ERb and GPER1 in mediating rapid estrogen-induced cardioprotection in male mice hearts subjected to ischemia/reperfusion using wild type (WT) and gene specific knockout animals. Methods: Isolated hearts from wild type (WT: C57BL/6NCrL), ERa-/-, ERb-/- and GPER1-/- were perfused using Langendorff apparatus with Krebs Henseleit buffer (control) or with the addition of estrogen (40 nM). Hearts were subjected to 18 min global ischemia followed by 60 min reperfusion. Cardiac function was recorded during the entire experiment and myocardial infarct size measured by TTC staining at the end of the reperfusion. Mitochondria calcium retention capacity (CRC) required to induce the mitochondrial permeability transition pore (mPTP) opening was assessed after 10 min reperfusion. Protein levels were measured by Western Blot in whole heart lysates after 5 min treatment just before ischemia, and after 10 min reperfusion. LY294002, U0126 and Chelerythrin-Cl were used as inhibitor of PI-3K/Akt, MAPK/ERK and PKC translocation, respectively. Results: In WT, ERa-/- and ERb-/-, estrogen treatment significantly improved cardiac functional recovery, reduced infarct size and improved mitochondrial CRC. However, estrogen effects were completely absent in GPER1-/-. Estrogen treatment during 5 min before ischemia induced up-regulation of Akt, GSK-3b, and ERK1/2 phosphorylation in WT mouse as compared with control but not in GPER1-/-. However, after 10 min reperfusion estrogen effect was still oserved on GSK-3b, but not on Akt and ERK1/2. Chelerythrin-Cl prevented estrogen-induced cardioprotection effect and U126 abolished estrogen effect on mitochondrial CRC while LY294002 could not prevent estrogen effect on GSK-3b observed in WT. P&lt;0.05 and n=3-6. Conclusion: Rapid activation of GPER1 induces cardioprotection effect against ischemia/reperfusion injury. Estrogen effects through GPER1 are associated with phosphorylation of Akt, GSK-3b and ERK1/2, translocation of PKC, and inhibition of the mPTP opening.
Relationship Between Treatment-Induced Changes in Left Ventricular Mass and Blood Pressure in Black African Hypertensive Patients
Authors: Daniel Skudicky, Pinhas Sareli, Elena Libhaber, Geoffrey Candy, Ivo Radevski, Zdravska Valtchanova, Elizabeth Tshele, Lutgarde Thijs, Ji-Guang Wang, Jan A. Staessen
Journal: Circulation (2002)

Background — In a single-center study, we compared to what extent changes in conventional and ambulatory blood pressure (BP) predicted regression of left ventricular mass (LVM) index in response to antihypertensive treatment in previously untreated and treated patients with sustained hypertension. Methods and Results — We enrolled 173 black African patients who, off treatment, had a daytime diastolic BP ranging from 90 to 114 mm Hg. Antihypertensive drugs were titrated and combined to reduce the daytime diastolic BP below 90 mm Hg. Echocardiograms were obtained at baseline and follow-up. Mean systolic/diastolic clinic BP, 24-hour BP, and LVM index were similar in previously untreated (n=64) and previously treated (n=109) patients and averaged 171/102 mm Hg, 151/97 mm Hg, and 118 g/m 2 , respectively. At 4 months, these values had decreased ( P &lt;0.001) by 26/12 mm Hg, 23/14 mm Hg, and 14 g/m 2 in previously untreated patients and by 22/9 mm Hg, 21/13 mm Hg, and 19 g/m 2 in previously treated patients. In the previously untreated patients, the regression in LVM index correlated to a similar degree ( P =0.09) with the decreases in the conventional ( r =0.34; P =0.005) and the 24-hour ( r =0.26; P =0.04) systolic BP. In the previously treated patients, the corresponding correlations were 0.02 ( P =0.82) and −0.10 ( P =0.32), respectively. Compared with the 24-hour systolic BP, automated oscillometric measurements of systolic BP obtained at the clinic yielded similar results. Conclusions — In previously untreated patients with sustained hypertension followed at a single center, reductions in clinic and ambulatory systolic pressure in response to antihypertensive treatment equally predicted the regression in LVM index.
Lessons From an Educational Never Event
Authors: Catherine R. Lucey, Renee Navarro, Talmadge E. King
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
AB0218 Correlation of gray scale and power doppler ultrasonography with clinical evaluation in rheumatoid arthritis
Authors: IE Okatan, M Torgutalp, ME Yayla, AB Dinçer Keleşoğlu, E Uslu Yurteri, A Ateş, TM Turgay, G Kınıklı
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Ultrasonography (US) is a useful method for assessing synovial vascularization and proliferation in rheumatoid arthritis (RA). The aim of the study is to compare the tender joint and swollen joint in patients with rheumatoid arthritis (RA) with gray scale (GS) and power doppler (PD) ultrasonography (US). <h3>Methods</h3> Thirty RA patients were included. Median disease duration was 53.7 months. Demographic and clinical data, C reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) were recorded for each patient. Disease activity was evaluated using the Disease Activity Score in 28-joints (DAS28) with a median score 3.8.The joint tenderness and swelling were assessed for 10 joints (wrists, second and third proximal interphalangeal and metacarpophalangeal) in each patient.These joints were evaluated by GS and PD by ultrasonography. US joint effusion, synovitis and PD signals were graded from 1 to 3 for each joints. The 10-joint GS and 10-joint PD scores were then calculated. Correlations were tested using the Spearman coefficient. <h3>Results</h3> GS effusion, synovitis scores (r =0.565, p&lt;0.001) and PD signals (r =0.883, p&lt;0.001) correlated highly with the corresponding swollen joints. There was a significant correlation between DAS28 and number of tender joints (r=0.745, p&lt;0.001) but no correlation was found between the tender joints and ultrasonographycal effusion, synovitis grade (r=0.073, p&gt;0.001) and the PD signal (r=0.069, p&gt;0.001). There was moderate correlation between 10 joints GS, 10 joints PD and DAS28, but it was not statistically significant. <h3>Conclusions</h3> Evaluating the swollen joints with clinical examination and combining it with US is a sensitive method. As joint tenderness is a more subjective finding than the joint swelling, this may explain the lack of correlation between tender joints and ultrasonography findings. We suggest to use Gray scale US and PD as a complementary method in addition to clinical assessment of joint tenderness in patients with RA. <h3>Disclosure of Interest</h3> None declared
ポリカチオン核酸キャリアの安定性とカーゴ放出のジレンマを解決するためのスイッチ可能な重合体の開発【Powered by NICT】
Authors: Cheng Yilong, L Sellers Drew, Y Tan James-Kevin, J Peeler David, J Horner Philip, H Pun Suzie
Journal: Biomaterials (2017)
IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite–induced asthma models
Authors: Takashi Ito, Koichi Hirose, Aiko Saku, Kenta Kono, Hiroaki Takatori, Tomohiro Tamachi, Yoshiyuki Goto, Jean-Christophe Renauld, Hiroshi Kiyono, Hiroshi Nakajima
Journal: The Journal of Experimental Medicine (2017)

Previous studies have shown that IL-22, one of the Th17 cell–related cytokines, plays multiple roles in regulating allergic airway inflammation caused by antigen-specific Th2 cells; however, the underlying mechanism remains unclear. Here, we show that allergic airway inflammation and Th2 and Th17 cytokine production upon intratracheal administration of house dust mite (HDM) extract, a representative allergen, were exacerbated in IL-22-deficient mice. We also found that IL-22 induces Reg3γ production from lung epithelial cells through STAT3 activation and that neutralization of Reg3γ significantly exacerbates HDM-induced eosinophilic airway inflammation and Th2 cytokine induction. Moreover, exostatin-like 3 (EXTL3), a functional Reg3γ binding protein, is expressed in lung epithelial cells, and intratracheal administration of recombinant Reg3γ suppresses HDM-induced thymic stromal lymphopoietin and IL-33 expression and accumulation of type 2 innate lymphoid cells in the lung. Collectively, these results suggest that IL-22 induces Reg3γ production from lung epithelial cells and inhibits the development of HDM-induced allergic airway inflammation, possibly by inhibiting cytokine production from lung epithelial cells.
miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways
Authors: Giulio Ceolotto, Alessandra Giannella, Mattia Albiero, Maniselvan Kuppusamy, Claudia Radu, Paolo Simioni, Katia Garlaschelli, Andrea Baragetti, Alberico Luigi Catapano, Elisabetta Iori, Gian Paolo Fadini, Angelo Avogaro, Saula Vigili de Kreutzenberg
Journal: Cardiovascular Research (2017)

Atherosclerosis is an inflammatory disease wherein cholesterol-loaded macrophages play a major role. MicroRNAs and microparticles propagate inflammatory pathways and are involved in cardiovascular disease. We aimed to screen and validate circulating microRNAs correlated with atherosclerosis development in humans, and to dissect the molecular mechanisms associated with atherogenesis using in vitro and in vivo approaches.A panel of 179 secreted microRNAs was screened in plasma samples of patients with and without atherosclerosis, and validated cross-sectionally and prospectively in patients followed for up to 11 years. miR-30c-5p was inversely correlated with total and LDL cholesterol, carotid intimal media thickness (CIMT), presence and future development of plaques. Using a human macrophage line and in vitro gene silencing strategies, we found that miR-30c-5p was downregulated by oxidized LDL (oxLDL) via the scavenger receptor CD36 and inhibition miR processing by Dicer. In turn, miR-30c-5p downregulation was responsible for the effects of oxLDL on macrophage IL-1β release, caspase-3 expression, and apoptosis. miR-30c-5p loaded into microparticles was uptaken by macrophages and regulated target genes, like caspase-3, at transcriptional level. To establish the relevance of this pathway on endothelial damage as the earliest step of atherogenesis, we show that systemic miR-30c-5p knockdown induced caspase-3 and impaired endothelial healing after carotid injury in C57Bl/6 J mice.With an unbiased screening of secreted microRNAs, we identify reduction of miR-30c-5p in microparticles as a promoter of early atherosclerosis, by conveying pro-inflammatory pro-apoptotic signals and impairing endothelial healing. Therefore, stimulation of miR-30c-5p is a candidate direct anti-atherosclerotic therapy.
Can the performance of a quantitative FIT-based colorectal cancer screening programme be enhanced by lowering the threshold and increasing the interval?
Authors: Jayne Digby, Callum G Fraser, Frank A Carey, Robert J C Steele
Journal: Gut (2017)

We read with interest the work by Haug et al published in Gut .1 Longitudinal data from 4523 participants in the first round of a faecal immunochemical test for haemoglobin (FIT)-based screening programme, of whom 3427 also participated in the second round, were studied. In both first and second rounds, a threshold of 10 µg Hb/g faeces was used. The cohort was followed up for 2 years. The cumulative positivity and the number of participants diagnosed with neoplasia over the two rounds of screening were determined and compared with a hypothetical strategy involving single round screening with use of lower faecal haemoglobin concentration (f-Hb) thresholds and omission of the second round. It was suggested that lowering the f-Hb threshold and extending the screening interval could possibly enhance population-based screening programmes.

In our pilot evaluation of FIT-based screening in Scotland, a much higher f-Hb threshold (≥80 µg Hb/g faeces) was employed.2 …
Outcomes Associated With Extraction Versus Capping and Abandoning Pacing and Defibrillator Leads
Authors: Sean D. Pokorney, Xiaojuan Mi, Robert K. Lewis, Melissa Greiner, Laurence M. Epstein, Roger G. Carrillo, Emily P. Zeitler, Sana M. Al-Khatib, Donald D. Hegland, Jonathan P. Piccini
Journal: Circulation (2017)

Background: Lead management is an increasingly important aspect of care in patients with cardiac implantable electronic devices; however, relatively little is known about long-term outcomes after capping and abandoning leads. Methods: Using the 5% Medicare sample, we identified patients with de novo cardiac implantable electronic device implantations between January 1, 2000, and December 31, 2013, and with a subsequent lead addition or extraction ≥12 months after the de novo implantation. Patients who underwent extraction for infection were excluded. Using multivariable Cox proportional hazards models, we compared cumulative incidence of all-cause mortality, device-related infection, device revision, and lead extraction at 1 and 5 years for the extraction versus the cap and abandon group. Results: Among 6859 patients, 1113 (16.2%) underwent extraction, whereas 5746 (83.8%) underwent capping and abandonment. Extraction patients tended to be younger (median, 78 versus 79 years; P &lt;0.0001), were less likely to be male (65% versus 68%; P =0.05), and had shorter lead dwell time (median, 3.0 versus 4.0 years; P &lt;0.0001) and fewer comorbidities. Over a median follow-up of 2.4 years (25th, 75th percentiles, 1.0, 4.3 years), the overall 1-year and 5-year cumulative incidence of mortality was 13.5% (95% confidence interval [CI], 12.7–14.4) and 54.3% (95% CI, 52.8–55.8), respectively. Extraction was associated with a lower risk of device infection at 5 years relative to capping (adjusted hazard ratio, 0.78; 95% CI, 0.62–0.97; P =0.027). There was no association between extraction and mortality, lead revision, or lead extraction at 5 years. Conclusions: Elective lead extraction for noninfectious indications had similar long-term survival to that for capping and abandoning leads in a Medicare population. However, extraction was associated with lower risk of device infections at 5 years.
凍結保存された生微粉化羊膜の局所投与は局所的な微小環境を調節することにより糖尿病マウスの創傷治癒を促進する【Powered by NICT】
Authors: Zheng Yongjun, Ji Shizhao, Wu Haibin, Tian Song, Zhang Yunqing, Wang Li, Fang He, Luo Pengfei, Wang Xingtong, Hu Xiaoyan, Xiao Shichu, Xia Zhaofan
Journal: Biomaterials (2017)
Youth of today is the future of tomorrow
Authors: Justin Carrard, Boris Gojanovic
Journal: British Journal of Sports Medicine (2017)

The future of Sports and Exercise Medicine (SEM), a young medical discipline, rests heavily on the involvement and commitment of the current generation of medical students. SEM is a fully recognised specialty on a handful of countries, something that is not mirrored in the majority of regions worldwide,1 and SEM will not form any meaningful part of the medical curriculum in universities in most countries.2 3 This exclusion from the academic process results in limited awareness among students and physicians about what SEM actually involves. SEM’s role in the fight against the burden of non-communicable diseases is simply ignored or misunderstood at best.4 If we, as SEM practitioners, are to stand a chance of harnessing the medical potential of SEM, we need to acknowledge the importance of grassroots development, that is, …