tbuckley/cabot-search huggingface dataset:
Abstract 329: N-acetylcyteine Alleviate Inflammasome-Induced Myocardial Pyroptosis After Successful Resuscitation in a Rat Model of Cardiac Arrest
Authors: Fenglian He
Journal: Circulation (2018)

Introduction: Previous studies have demonstrated that pyroptosis is involved in myocardial ischemia/reperfusion injury (MIRI). In addition, N-acetylcyteine (NAC) can attenuate inflammasome-induced pyroptosis during regional MIRI. In the present study, we investigated whether pyroptosis participate in global MIRI after successful resuscitation, and if it does, whether NAC can reduce inflammasome-induced pyroptosis in a rat model of cardiac arrest and resuscitation. Hypothesis: N-acetylcyteine reduces inflammasome-induced myocardial pyroptosis after successful resuscitation in a rat model of cardiac arrest. Methods: Fifteen male rats weighing 450g-550g were randomized into three groups: sham group, control group and NAC group (150 mg/kg). Ventricular fibrillation (VF) was electrically induced and untreated for 8 min. After VF, CPR was initiated for 8 mins and then defibrillation was attempted. Animals in sham group only were underwent the same operation but without inducing CA. The expressions of Nod-like receptor protein3 (NLRP3), adaptor apoptosis-associated speck-like protein (ASC), caspase-1 and gasdermin D (GSDMD) proteins were detected by western blotting at 6h following successful resuscitation. Results: All animals were resuscitated. Significantly higher levels expressions of GSDMD, NLRP3, ASC and caspase-1 were observed in control group and NAC group when compared with sham group. However, the expressions in GSDMD, NLRP3, ASC and caspase-1 were downregulated in NAC group in comparison with the control group. (Figure) Conclusion: N-acetylcyteine attenuate inflammasome-induced myocardial pyroptosis after successful resuscitation in a rat model of cardiac arrest. Figure Expressions of GSDMD, NLRP3, ASC and caspase-1 proteins, and effect of NAC on cardiac pyroptosis after successful resuscitation in a rat model of CA. (A) Representative western blotting images of GSDMD, NLRP3, ASC and caspase1 proteins in the hearts at 6h after successfully resuscitated (B) Quantitative protein analysis of GSDMD, NLRP3, ASC and caspase1 expression in three groups. The columns represent means ± SEM of three independent experiments. * p &lt; .05
Abstract PO-087: Novel high-throughput screen in a breast cancer cell line to identify potent radiosensitizers
Authors: Madeleine R. Landry, Allison N. DuRoss, Eunseo Choi, Antony Jozic, Dylan Nelson, Conroy Sun
Journal: Clinical Cancer Research (2021)

Abstract There is a need for more broadly applicable radiosensitizers independent of disease state and DNA protein repair status. High throughput screens hold potential for identifying new classes of radiosensitizers from libraries of small molecules. Our group has developed an in vitro high throughput screen identifying radiosensitizers using high content imaging. Due to chromatin condensation, G2/M is acknowledged as the most radiosensitive phase of the cell cycle. We therefore dosed 4T1 breast cancer cells with a library of 1430 FDA approved drugs, then using the high content images, assessed ability to stall in G2/M. We initially eliminated drugs with less than 30% viability from consideration to negate toxicity effects on the CCI. With a CCI cutoff of two standard deviations from the mean, we attained a hit rate of 2.8% with 40 hits. The screen identified both known and novel radiosensitizers belonging to previously unidentified classes. This methodology of cell cycle analysis was confirmed by the more classical flow cytometry assay and a selected hit from the screen was assessed for radiosensitizing ability by clonogenic and γH2AX assays, and in vivo studies. Based on the clonogenic survival fractions, the radiation enhancement ratio was found to be &amp;gt;1 at all doses between 2-6 Gy for the selected drug, with the highest values at 4 and 5 Gy of 4.5. Furthermore, we found two 10 µM doses of the novel radiosensitizer paired with two fractions of 2 Gy was sufficient to significantly decrease 4T1 tumor volume growth in BALB/c mice. Citation Format: Madeleine R. Landry, Allison N. DuRoss, Eunseo Choi, Antony Jozic, Dylan Nelson, Conroy Sun. Novel high-throughput screen in a breast cancer cell line to identify potent radiosensitizers [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-087.
Differential modulation of cyclooxygenase (COX) enzymes by the two putative cancer chemopreventive flavones apigenin and tricin
Authors: Mohammad A. Al-Fayez, Hong Cai, Richard G. Tunstall, William P. Steward, Andreas G. Gescher
Journal: Cancer Research (2006)

3183  The safety concerns which cast doubt on the prudence of using synthetic COX-2 inhibitors as cancer chemopreventive agents have invigorated the search for novel chemopreventive agents from the plant kingdom. Tricin (4’,5,7-trihydroxy-3’,5’-dimethoxyflavone) contained in grass species and apigenin (4’,5,7-trihydroxyflavone) from leafy vegetables are congeneric flavones with putative cancer chemopreventive properties, which are thought to engage mechanisms targeted at COX enzymes. Here the hypothesis was tested that COX activity and levels are affected by tricin and apigenin in a similar fashion. Experiments were conducted with both flavones in three different systems: i) to explore their effect on COX activity they were incubated with purified COX-1 and COX-2 enzymes from sheep seminal vesicles and placenta, respectively, in a cell free-system; activity was assessed using a commercially available chemiluminescent enzyme activity kit, which measures COX peroxidase function. ii) Their ability to interfere with inducible COX-2 expression in intact cells was studied in human colon-derived epithelial HCEC cells; enzyme expression was induced by phorbol myristoyl acetate, after which cells were exposed to the flavones for 6 or 24 h. iii) Their effect on inducible prostaglandin E-2 (PGE-2) levels was assessed by competitive immunoassay in HCEC cells. Tricin inhibited COX-1 and COX-2 activity in the cell-free system similarly with an IC50 of ∼1 μM, whilst apigenin up to 25 μM did not affect enzyme activity. Tricin decreased inducible COX-2 protein expression significantly; densitometry readings showed that after 24 h incubation 10 μM tricin decreased COX-2 protein by 48±16% (mean±ΣΔ, ν=3) compared to control. Apigenin reduced COX-2 levels after incubation with cells for 6 h in a concentration-dependent fashion, at 20 μM by 55±13% (mean±SD, n=3) compared to control. In contrast, exposure of cells for 24 h to apigenin increased COX-2 expression, at 20 μM by 2.1 fold over control. Both tricin and apigenin decreased PGE-2 generation in HCEC cells. After 24 h incubation with 20 μM flavone, tricin reduced PGE-2 by 52±10% (mean±SD, n=5) compared to cells unexposed to flavone, whilst apigenin abolished measurable PGE-2 almost completely. These results show that tricin and apigenin regulate COX-enzymes in different ways, tricin being a potent COX inhibitor in vitro, whilst apigenin, which was devoid of enzyme-inhibitory properties, reduced cellular PGE-2 levels more strongly than tricin.
SOCIAL DETERMINANTS OF HEALTH DISPARITIES FOR COVID-19 MITIGATION MEASURES AMONG ADULTS WITH CARDIOVASCULAR DISEASE IN UNITED STATES
Authors: Kobina Hagan, Zulqarnain Javed, Javier Valero-Elizondo, Safi Khan, Tamer Yahya, Isaac Acquah, Farhaan S. Vahidy, Melina Awar, Prachi Dubey, Bita Kash, Dirk H. Sostman, Miguel Cainzos-Achirica, Khurram Nasir
Journal: Journal of the American College of Cardiology (2021)
Invasive Mucinous Adenocarcinomas With Spatially Separate Lung Lesions: Analysis of Clonal Relationship by Comparative Molecular Profiling
Authors: Soo-Ryum Yang, Jason C. Chang, Charles Leduc, Kay See Tan, Snjezana Dogan, Ryma Benayed, Laetitia Borsu, Michael Offin, Alexander Drilon, William D. Travis, Maria E. Arcila, Marc Ladanyi, Natasha Rekhtman
Journal: Journal of Thoracic Oncology (2021)
Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis
Authors: Geraldine J. Ooi, Peter J. Meikle, Kevin Huynh, Arul Earnest, Stuart K. Roberts, William Kemp, Benjamin L. Parker, Wendy Brown, Paul Burton, Matthew J. Watt
Journal: Journal of Hepatology (2021)
Abstract 15313: Analysis of Survival in Octogenarian and Nonagenarian Patients Treated With Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction
Authors: Aaruni Saxena, Hedra Ghobrial, Ahmed Sayed G AlSayed Ahmed, Shahnaz Jamil-Copley, Nikola Sprigg, Akhlaque Uddin
Journal: Circulation (2020)

Introduction: With advancement in interventional cardiology an increase in the number of percutaneous coronary intervention (PCI) procedures has been noted in the elderly. However, the post procedure complication and mortality remain a challenge for the physicians. This study aimed to estimate the survival among men and women above 80 years of age who undergo primary PCI for treatment of ST elevation myocardial infarction. Methods: We analyzed the data collected prospectively from our cardiac center. The patients were followed up over 10 years. Most patient received stents followed by anti-platelet drugs and preventive measures to avoid further cardiac event. Kaplan Meier curves were generated to study survival post PCI (SPSS v2.2). Survival curves were developed to determine the influence of age, sex, type of stent and degree of coronary flow (TIMI 0-3) on post procedure survival. Results: From 2010 to 2019, total 502 patients &gt;80 years received PCI (282 males, 218 females). The median survival in the male and female population were 2.16 yrs. (95% CI 1.66 - 2.66) and 2.36 yrs. (95% CI 1.72-2.99)(P= 0.18). Significant difference of around 1 year (2.7 yrs. octogenarian vs 1.6 yrs. nonagenarian, p&lt;0.001, see figure 1) was found in post PCI survival between octogenarian and nonagenarian. However, the survival was longer in case of Bare metal stents (BMS)(n= 113) as compared to Drug eluting stents(DES)(n= 274) (2.7 yrs. vs. 2.0yr, p&lt;0.001). Similarly, post procedure TIMI flow analysis shows maximum survival in TIMI 3 followed by TIMI 2 and TIMI 1 ensuring the significance of TIMI grade flow. Conclusions: Our results demonstrate that PPCI in elderly patients have a better outcome and longer survival in octogenarians than nonagenarians. Similarly, use of BMS could be considered over DES in population above 80 years of age irrespective of gender. No difference in post PCI survival in male and female population.
A protocol for rapid isolation of intracellular and extracellular proteins from whole tissue
Authors: Mitra Azadeh, Tao Li, Maribeth A. Raines, Kevin J. Reagan
Journal: Cancer Research (2005)

4569  Primary tissues are valuable tools for the study of intracellular and extracellular markers which characterize disease states. For example, the clinical progression of many tumors is assessed by monitoring tumor necrosis factor alpha (TNF-α) levels in malignant tissues. We have developed a protocol for rapid isolation of cytokines and signaling molecules from intact tissue. This method is for total protein extraction and makes use of a non-abrasive tissue extraction reagent. Tissue samples as little as ten milligrams may be extracted with this protocol, rendering this a convenient method for the analysis of biopsy samples from solid tumors. To test this system, we prepared tissue extracts from both healthy and diseased mouse organs. Using immunoassays specific for each marker, these extracts were then compared for the levels of cytokines, vascular endothelial growth factor (VEGF), TNF-α, and IL-12 and intracellular signaling markers, ERK1/2, p38, JNK1/2, AKT, and FAK. Results from immunoassays demonstrate that the method is sensitive and allows for the detection of disease-associated fluctuations in the tissue levels of these metastatic biomarkers. This is an effective system for the extraction of proteins from all tissue types; heart, lung, kidney, spleen, brain, liver, thymus, and smooth muscle tissues have all been successfully extracted with this protocol. The prepared extracts are shown to be compatible with a variety of immunoassays, as well as with all conventional protein assays. The compatibility of these tissue extracts with protein kinase assays and immunoprecipitation protocols is currently under investigation. Our tissue extraction method is inexpensive, versatile, and can be completed in less than fifteen minutes.
A free-form patterning method enabling endothelialization under dynamic flow
Authors: Xi Wu, Silvia Moimas, Raoul Hopf, Costanza Giampietro, Andreas Kourouklis, Volkmar Falk, Edoardo Mazza, Aldo Ferrari
Journal: Biomaterials (2021)

Endothelialization strategies aim at protecting the surface of cardiovascular devices upon their interaction with blood by the generation and maintenance of a mature monolayer of endothelial cells. Rational engineering of the surface micro-topography at the luminal interface provides a powerful access point to support the survival of a living endothelium under the challenging hemodynamic conditions created by the implant deployment and function. Surface structuring protocols must however be adapted to the complex, non-planar architecture of the target device precluding the use of standard lithographic approaches. Here, a novel patterning method, harnessing the condensation and evaporation of water droplets on a curing liquid elastomer, is developed to introduce arrays of microscale wells on the surface of a biocompatible silicon layer. The resulting topographies support the in vitro generation of mature human endothelia and their maintenance under dynamic changes of flow direction or magnitude, greatly outperforming identical, but flat substrates. The structuring approach is additionally demonstrated on non-planar interfaces yielding comparable topographies. The intrinsically free-form patterning is therefore compatible with a complete and stable endothelialization of complex luminal interfaces in cardiovascular implants.
Cooling off the heated controversy of a safer cigarette: heat-not-burn no better than traditional combustion cigarettes
Authors: Irina Petrache, Esther de Boer
Journal: Thorax (2021)

Regulatory T cells (Tregs) are critical for maintenance of peripheral tolerance in a variety of tissues. Evidence that Tregs seem to be a phenotypically diverse population that varies between individuals and tissues suggests that there may be functionally-specialized subsets of Tregs which vary depending on location and/or disease state. We developed a new mass cytometry-based method to measure FOXP3 in combination with 20 other parameters to characterize the phenotype of human Tregs in different tissues, and to enable analysis of antigen-specific cells. We first developed a protocol to detect FOXP3, the Treg lineage-defining transcription factor, via mass cytometry. We found this optimized protocol is more sensitive than commercially-available methodology to detect FOXP3 by mass cytometry and is compatible with staining of other intracellular targets such as cytokines and other transcription factors. To ask how Treg populations differ depending on location and disease state, we stained mononuclear cells from adult peripheral blood, pediatric thymus and cord blood, as well as synovial fluid from pediatric subjects with juvenile idiopathic arthritis with our Treg-specific mass cytometry panel. The resulting data were analyzed using several bioinformatics approaches including viSNE and revealed diversity in the heterogeneity and phenotype of Tregs depending on their origin. The ability to stain FOXP3 using mass cytometry will facilitate the further characterization of Tregs in health versus disease and help us understand how Tregs are functionally specialized in the context of different tissues and disease.
14q32 rearrangements deregulating <i>BCL11B </i>mark a distinct subgroup of T and myeloid immature acute leukemia
Authors: Danika Di Giacomo, Roberta La Starza, Paolo Gorello, Fabrizia Pellanera, Zeynep Kalender Atak, Kim De Keersmaecker, Valentina Pierini, Christine J Harrison, Silvia Arniani, Martina Moretti, Nicoletta Testoni, Giovanna De Santis, Giovanni Roti, Caterina Matteucci, Renato Bassan, Peter Vandenberghe, Stein Aerts, Jan Cools, Beat Bornhauser, Jean-Pierre Bourquin, Rocco Piazza, Cristina Mecucci
Journal: Blood (2021)
Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection
Authors: José Villar, Shabina Ariff, Robert B. Gunier, Ramachandran Thiruvengadam, Stephen Rauch, Alexey Kholin, Paola Roggero, Federico Prefumo, Marynéa Silva do Vale, Jorge Arturo Cardona-Perez, Nerea Maiz, Irene Cetin, Valeria Savasi, Philippe Deruelle, Sarah Rae Easter, Joanna Sichitiu, Constanza P. Soto Conti, Ernawati Ernawati, Mohak Mhatre, Jagjit Singh Teji, Becky Liu, Carola Capelli, Manuela Oberto, Laura Salazar, Michael G. Gravett, Paolo Ivo Cavoretto, Vincent Bizor Nachinab, Hadiza Galadanci, Daniel Oros, Adejumoke Idowu Ayede, Loïc Sentilhes, Babagana Bako, Mónica Savorani, Hellas Cena, Perla K. García-May, Saturday Etuk, Roberto Casale, Sherief Abd-Elsalam, Satoru Ikenoue, Muhammad Baffah Aminu, Carmen Vecciarelli, Eduardo A. Duro, Mustapha Ado Usman, Yetunde John-Akinola, Ricardo Nieto, Enrico Ferrazzi, Zulfiqar A. Bhutta, Ana Langer, Stephen H. Kennedy, Aris T. Papageorghiou
Journal: JAMA Pediatrics (2021)

Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed.
Low neutralizing antibody responses against SARS-CoV-2 in older patients with myeloma after the first BNT162b2 vaccine dose
Authors: Evangelos Terpos, Ioannis P. Trougakos, Maria Gavriatopoulou, Ioannis Papassotiriou, Aimilia D. Sklirou, Ioannis Ntanasis-Stathopoulos, Eleni-Dimitra Papanagnou, Despina Fotiou, Efstathios Kastritis, Meletios A. Dimopoulos
Journal: Blood (2021)
Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses
Authors: Carola Schäfer, Nicholas Dambrauskas, Laura M. Reynolds, Olesya Trakhimets, Andrew Raappana, Erika L. Flannery, Wanlapa Roobsoong, Jetsumon Sattabongkot, Sebastian A. Mikolajczak, Stefan H.I. Kappe, D. Noah Sather
Journal: Cell Host & Microbe (2021)

Latent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites. Although this regimen did not completely prevent primary infection, antibody-treated mice experienced 62% fewer relapses. The data constitute unprecedented direct experimental evidence that suboptimal efficacy of infection-blocking antibodies, while not completely preventing primary infection, has a pronounced benefit in reducing the number of relapses. These findings suggest that a partially efficacious pre-erythrocytic Plasmodium vivax vaccine can have a disproportionately high impact in positive public health outcomes.
The Impact of Televised Movies about Suicide
Authors: David P. Phillips, Daniel J. Paight
Journal: New England Journal of Medicine (1987)

Abstract Gould and Shaffer studied suicides by teenagers in the New York City area before and after three fictional films about suicide were televised, and presented evidence suggesting that the films were followed by a significant increase in teenage suicides. Using their methods, we studied teenage suicides in California and Pennsylvania before and after the television broadcast of the same three films. In these states, there was no evidence of an increase in teenage suicides after the films were shown. This remained true when data for New York from the study of Gould and Shaffer were combined with our data from California and Pennsylvania. We conclude that it is premature to be concerned about possibly fatal effects of fictional televised films about suicide. (N Engl J Med 1987; 317:809–11.)
Butyrate-producing human gut symbiont, <i>Clostridium butyricum</i>, and its role in health and disease
Authors: Magdalena K. Stoeva, Jeewon Garcia-So, Nicholas Justice, Julia Myers, Surabhi Tyagi, Madeleine Nemchek, Paul J. McMurdie, Orville Kolterman, John Eid
Journal: Gut Microbes (2021)

Clostridium butyricum is a butyrate-producing human gut symbiont that has been safely used as a probiotic for decades. C. butyricum strains have been investigated for potential protective or ameliorative effects in a wide range of human diseases, including gut-acquired infection, intestinal injury, irritable bowel syndrome, inflammatory bowel disease, neurodegenerative disease, metabolic disease, and colorectal cancer. In this review we summarize the studies on C. butyricum supplementation with special attention to proposed mechanisms for the associated health benefits and the supporting experimental evidence. These mechanisms center on molecular signals (especially butyrate) as well as immunological signals in the digestive system that cascade well beyond the gut to the liver, adipose tissue, brain, and more. The safety of probiotic C. butyricum strains appears well-established. We identify areas where additional human randomized controlled trials would provide valuable further data related to the strains' utility as an intervention.
Abstract 13305: Comparison of Mitral Regurgitation Severity by Echocardiography and Cardiac Magnetic Resonance Imaging Using Volumetric Quantitative Techniques and Integrative Grading
Authors: Juan C Lopez-Mattei, Kamran A Shaikh, Homam Ibrahim, Stephen H Little, Dipan J Shah, William A Zoghbi
Journal: Circulation (2012)

Background: Assessment of the severity of mitral regurgitation (MR) remains a challenge, whether quantitative techniques or an integrative approach of multiple factors are used. The degree of agree...
Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils
Authors: Camilla Margaroli, Diego Moncada-Giraldo, Dalia Arafat Gulick, Brian Dobosh, Vincent D. Giacalone, Osric A. Forrest, Fangxu Sun, Chunhui Gu, Amit Gaggar, Haydn Kissick, Ronghu Wu, Greg Gibson, Rabindra Tirouvanziam
Journal: Cell Reports Medicine (2021)

Neutrophils are often considered terminally differentiated and poised for bacterial killing. In chronic diseases such as cystic fibrosis (CF), an unexplained paradox pits massive neutrophil presence against prolonged bacterial infections. Here, we show that neutrophils recruited to CF airways in vivo and in an in vitro transmigration model display rapid and broad transcriptional firing, leading to an upregulation of anabolic genes and a downregulation of antimicrobial genes. Newly transcribed RNAs are mirrored by the appearance of corresponding proteins, confirming active translation in these cells. Treatment by the RNA polymerase II and III inhibitor α-amanitin restores the expression of key antimicrobial genes and increases the bactericidal capacity of CF airway neutrophils in vitro and in short-term sputum cultures ex vivo. Broadly, our findings show that neutrophil plasticity is regulated at the site of inflammation via RNA and protein synthesis, leading to adaptations that affect their canonical functions (i.e., bacterial clearance).