Digital Commons Network^™

Nanoscale Characterization Of Interaction Of Nucleosomes With H1 Linker Histone, Ahmed Yesvi Rafa, Shaun Filliaux, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

In eukaryotic nuclei, DNA is wrapped around an octamer of core histones to form nucleosomes. H1 binds to the linker DNA of nucleosome to form the chromatosome, the next structural unit of chromatin. Structural features on individual chromatosomes contribute to chromatin structure, but not fully characterized. In addition to canonical nucleosomes composed of two copies each of histones H2A, H2B, H3, and H4 (H3 nucleosomes), centromeres chromatin contain nucleosomes in which H3 is replaced with its analog CENP-A, changing structural properties of CENP-A nucleosomes. Nothing is known about the interaction of H1 with CENP-A nucleosomes. Here we filled this gap …

Powerless Beings: Solitary Confinement Of Humans And Nonhumans In America, Michael B. Mushlin, David N. Cassuto

Elisabeth Haub School of Law Faculty Publications

Every day, thousands of humans and millions of nonhumans endure solitary confinement. Human prisoners held this way are confined for twenty-two to twenty-four hours a day for weeks, months, or even years on end in cells the size of a parking space. For these humans, the experience is tortuous. Captive animals held in solitary confinement similarly spend much of their lives locked into tiny spaces, isolated, and deprived of the types of interactions and environment essential to their wellbeing. And, like humans, they are driven mad. In human and nonhuman settings, the agony of solitary is chillingly alike and harmful. …

Coumarin-Based Aldo-Keto Reductase Family 1c (Akr1c) 2 And 3 Inhibitors, Sravan Jonnalagadda, Ling Duan, Louise F. Dow, Geetha P. Boligala, Elizabeth A. Kosmacek, Kristyn Mccoy, Rebecca E. Oberley-Deegan, Yashpal Singh Chhonker, Darryl J. Murry, C. Patrick Reynolds, Barry J. Maurer, Trevor M. Penning, Paul C. Trippier

Journal Articles: Pharmaceutical Sciences

A series of 7-substituted coumarin derivatives have been characterized as pan-aldo-keto reductase family 1C (AKR1C) inhibitors. The AKR1C family of enzymes are overexpressed in numerous cancers where they are involved in drug resistance development. 7-hydroxy coumarin ethyl esters and their corresponding amides have high potency for AKR1C3 and AKR1C2 inhibition. Coumarin amide 3 a possessed IC50 values of 50 nM and 90 nM for AKR1C3 and AKR1C2, respectively, and exhibits 'drug-like' metabolic stability and half-life in human and mouse liver microsomes and plasma. Compound 3 a was employed as a chemical tool to determine pan-AKR1C2/3 inhibition effects both as a …

Breathe, Renee J Flores

Faculty and Staff Publications

This is a personal essay about breasts. It focuses on my experiences as a young girl, moving through adolescence to a history of breast cancer in my family, including my mother's breast cancer diagnosis. As a physician, patient, and wife, I reflect on the choices that I have to make and what this means for my identity as a woman and mother.

Control Of Hippocampal Synaptic Plasticity By Microglia-Dendrite Interactions Depends On Genetic Context In Mouse Models Of Alzheimer's Disease., Sarah E Heuer, Kelly J Keezer, Amanda A Hewes, Kristen D. Onos, Kourtney Graham, Gareth R Howell, Erik B Bloss

Faculty Research 2024

INTRODUCTION: Human data suggest susceptibility and resilience to features of Alzheimer's disease (AD) such as microglia activation and synaptic dysfunction are under genetic control. However, causal relationships between these processes, and how genomic diversity modulates them remain systemically underexplored in mouse models.

METHODS: AD-vulnerable hippocampal neurons were virally labeled in inbred (C57BL/6J) and wild-derived (PWK/PhJ) APP/PS1 and wild-type mice, and brain microglia depleted from 4 to 8 months of age. Dendrites were assessed for synapse plasticity changes by evaluating spine densities and morphologies.

RESULTS: In C57BL/6J, microglia depletion blocked amyloid-induced synaptic density and morphology changes. At a finer scale, synaptic …

Pediatric Tumors As Disorders Of Development: The Case For In Vitro Modeling Based On Human Stem Cells., Cullen D Clairmont, Joanna J Gell, Ching C Lau

Faculty Research 2024

Despite improvements in patient outcomes, pediatric cancer remains a leading cause of non-accidental death in children. Recent genetic analysis of patients with pediatric cancers indicates an important role for both germline genetic predisposition and cancer-specific somatic driver mutations. Increasingly, evidence demonstrates that the developmental timepoint at which the cancer cell-of-origin transforms is critical to tumor identity and therapeutic response. Therefore, future therapeutic development would be bolstered by the use of disease models that faithfully recapitulate the genetic context, cell-of-origin, and developmental window of vulnerability in pediatric cancers. Human stem cells have the potential to incorporate all of these characteristics into …

Spop Downregulation Promotes Bladder Cancer Progression Based On Cancer Cell-Macrophage Crosstalk Via Stat3/Ccl2/Il-6 Axis And Is Regulated By Vezf1., Meiqian Li, Yangyan Cui, Qi Qi, Jiakuan Liu, Jiaxuan Li, Guifang Huang, Jiale Yang, Jingya Sun, Zhihui Ma, Shengjie Liang, Dianzheng Zhang, Jun Jiang, Rujian Zhu, Qiuli Liu, Ruimin Huang, Jun Yan

PCOM Scholarly Works

Background: Cancer cells are intimately intertwined with tumor microenvironment (TME), fostering a symbiotic relationship propelling cancer progression. However, the interaction between cancer cells and tumor-associated macrophages (TAMs) in urothelial bladder cancer (UBC) remains poorly understood. Methods: UBC cell lines (5637, T24 and SW780), along with a monocytic cell line (U937) capable of differentiating into macrophage, were used in a co-culture system for cell proliferation and stemness by MTT, sphere formation assays. VEZF1/SPOP/STAT3/CCL2/ IL-6 axis was determined by luciferase reporter, ChIP, RNA-seq, co-IP, in vitro ubiquitination, RT-qPCR array and ELISA analyses. Results: We observed the frequent downregulation of SPOP, an E3 …

Clinical Sensitivity And Time-To-Result Of A Cascaded Pooled Testing Approach For Assessing The Prevalence And Intensity Of Schistosoma Haematobium Infection, Abraham Degarege, Bruno Levecke, Yohannes Negash, Abebe Animut, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: This study compared the clinical sensitivity and the time-to-result of an individual testing (IT) and a cascaded pooled testing approach (CPT; a positive test result in a pooled sample triggers examination of smaller-sized pools or individual samples) for assessing the prevalence and the intensity of Schistosoma haematobium infection. We also compared the sensitivity of the CPT in detecting S. haematobium infection when deploying urine filtration microscopy (UFM) vs. urine reagent strips (URS), and testing 10 mL vs. 15 mL of urine.

METHODOLOGY/PRINCIPAL FINDINGS: Between October 2021 and April 2022, S. haematobium eggs were counted in urine samples collected from …

Adgrl1 Is A Glucose Receptor Involved In Mediating Energy And Glucose Homeostasis, Kavaljit H Chhabra, Siresha Bathina, Tumininu S Faniyan, Dennis J Samuel, Muhammad Ummear Raza, Leticia Maria De Souza Cordeiro, Gonzalo Viana Di Prisco, Brady K Atwood, Jorge Robles, Lauren Bainbridge, Autumn Davis

Pharmacology and Nutritional Sciences Faculty Publications

AIMS/HYPOTHESIS: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

METHODS: Here we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to …

The Effect Of State Anxiety On Working Memory Updating, Alexandra L. Mastrangelo

PCOM Psychology Dissertations

Anxiety impairs cognition by operating to alter processing efficiency. When anxiety impairs efficiency, the capacity of working memory (WM) is confined especially for individuals who concurrently experience higher levels of anxiety (Yang et al., 2018). The updating function is a crucial process that operates within WM to replace and modify older with novel information to carry out complex cognitive tasks. However, if interference accrues from previously learned information (known as proactive interference, or PI), removing information from WM becomes more difficult. Because the relationship between state anxiety (SA) and WM is less understood compared to trait anxiety (TA), this study …

Protein-Centric Omics Analysis Reveals Circulating Complements Linked To Non-Viral Liver Diseases As Potential Therapeutic Targets, Yingzhou Shi, Hang Dong, Shiwei Sun, Xiaoqin Wu, Jiansong Fang, Jianbo Zhao, Junming Han, Zongyue Li, Huixiao Wu, Luna Liu, Wanhong Wu, Yang Tian, Guandou Yuan, Xiude Fan, Chao Xu

Faculty, Staff and Student Publications

BACKGROUND/AIMS: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.

METHODS: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.

RESULTS: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk …

Feasible Diet And Circadian Interventions Reduce In Vivo Progression Of Flt3-Itd-Positive Acute Myeloid Leukemia, Megan Rodriguez, Baharan Fekry, Brianna Murphy, Mary Figueroa, Tiewei Cheng, Margaret Raber, Lisa Wartenberg, Donna Bell, Lisa Triche, Karla Crawford, Huaxian Ma, Kendra Allton, Ruwaida Ahmed, Jaime Tran, Christine Ranieri, Marina Konopleva, Michelle Barton, Cesar Nunez, Kristin Eckel-Mahan, Joya Chandra

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia.

METHODS: The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like …

Mouse Models Of Chronic Lymphocytic Leukemia And Richter Transformation: What We Have Learnt And What We Are Missing, Maria Teresa Sabrina Bertilaccio, Shih-Shih Chen

Faculty, Staff and Student Publications

Although the chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically, unmet clinical needs are emerging, as CLL in many patients does not respond, becomes resistant to treatment, relapses during treatment, or transforms into Richter. In the majority of cases, transformation evolves the original leukemia clone into a diffuse large B-cell lymphoma (DLBCL). Richter transformation (RT) represents a dreadful clinical challenge with limited therapeutic opportunities and scarce preclinical tools. CLL cells are well known to highly depend on survival signals provided by the tumor microenvironment (TME). These signals enhance the frequency of immunosuppressive cells with protumor function, including regulatory CD4

Candidate Circulating Microrna Biomarkers In Dogs With Chronic Pancreatitis, Susan K Armstrong, Robert W Hunter, Wilna Oosthyuzen, Maciej Parys, Adam G Gow, Silke Salavati Schmitz, James W Dear, Richard J Mellanby

Faculty, Staff and Student Publications

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.

HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.

ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17).

METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, …

Phospholipid Metabolic Adaptation Promotes Survival Of Idh2 Mutant Acute Myeloid Leukemia Cells, Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa

Faculty, Staff and Student Publications

Genetic mutations in the isocitrate dehydrogenase (IDH) gene that result in a pathological enzymatic activity to produce oncometabolite have been detected in acute myeloid leukemia (AML) patients. While specific inhibitors that target mutant IDH enzymes and normalize intracellular oncometabolite level have been developed, refractoriness and resistance has been reported. Since acquisition of pathological enzymatic activity is accompanied by the abrogation of the crucial WT IDH enzymatic activity in IDH mutant cells, aberrant metabolism in IDH mutant cells can potentially persist even after the normalization of intracellular oncometabolite level. Comparisons of isogenic AML cell lines with and without IDH2 gene mutations …

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …

Clic1-Mediated Autophagy Confers Resistance To Ddp In Gastric Cancer, Zhen-Liang Nong, Kun Zhao, Ye Wang, Zhu Yu, Cong-Jun Wang, Jun-Qiang Chen

Faculty, Staff and Student Publications

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular …

A Novel Assessment Of Whole-Mount Gleason Grading In Prostate Cancer To Identify Candidates For Radical Prostatectomy: A Machine Learning-Based Multiomics Study, Jing Ning, Clemens P Spielvogel, David Haberl, Karolina Trachtova, Stefan Stoiber, Sazan Rasul, Vojtech Bystry, Gabriel Wasinger, Pascal Baltzer, Elisabeth Gurnhofer, Gerald Timelthaler, Michaela Schlederer, Laszlo Papp, Helga Schachner, Thomas Helbich, Markus Hartenbach, Bernhard Grubmüller, Shahrokh F Shariat, Marcus Hacker, Alexander Haug, Lukas Kenner

Faculty, Staff and Student Publications

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment.

Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent ⁶⁸Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics …

Toxicity In The Era Of Immune Checkpoint Inhibitor Therapy, Synat Keam, Naimah Turner, Fernanda G Kugeratski, Rene Rico, Jocelynn Colunga-Minutti, Rayansh Poojary, Sayan Alekseev, Anisha B Patel, Yuanteng Jeff Li, Ajay Sheshadri, Monica E Loghin, Karin Woodman, Ashley E Aaroe, Sarah Hamidi, Priyanka Chandrasekhar Iyer, Nicolas L Palaskas, Yinghong Wang, Roza Nurieva

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding …

Rare Genomic Copy Number Variants Implicate New Candidate Genes For Bicuspid Aortic Valve, Steven G Carlisle, Hasan Albasha, Hector I Michelena, Anna Sabate-Rotes, Lisa Bianco, Julie De Backer, Laura Muiño Mosquera, Anji T Yetman, Malenka M Bissell, Maria Grazia Andreassi, Ilenia Foffa, Dawn S Hui, Anthony Caffarelli, Yuli Y Kim, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Justin T Tretter, Kim L Mcbride, Dianna M Milewicz, Simon C Body, Siddharth K Prakash, Ebav Investigators, Bavcon Investigators

Faculty, Staff and Student Publications

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control …

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …

Novel Spirocyclic Dimer, Spid3, Targets Chronic Lymphocytic Leukemia Survival Pathways With Potent Preclinical Effects, Alexandria Eiken, Audrey L. Smith, Sydney A. Skupa, Elizabeth Schmitz, Sandeep Rana, Sarbjit Singh, Siddhartha Kumar, Jayapal Reddy Mallareddy, Aguirre A. De Cubas, Akshay Krishna, Achyuth Kalluchi, M. Jordan Rowley, Christopher R. D'Angelo, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Amarnath Natarajan, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by the induction of B-cell receptor (BCR) signaling within the tumor microenvironment (TME) driving activation of NFκB signaling and the unfolded protein response (UPR). Malignant cells have higher basal levels of UPR posing a unique therapeutic window to combat CLL cell growth using pharmacologic agents that induce accumulation of misfolded proteins. Frontline CLL therapeutics that directly target BCR signaling such as Bruton tyrosine kinase (BTK) inhibitors (e.g., ibrutinib) have enhanced patient survival. However, resistance mechanisms wherein tumor cells bypass BTK inhibition through acquired BTK mutations, and/or activation of alternative survival …

Myc Overexpression In Natural Killer Cell Lymphoma: Prognostic And Therapeutic Implications, Chengfeng Bi, Yuhua Huang, Roshia Ali, Fang Wang, Xia Yang, Alyssa Bouska, Lu Xu, Xinbao Hao, Matthew A. Lunning, Wing C. Chan, Javeed Iqbal, Dennis D. Weisenburger, Julie M. Vose, Kai Fu

Journal Articles: Oncology and Hematology

The current clinical management of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the prognostic index of NK cells lymphoma with Epstein-Barr virus (PINK-E) prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown in NK …

A Modified Nucleoside O6-Methyl-2'-Deoxyguanosine-5'-Triphosphate Exhibits Anti-Glioblastoma Activity In A Caspase-Independent Manner., Zi-Hui Wang, Jin Li, Qian Liu, Jian-Chang Qian, Qing-Qing Li, Qing-Yu Wang, Lv-Tao Zeng, Si-Jia Li, Xin Gao, Jia-Xin Pan, Xu-Fan Gao, Kun Wu, Guo-Xin Hu, Tomoo Iwakuma, Jian-Ping Cai

Manuscripts, Articles, Book Chapters and Other Papers

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Prediction Of Recurrent Lateral Ankle Sprain And Ankle Pain Using Applied Care Strategies And Patient-Reported Outcomes, Ryan S. Mccann, Elisabeth Ohrnberger, Kyle B. Kosik, Phillip A. Gribble

Rehabilitation Sciences Faculty Publications

Context

Patients with lateral ankle sprains (LASs) often have deficient patient-reported outcomes (PROs) at return to activity (RTA), potentially increasing risk for recurrent LAS and ankle pain. Additionally, applied care strategies are known to correct impairments, but their ability to mitigate risk for long-term consequences remains unknown.

Objective

To determine if applied care strategies and PRO scores at RTA and 6 months after RTA predict recurrent LAS and ankle pain 12 months after an acute LAS. DESIGN: Prospective cohort study.

Setting

Online survey.

Patients or Other Participants

We enrolled 63 individuals within 1 week of sustaining an acute LAS.

Main …

Radiation Induced Skin Fibrosis (Risf): Opportunity For Angiotensin Ii-Dependent Intervention, Patricia F. Boothe, Vidya P. Kumar, Yali Kong, Kan Wang, Howard Levinson, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. …

Bet Inhibition Reforms The Immune Microenvironment And Alleviates T Cell Dysfunction In Chronic Lymphocytic Leukemia, Audrey L. Smith, Sydney A. Skupa, Alexandria P. Eiken, Timothy E. Reznicek, Elizabeth Schmitz, Nolan Williams, Dalia Y. Moore, Christopher R. D'Angelo, Avyakta Kallam, Matthew A. Lunning, Gregory Bociek, Julie M. Vose, Eslam Mohamed, Anna R. Mahr, Paul W. Denton, Ben Powell, Gideon Bollag, M. Jordan Rowley, Dalia El-Gamal

Journal Articles: Oncology and Hematology

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eμ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer …

Statins And The Risk Of Pancreatic Cancer: A Systematic Review And Meta-Analysis Of 2,797,186 Patients, Eryka Karbowska, Damian Swieczkowski, Aleksandra Gasecka, Michal Pruc, Kamil Safiejko, Jerzy R Ladny, Tomasz Kopiec, Milosz J Jaguszewski, Krzysztof J Filipiak, Zubaid Rafique, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: Statin use in many studies is related to the improvement of a patients' condition including reducing the risk of various malignancies. Herein, is a systematic review and meta-analysis to examine the evidence on the association between statin therapy and the risk of the occurrence of pancreatic cancer, mainly in terms of decreased risk of developing pancreatic cancer among patients using statin therapy in the long-term perspective.

METHODS: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to December 1st, 2021. Random effect models were used to estimate summary odds ratios …

Generation And Characterization Of In Vitro Transcribed Mrna, Cristina Poveda, Yi-Lin Chen, Ulrich Strych

Faculty, Staff and Students Publications

Here we describe the in vitro preparation of mRNA from DNA templates, including setting up the transcription reaction, mRNA capping, and mRNA labeling. We then describe methods used for mRNA characterization, including UV and fluorescence spectrophotometry, as well as gel electrophoresis. Moreover, characterization of the in vitro transcribed RNA using the Bioanalyzer instrument is described, allowing a higher resolution analysis of the target molecules. For the in vitro testing of the mRNA molecules, we include protocols for the transfection of various primary cell cultures and the confirmation of translation by intracellular staining and western blotting.