Medical Specialties Commons^™

Fifteen Years Of Irinotecan Therapy For Pediatric Sarcoma: Where To Next?, Lars M. Wagner

Pediatrics Faculty Publications

Over the past 15 years, irinotecan has emerged as an important agent for treating pediatric sarcoma patients. This review summarizes the activity noted in previous studies, and outlines current issues regarding scheduling, route of administration, and amelioration of side effects. Also discussed are new pegylated and nanoliposomal formulations of irinotecan and its active metabolite, SN-38, as well as future plans for how irinotecan may be used in combination with other conventional cytotoxic as well as targeted agents.

Insights Into Alzheimer’S Disease: The Levels Of Signaling Proteins In Brain Of Control Subjects Versus Brain From Subjects With Mild Cognitive Impairment, Georgianne F. Tiu

Kaleidoscope

The purpose of this study was to measure the expression levels of key signaling proteins in brain tissue from subjects with mild cognitive impairment (MCI) compared to control subjects. MCI is considered to be the beginning phase of Alzheimer’s disease (AD). Tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κβ), phospho Bad (pBad), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) are four of the proteins that were investigated. Trends of either decreases or increases in protein expression levels in MCI vs. control brain were investigated. Western blot analysis was used in order to identify these trends. These signaling protein levels are …

Left Ventricular Mechanical Dysfunction In Diet-Induced Obese Mice Is Exacerbated During Inotropic Stress: A Cine Dense Cardiovascular Magnetic Resonance Study, Christopher M. Haggerty, Andrea C. Mattingly, Sage P. Kramer, Cassi M. Binkley, Linyuan Jing, Jonathan D. Suever, David K. Powell, Richard J. Charnigo, Frederick H. Epstein, Brandon K. Fornwalt

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Obesity is a risk factor for cardiovascular disease. There is evidence of impaired left ventricular (LV) function associated with obesity, which may relate to cardiovascular mortality, but some studies have reported no dysfunction. Ventricular function data are generally acquired under resting conditions, which could mask subtle differences and potentially contribute to these contradictory findings. Furthermore, abnormal ventricular mechanics (strains, strain rates, and torsion) may manifest prior to global changes in cardiac function (i.e., ejection fraction) and may therefore represent more sensitive markers of cardiovascular disease. This study evaluated LV mechanics under both resting and stress conditions with the hypothesis …

Chronic Ldh Elevation After Left Ventricular Assist Device Implantation, Hesham R. Omar, Navin Rajagopalan, Maya Guglin

The VAD Journal

A 61-year-old woman who underwent HeartMate II left ventricular assist device placement for non-ischemic cardiomyopathy developed elevated lactate dehydrogenase within two weeks after implantation. After eight months of observation and several hospital admissions during which there was no evidence of pump thrombosis, she presented with clinically manifest hemolysis. During pump exchange there was notable pannus formation on the inflow cannula of the left ventricular assist device. The pannus around the inflow likely existed for several months, limiting the flow and creating a low-grade hemolysis and this low flow state stimulated thrombus formation triggering gross hemolysis. Thoratec analysis of the pump …

Chronic Hemodialysis In A Patient With Left Ventricular Assist Device., Amr Idris, Georges Lolay, Ana L. Castellanos, Navin Rajagopalan, Maya Guglin

The VAD Journal

Renal dysfunction in the setting of heart failure is a common medical problem. This dysfunction can range from reversible ischemic changes to renal failure requiring renal replacement therapy. Patients who are candidates for mechanical circulatory support with left ventricular assistant device (LVAD) pose unique challenge with respect to receiving dialysis. We present a 47 year old patient who required renal replacement therapy peri-implantation of LVAD for management of acute on chronic kidney disease, and was discharged for chronic hemodialysis in an outpatient setting. In this report we highlight the challenges of managing volume overload in patients with impaired renal function …

Phases Of Su(3) Gauge Theories With Fundamental Quarks Via Dirac Spectral Density, Andrei Alexandru, Ivan Horváth

Anesthesiology Faculty Publications

We propose that, in SU(3) gauge theories with fundamental quarks, confinement can be inferred from spectral density of the Dirac operator. This stems from the proposition that its possible behaviors are exhausted by three distinct types (Fig. 1). The monotonic cases are standard and entail confinement with valence chiral symmetry breaking (A) or the lack of both (C,C’). The bimodal (anomalous) option (B) was frequently regarded as an artifact (lattice or other) in previous studies, but we show for the first time that it persists in the continuum limit, and conclude that it informs of a nonconfining …

Increased Expression Of Fatty Acid Synthase Provides A Survival Advantage To Colorectal Cancer Cells Via Upregulation Of Cellular Respiration, Yekaterina Y. Zaytseva, Jennifer W. Harris, Mihail I. Mitov, Ji Tae Kim, D. Allan Butterfield, Eun Young Lee, Heidi L. Weiss, Tianyan Gao, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN), a lipogenic enzyme, is upregulated in colorectal cancer (CRC). Increased de novo lipid synthesis is thought to be a metabolic adaptation of cancer cells that promotes survival and metastasis; however, the mechanisms for this phenomenon are not fully understood. We show that FASN plays a role in regulation of energy homeostasis by enhancing cellular respiration in CRC. We demonstrate that endogenously synthesized lipids fuel fatty acid oxidation, particularly during metabolic stress, and maintain energy homeostasis. Increased FASN expression is associated with a decrease in activation of energy-sensing pathways and accumulation of lipid droplets in CRC cells …

Inner Synovial Membrane Footprint Of The Anterior Elbow Capsule: An Arthroscopic Boundary, Srinath Kamineni, Abdo Bachoura, Koichi Sasaki, Danielle Reilly, Kate N. Harris, Anthony Sinai, Andrew Deane

Orthopaedic Surgery and Sports Medicine Faculty Publications

Introduction. The purpose of this study is to describe the inner synovial membrane (SM) of the anterior elbow capsule, both qualitatively and quantitatively. Materials and Methods. Twenty-two cadaveric human elbows were dissected and the distal humerus and SM attachments were digitized using a digitizer. The transepicondylar line (TEL) was used as the primary descriptor of various landmarks. The distance between the medial epicondyle and medial SM edge, SM apex overlying the coronoid fossa, the central SM nadir, and the apex of the SM insertion overlying the radial fossa and distance from the lateral epicondyle to lateral SM edge along the …

A Case Study Of The Impediments To The Commercialization Of Research At The University Of Kentucky, Nathan L. Vanderford, Elizabeth Marcinkowski

Markey Cancer Center Faculty Publications

The commercialization of university-based research occurs to varying degrees between academic institutions. Previous studies have found that multiple barriers can impede the effectiveness and efficiency by which academic research is commercialized. This case study was designed to better understand the impediments to research commercialization at the University of Kentucky via a survey and interview with three successful academic entrepreneurs. The study also garnered insight from the individuals as to how the commercialization process could be improved. Issues with commercialization infrastructure; a lack of emphasis, at the university level, on the importance of research commercialization; a void in an entrepreneurial culture …

Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander

Gill Heart & Vascular Institute Faculty Publications

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.

Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …

Sleeping While Driving, Joav Merrick, Stephanie Stockburger, Hatim A. Omar

Pediatrics Faculty Publications

No abstract provided.

4e-Bp1 As An Oncotarget, Qing-Bai She

Markey Cancer Center Faculty Publications

No abstract provided.

Pp2a Inhibitors Arrest G2/M Transition Through Jnk/Sp1-Dependent Down-Regulation Of Cdk1 And Autophagy-Dependent Up-Regulation Of P21, Fei-Ran Gong, Meng-Yao Wu, Meng Shen, Qiaoming Zhi, Ze-Kuan Xu, Rong Wang, Wen-Jie Wang, Yang Zong, Zeng-Liang Li, Yadi Wu, Binhua P. Zhou, Kai Chen, Min Tao, Wei Li

Markey Cancer Center Faculty Publications

Protein phosphatase 2A (PP2A) plays an important role in the control of the cell cycle. We previously reported that the PP2A inhibitors, cantharidin and okadaic acid (OA), efficiently repressed the growth of cancer cells. In the present study, we found that PP2A inhibitors arrested the cell cycle at the G2 phase through a mechanism that was dependent on the JNK pathway. Microarrays further showed that PP2A inhibitors induced expression changes in multiple genes that participate in cell cycle transition. To verify whether these expression changes were executed in a PP2A-dependent manner, we targeted the PP2A catalytic subunit (PP2Ac) using siRNA …

Reversal Of Aging-Related Neuronal Ca2+ Dysregulation And Cognitive Impairment By Delivery Of A Transgene Encoding Fk506-Binding Protein 12.6/1b To The Hippocampus, John C. Gant, Kuey-Chu Chen, Inga Kadish, Eric M. Blalock, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer's disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. …

Profile Of Veliparib And Its Potential In The Treatment Of Solid Tumors, Lars M. Wagner

Pediatrics Faculty Publications

Inhibition of poly(ADP-ribose) polymerase (PARP) is an attractive therapeutic strategy because of the importance of this pathway in restoring DNA damage. Small-molecule inhibitors of PARP appear most effective when used to treat tumors with underlying defects in DNA repair, or when combined with DNA-damaging agents. Veliparib is one of several recently developed oral inhibitors of PARP currently in clinical trials. This review summarizes the pharmacology, mechanisms of action, toxicity, and activity of veliparib seen in clinical trials to date. Also discussed are proposed mechanisms of resistance, potential biomarkers of activity, and issues regarding patient selection and combination therapies that may …

Veraflo Negative Pressure Wound Therapy With Household Bleach For Refractory Driveline Infection In A Patient With Left Ventricular Assist Device., Amr Idris, Amanda Hart, Sarah Branam, Maya Guglin

The VAD Journal

Driveline infections and sepsis are amongst the most common causes of morbidity and mortality in a patient with a left ventricular assist device. In this case, we present a patient with a multi drug resistant pseudomonas aeruginosa driveline exit site infection. Initially, it was treated with dual antibiotics, followed by surgical debridement utilizing Dakin’s solution irrigation and standard negative pressure wound therapy. Wound healing was minimal determined by poor granulation appearance, unchanged size from surgical debridement, purulent drainage, and the wound base remained colonized with multi drug resistant pseudomonas aeruginosa. A novel treatment of VeraFlo negative pressure wound therapy in …

Targeted Dna Damage At Individual Telomeres Disrupts Their Integrity And Triggers Cell Death, Luxi Sun, Rong Tan, Jianquan Xu, Justin Laface, Ying Gao, Yanchun Xiao, Myriam Attar, Carola Neumann, Guo-Min Li, Bing Su, Yang Liu, Satoshi Nakajima, Arthur S. Levine, Li Lan

Markey Cancer Center Faculty Publications

Cellular DNA is organized into chromosomes and capped by a unique nucleoprotein structure, the telomere. Both oxidative stress and telomere shortening/dysfunction cause aging-related degenerative pathologies and increase cancer risk. However, a direct connection between oxidative damage to telomeric DNA, comprising <1% of the genome, and telomere dysfunction has not been established. By fusing the KillerRed chromophore with the telomere repeat binding factor 1, TRF1, we developed a novel approach to generate localized damage to telomere DNA and to monitor the real time damage response at the single telomere level. We found that DNA damage at long telomeres in U2OS cells is not repaired efficiently compared to DNA damage in non-telomeric regions of the same length in heterochromatin. Telomeric DNA damage shortens the average length of telomeres and leads to cell senescence in HeLa cells and cell death in HeLa, U2OS and IMR90 cells, when DNA damage at non-telomeric regions is undetectable. Telomere-specific damage induces chromosomal aberrations, including chromatid telomere loss and telomere associations, distinct from the damage induced by ionizing irradiation. Taken together, our results demonstrate that oxidative damage induces telomere dysfunction and underline the importance of maintaining telomere integrity upon oxidative damage.

Sex Differences In Clinical Features Of Early, Treated Parkinson's Disease, Erika F. Augustine, Adriana Pérez, Rohit Dhall, Chizoba C. Umeh, Aleksandar Videnovic, Franca Cambi, Anne-Marie A. Wills, Jordan J. Elm, Richard M. Zweig, Lisa M. Shulman, Martha A. Nance, Jacquelyn Bainbridge, Oksana Suchowersky

Neurology Faculty Publications

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.

METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

Altered Lysosomal Proteins In Neural-Derived Plasma Exosomes In Preclinical Alzheimer Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy.

METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker.

RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane …

Regression Of Gastric Cancer By Systemic Injection Of Rna Nanoparticles Carrying Both Ligand And Sirna, Daxiang Cui, Chunlei Zhang, Bing Liu, Yi Shu, Tong Du, Dan Shu, Kan Wang, Fangping Dai, Yanlei Liu, Chao Li, Fei Pan, Yuming Yang, Jian Ni, Hui Li, Beate Brand-Saberi, Peixuan Guo

Markey Cancer Center Faculty Publications

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells …

Radiobiological Evaluation Of Intensity Modulated Radiation Therapy Treatments Of Patients With Head And Neck Cancer: A Dual-Institutional Study, G. Narayanasamy, A. P. Pyakuryal, S. Pandit, J. Vincent, C. Lee, P. Mavroidis, N. Papanikolaou, Mahesh Kudrimoti, T. T. Sio

Radiation Medicine Faculty Publications

In clinical practice, evaluation of clinical efficacy of treatment planning stems from the radiation oncologist's experience in accurately targeting tumors, while keeping minimal toxicity to various organs at risk (OAR) involved. A more objective, quantitative method may be raised by using radiobiological models. The purpose of this work is to evaluate the potential correlation of OAR-related toxicities to its radiobiologically estimated parameters in simultaneously integrated boost (SIB) intensity modulated radiation therapy (IMRT) plans of patients with head and neck tumors at two institutions. Lyman model for normal tissue complication probability (NTCP) and the Poisson model for tumor control probability (TCP) …

Role Of Mitochondria In Regulating Microrna Activity And Its Relevance To The Central Nervous System, Wang-Xia Wang, Joe E. Springer

Physical Medicine and Rehabilitation Faculty Publications

No abstract provided.

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …

Low Neural Exosomal Levels Of Cellular Survival Factors In Alzheimer's Disease, Edward J. Goetzl, Adam Boxer, Janice B. Schwartz, Erin Abner, Ronald C. Petersen, Bruce L. Miller, Olga D. Carlson, Maja Mustapic, Dimitrios Kapogiannis

Sanders-Brown Center on Aging Faculty Publications

Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock factor-1, and repressor element 1-silencing transcription factor all were significantly lower in Alzheimer's disease patients than controls (P < 0.0001). In frontotemporal dementia, the only significant difference was higher levels of repressor element 1-silencing transcription factor than in controls. Exosomal transcription factors were diminished 2-10 years before clinical diagnosis of Alzheimer's disease. Low exosomal levels of survival proteins may explain decreased neuronal resistance to Alzheimer's disease neurotoxic proteins.

Quality Of Life Of Parents Of Children With Asthma, Anna Trzcieniecka-Green, Kamilla Bargiel-Matusiewicz, Agnieszka Wilczyńska, Hatim A. Omar

Pediatrics Faculty Publications

An increased frequency of asthma in children has been lately observed. The course of asthma depends not only on treatment, but also on the actions taken by the parents of a sick child. Design: A non-experimental cross-sectional design. Methods: In this study the Pediatric Asthma Quality of Life Questionnaire (PACQLQ) and Satisfaction with Life Scale (SWLS) were administered to 60 parents of children with asthma. Two groups of parents were compared. The first group consisted of parents of children who had been diagnosed with asthma less than three months before the beginning of the study. The second group consisted of …

Inotropes Are Linked To Increased Mortality In Heart Failure, M. Chadi Alraies, Bill Tran, Sirtaz Adatya

The VAD Journal

No abstract provided.

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Inotropes Are Not Linked To Increased Mortality In Heart Failure, Maya Guglin

The VAD Journal

How to use inotropes is one of the most controversial topics in the management of heart failure. While most clinicians use these drugs, and recognize the state of inotrope dependency, current guidelines recommend them onlu as a bridge or palliation. Thus, inotropes are considered either neutral or detrimental in terms of outcomes. Meanwhile, properly designed randomized clinical trials testing the outcomes on inotropes, have never been performed and it is unlikely that they will ever be attempted. These trials would require randomizing patients with advanced heart failure, low output syndrome, and impaired end-organ perfusion into groups that received or not …

Iron Toxicity In The Retina Requires Alu Rna And The Nlrp3 Inflammasome, Bradley D. Gelfand, Charles B. Wright, Younghee Kim, Tetsuhiro Yasuma, Reo Yasuma, Shengjian Li, Benjamin J. Fowler, Ana Bastos-Carvalho, Nagaraj Kerur, Annette Uittenbogaard, Youn Seon Han, Dingyuan Lou, Mark E. Kleinman, W. Hayes Mcdonald, Gabriel Núñez, Philippe Georgel, Joshua L. Dunaief, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Excess iron induces tissue damage and is implicated in age-related macular degeneration (AMD). Iron toxicity is widely attributed to hydroxyl radical formation through Fenton's reaction. We report that excess iron, but not other Fenton catalytic metals, induces activation of the NLRP3 inflammasome, a pathway also implicated in AMD. Additionally, iron-induced degeneration of the retinal pigmented epithelium (RPE) is suppressed in mice lacking inflammasome components caspase-1/11 or Nlrp3 or by inhibition of caspase-1. Iron overload increases abundance of RNAs transcribed from short interspersed nuclear elements (SINEs): Alu RNAs and the rodent equivalent B1 and B2 RNAs, which are inflammasome agonists. Targeting …