Digital Commons Network^™

Why Does The X Chromosome Lag Behind Autosomes In Gwas Findings?, Ivan P Gorlov, Christopher I Amos

Faculty, Staff and Students Publications

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage …

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Synthetic Assembly Dna Cloning To Build Plasmids For Multiplexed Transgenic Selection, Counterselection Or Any Other Genetic Strategies Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Alejandro Sarrion-Perdigones, Herman A Dierick

Faculty, Staff and Students Publications

We recently described a drug-based selectable and counterselectable genetic platform for the animal model system Drosophila melanogaster, consisting of four resistance and two sensitivity markers that allow direct selection for, or counterselection against, a desired genotype. This platform eliminates the need to identify modified progeny by traditional laborious screening using dominant eye and body color markers, white⁺ and yellow⁺, respectively. The four resistance markers permit selection of animals using G418 sulfate, Puromycin HCl, Blasticidin S, or Hygromycin B, while the two sensitivity markers allow counterselection of animals against Ganciclovir or Acyclovir, and 5-Fluorocytosine. The six markers …

Characterizing Mechanism-Based Pain Phenotypes In Patients With Chronic Pancreatitis: A Cross-Sectional Analysis Of The Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies, Jami L Saloman, Darwin L Conwell, Evan Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Anna Evans Phillips, Mark Topazian, Stephen K Van Den Eeden, Jose Serrano, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N …

Modeling Ewing Sarcoma Lung Metastasis, Atreyi Dasgupta, Lyazat Kurenbekova, Tajhal D Patel, Kimal Rajapakshe, Gargi Ghosal, Bikesh Nirala, Cristian Coarfa, Jason Yustein

Faculty, Staff and Students Publications

Ewing Sarcoma (EwS) is the second most common malignant bone tumor in adolescents and young adults. The single-most powerful predictor of outcome in EwS is presence of metastatic burden at the time of diagnosis. Patients with metastatic Ewing Sarcoma have an abysmal 5-year survival rate of 10–25%, which has not changed over the past 30–40 years. Thus, unraveling underlying mechanisms of EwS metastasis are imperative for developing effective therapeutic measures. Investigations towards this goal are limited by the lack of reliable genetically engineered mouse models and specialized metastatic models. Using two established cell lines, A673 and TC71, we generated lung …

Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun

Faculty, Staff and Students Publications

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic …

Fibrinogen-Like Protein 2: Its Biological Function Across Cell Types And The Potential To Serve As An Immunotherapy Target For Brain Tumors, Sheng Zhang, Ganesh Rao, Amy Heimberger, Shulin Li

Faculty, Staff and Student Publications

Brain tumors are among the 10 leading causes of cancer-related death and present unique treatment challenges due to their critical location, genetic heterogeneity, and the blood-brain barrier. Recent advances in targeted immunotherapy and immune checkpoint blocking therapy provide alternative therapeutic strategies for brain tumors. Fibrinogen-like protein 2 (FGL2), which induces transformation from low-grade glioma to high-grade glioblastoma, is a type II membrane protein that is highly expressed in both host immune cells and tumor cells. Studies have uncovered multiple forms of FGL2 proteins with a broad range of roles in inducing immune tolerance and avoiding immune surveillance in tumor cells. …

Serial Recombineering Cloning To Build Selectable And Tagged Genomic P[Acman] Bac Clones For Selection Transgenesis And Functional Gene Analysis Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick

Faculty, Staff and Students Publications

Transgenes with genomic DNA fragments that encompass genes of interest are the gold standard for complementing null alleles in rescue experiments in the fruit fly Drosophila melanogaster. Of particular interest are genomic DNA clones available as bacterial artificial chromosomes (BACs) or fosmids from publicly available genomic DNA libraries. Genes contained within BAC and fosmid clones can be easily modified by recombineering cloning to insert peptide or protein tags to localize, visualize, or manipulate gene products, and to create point mutations or deletions for structure-function analysis of the inserted genes. However, since transgenesis efficiency is inversely correlated with transgene size, obtaining …

Multiplexed Transgenic Selection And Counterselection Strategies To Expedite Genetic Manipulation Workflows Using Drosophila Melanogaster, Koen J T Venken, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick

Faculty, Staff and Students Publications

We recently described a set of four selectable and two counterselectable markers that provide resistance and sensitivity, respectively, against their corresponding drugs using the model organism Drosophila melanogaster. The four selectable markers provide animal resistance against G418 sulfate, Puromycin HCl, Blasticidin S, or Hygromycin B, while the two counterselection markers make animals sensitive to Ganciclovir/Acyclovir, or 5-Fluorocytosine. Unlike classical phenotypic markers, visual or fluorescent, which require extensive screening progeny of a genetic cross for desired genotypes, resistance and sensitivity markers eliminate this laborious procedure by directly selecting for, or counterselecting against, the desired genotypes. We demonstrated the usefulness of …

Pediatric Rhabdomyosarcoma Incidence And Survival In The United States: An Assessment Of 5656 Cases, 2001–2017, Matthew T Mcevoy, David A Siegel, Shifan Dai, Mehmet Fatih Okcu, Mark Zobeck, Rajkumar Venkatramani, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: While rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, past epidemiology studies of this malignancy used data that covered

METHODS: Incidence and survival were assessed for pediatric patients diagnosed with RMS during 2003-2017 and 2001-2016, respectively. Both demographic and clinical variables were evaluated. Age-adjusted incidence rates, average annual percent change (AAPC), and 5-year relative survival (RS) were calculated, all with corresponding 95% confidence intervals (CIs). Cox regression models were used to evaluate the impact of demographic and clinical variables on survival.

RESULTS: We identified 5656 primary RMS cases in USCS during 2003-2017. The age-adjusted …

Molecular Mechanisms Regulating Wound Repair: Evidence For Paracrine Signaling From Corneal Epithelial Cells To Fibroblasts And Immune Cells Following Transient Epithelial Cell Treatment With Mitomycin C, Sonali Pal-Ghosh, Beverly A Karpinski, Himani Datta Majumdar, Trisha Ghosh, Julie Thomasian, Stephen R Brooks, Andrew P Sawaya, Maria I Morasso, Kaitlin K Scholand, Cintia S De Paiva, Jeremias G Galletti, Mary Ann Stepp

Faculty, Staff and Students Publications

In this paper, we use RNAseq to identify senescence and phagocytosis as key factors to understanding how mitomyin C (MMC) stimulates regenerative wound repair. We use conditioned media (CM) from untreated (CMC) and MMC treated (CMM) human and mouse corneal epithelial cells to show that corneal epithelial cells indirectly exposed to MMC secrete elevated levels of immunomodulatory proteins including IL-1α and TGFβ1 compared to cells exposed to CMC. These factors increase epithelial and macrophage phagocytosis and promote ECM turnover. IL-1α supplementation can increase phagocytosis in control epithelial cells and attenuate TGFβ1 induced αSMA expression by corneal fibroblasts. Yet, we show …

An Integrated Multi-Omics Analysis Of Sleep-Disordered Breathing Traits Implicates P2xr4 Purinergic Signaling, Nuzulul Kurniansyah, Danielle A Wallace, Ying Zhang, Bing Yu, Brian Cade, Heming Wang, Heather M Ochs-Balcom, Alexander P Reiner, Alberto R Ramos, Joshua D Smith, Jianwen Cai, Martha Daviglus, Phyllis C Zee, Robert Kaplan, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Sina A Gharib, Susan Redline, Tamar Sofer

Faculty, Staff and Student Publications

Sleep Disordered Breathing (SDB) is a common disease associated with increased risk for cardiometabolic, cardiovascular, and cognitive diseases. How SDB affects the molecular environment is still poorly understood. We study the association of three SDB measures with gene expression measured using RNA-seq in multiple blood tissues from the Multi-Ethnic Study of Atherosclerosis. We develop genetic instrumental variables for the associated transcripts as polygenic risk scores (tPRS), then generalize and validate the tPRS in the Women's Health Initiative. We measure the associations of the validated tPRS with SDB and serum metabolites in Hispanic Community Health Study/Study of Latinos. Here we find …

Gene Expression Profiling Of Circulating Tumor Cells Captured By Microcavity Array Is Superior To Enumeration In Demonstrating Therapy Response In Patients With Newly Diagnosed Advanced And Locally Advanced Non-Small Cell Lung Cancer, Evan N Cohen, Gitanjali Jayachandran, Hui Gao, Phillip Peabody, Heather B Mcbride, Franklin D Alvarez, Pablo Lopez Bravo, Wei Qiao, Suyu Liu, Luyang Yao, Steven H Lin, James M Reuben

Faculty, Staff and Student Publications

Background: Circulating tumor cells (CTCs) are a promising non-invasive tool for monitoring therapy response. The only Food and Drug Administration (FDA)-approved test is limited to enumeration of epithelial CTC without further characterization and is not approved for the management of non-small cell lung cancer (NSCLC). Here we use a MicroCavity Array (MCA) system to capture CTC agnostic of epithelial markers for further molecular testing in NSCLC.

Methods: CTCs were enumerated by fluorescent microscopy as longitudinal sampling throughout disease management from 213 NSCLC patients. CTC-enriched samples from a subset of 127 patients were interrogated for gene expression by reverse transcription polymerase …

A Delicate Balance Between Antibody Evasion And Ace2 Affinity For Omicron Ba275, Jiandong Huo, Aiste Dijokaite-Guraliuc, Chang Liu, Daming Zhou, Helen M Ginn, Raksha Das, Piyada Supasa, Muneeswaran Selvaraj, Rungtiwa Nutalai, Aekkachai Tuekprakhon, Helen M E Duyvesteyn, Alexander J Mentzer, Donal Skelly, Thomas G Ritter, Ali Amini, Sagida Bibi, Sandra Adele, Sile Ann Johnson, Neil G Paterson, Mark A Williams, David R Hall, Megan Plowright, Thomas A H Newman, Hailey Hornsby, Thushan I De Silva, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J Dunachie, Andrew J Pollard, Teresa Lambe, Philip Goulder, Optic Consortium, Isaric4c Consortium, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused successive global waves of infection. These variants, with multiple mutations in the spike protein, are thought to facilitate escape from natural and vaccine-induced immunity and often increase in affinity for ACE2. The latest variant to cause concern is BA.2.75, identified in India where it is now the dominant strain, with evidence of wider dissemination. BA.2.75 is derived from BA.2 and contains four additional mutations in the receptor-binding domain (RBD). Here, we perform an antigenic and biophysical characterization of BA.2.75, revealing an interesting balance between humoral evasion and ACE2 receptor …

Association Between Covid-19 And Postoperative Neurological Complications And Antipsychotic Medication Use After Cancer Surgery: A Retrospective Study, Juan P Cata, Jian Hu, Lei Feng, Caroline Chung, Scott E Woodman, Larissa A Meyer

Faculty, Staff and Student Publications

Introduction: Millions of Americans infected with the severe acute respiratory syndrome-associated coronavirus-19 (COVID-19) need oncologic surgery. Patients with acute or resolved COVID-19 illness complain of neuropsychiatric symptoms. How surgery affects postoperative neuropsychiatric outcomes such as delirium is unknown. We hypothesize that patients with a history of COVID-19 could have an exaggerated risk of developing postoperative delirium after undergoing major elective oncologic surgery.

Methods: We conducted a retrospective study to determine the association between COVID-19 status and antipsychotic drugs during postsurgical hospitalization as a surrogate of delirium. Secondary outcomes included 30 days of postoperative complications, length of stay, and mortality. Patients …

Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the …

Nonhuman Primate Genetic Models For The Study Of Rare Diseases, Eric J Vallender, Charlotte E Hotchkiss, Anne D Lewis, Jeffrey Rogers, Joshua A Stern, Samuel M Peterson, Betsy Ferguson, Ken Sayers

Faculty, Staff and Students Publications

Pre-clinical research and development relies heavily upon translationally valid models of disease. A major difficulty in understanding the biology of, and developing treatments for, rare disease is the lack of animal models. It is important that these models not only recapitulate the presentation of the disease in humans, but also that they share functionally equivalent underlying genetic causes. Nonhuman primates share physiological, anatomical, and behavioral similarities with humans resulting from close evolutionary relationships and high genetic homology. As the post-genomic era develops and next generation sequencing allows for the resequencing and screening of large populations of research animals, naturally occurring …

Mutations In The Transcriptional Regulator Mecp2 Severely Impact Key Cellular And Molecular Signatures Of Human Astrocytes During Maturation, Jialin Sun, Sivan Osenberg, Austin Irwin, Li-Hua Ma, Nigel Lee, Yangfei Xiang, Feng Li, Ying-Wooi Wan, In-Hyun Park, Mirjana Maletic-Savatic, Nurit Ballas

Faculty, Staff and Students Publications

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether MECP2 mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing MECP2 mutations greatly impact the key role of astrocytes in regulating overall brain bioenergetics and that these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal maturation, astrocytes rely on neurons to induce their complex stellate morphology and transcriptional changes. While MECP2 mutations cause cell-intrinsic aberrations in the astrocyte transcriptional landscape, surprisingly, they do not affect the neuron-induced …

What Did We Learn About Vads In 2022?, Maya Guglin

The VAD Journal

This is our 9^th annual literature review on mechanical circulatory support devices. Our previous reports were well received by the readers.

In this paper, we summarized the most interesting and important, from our standpoint, publications from 2022. There may be some slight overlap with the end of 2021 because some papers were published online first, and the year of the publication changed when they became available in print.

For the sixth time, we wrote a section on extracorporeal membrane oxygenation (ECMO) which primarily addresses new developments in veno-arterial ECMO.

Readers who wish to supplement this review, argue with the …

Extracellular Matrix (Ecm) And Fibrosis In Adipose Tissue: Overview And Perspectives, Kai Sun, Xin Li, Philipp E Scherer

Faculty, Staff and Student Publications

Fibrosis in adipose tissue is a major driver of obesity-related metabolic dysregulation. It is characterized by an overaccumulation of extracellular matrix (ECM) during unhealthy expansion of adipose tissue in response to over nutrition. In obese adipose-depots, hypoxia stimulates multiple pro-fibrotic signaling pathways in different cell populations, thereby inducing the overproduction of the ECM components, including collagens, noncollagenous proteins, and additional enzymatic components of ECM synthesis. As a consequence, local fibrosis develops. The result of fibrosis-induced mechanical stress not only triggers cell necrosis and inflammation locally in adipose tissue but also leads to system-wide lipotoxicity and insulin resistance. A better understanding …

Extradural Primary Malignant Spinal Tumors In A Population Younger Than 25 Years: An Ambispective International Multicenter Study On Onco-Surgical Outcomes, Alexander C Disch, Stefano Boriani, Alessandro Luzzati, Laurence D Rhines, Charles G Fisher, Aron Lazary, Ziya L Gokaslan, Dean Chou, Michelle J Clarke, Michael G Fehlings, Klaus-Dieter Schaser, Nicole M Germscheid, Jeremy J Reynolds, The Ao Spine Knowledge Forum Tumor

Faculty, Staff and Student Publications

Extradural malignant primary spinal tumors are rare and outcome data, especially for younger patients, is limited. In a worldwide (11 centers) study (Predictors of Mortality and Morbidity in the Surgical Management of Primary Tumors of the Spine study; ClinicalTrials.gov Identifier NCT01643174) by the AO Spine Knowledge Forum Tumor, patients surgically treated for primary tumors of the spine between 1992 and 2012, were retrospectively analyzed from a prospective database of their medical history. Medical history, tumor characteristics, diagnostics, treatments, cross-sectional survival, and local recurrences were analyzed. Sixty-eight cases (32 f; 36 m), at an average age of 18.6 ± 4.7 years …

Myelin Lipid Metabolism And Its Role In Myelination And Myelin Maintenance, Joseph A Barnes-Vélez, Fatma Betul Aksoy Yasar, Jian Hu

Faculty, Staff and Student Publications

Myelin is a specialized cell membrane indispensable for rapid nerve conduction. The high abundance of membrane lipids is one of myelin's salient features that contribute to its unique role as an insulator that electrically isolates nerve fibers across their myelinated surface. The most abundant lipids in myelin include cholesterol, glycosphingolipids, and plasmalogens, each playing critical roles in myelin development as well as function. This review serves to summarize the role of lipid metabolism in myelination and myelin maintenance, as well as the molecular determinants of myelin lipid homeostasis, with an emphasis on findings from genetic models. In addition, the implications …

Impacts Of Dietary Lysine And Crude Protein On Performance, Hepatic And Renal Functions, Biochemical Parameters, And Histomorphology Of Small Intestine, Liver, And Kidney In Broiler Chickens, Mohamed A Mousa, Ahamed S Asman, Reham M J Ali, Ramy K A Sayed, Kamlah A Majrashi, Khloud G Fakiha, Rashed A Alhotan, Shaimaa Selim

Faculty, Staff and Student Publications

The present study aimed to investigate the effects of increasing dietary lysine (Lys) levels with an adequate dietary crude protein (CP) content, as well as the effects of a reduction in dietary CP content with the recommended amino acid (AAs) level, on the performance, blood biochemical parameters, and histomorphology of the duodenum, liver, and kidney in broiler chickens. A total of 500 broiler chickens were randomly distributed into five dietary treatment groups, following a completely randomized design, where, at the beginning, the control group (C) was fed a diet containing the standard CP and Lys levels: 23% CP with 1.44% …

Effects Of Alginate Oligosaccharide On Testosterone-Induced Benign Prostatic Hyperplasia In Orchiectomized Rats, You-Jee Jang, Hye-Yeon Jung, Ju-Yeong Myeong, Kwang Hoon Song, Joseph Kwon, Duwoon Kim, Jae-Il Park

Faculty, Staff and Student Publications

Benign prostatic hyperplasia (BPH) is an age-related disease of the urinary system that affects elderly men. Current treatments for BPH are associated with several adverse effects, thus highlighting the need for alternative agents. Alginate oligosaccharide (AOS), a water-soluble functional oligomer derived from brown algae, inhibits prostate cancer cell proliferation. However, the effects of AOS on BPH and the underlying molecular mechanisms remain unclear. Therefore, here, we aimed to investigate the therapeutic potential of AOS in BPH by using human benign prostatic epithelial cells (BPH-1) and a rat model of testosterone-induced BPH. Treatment with AOS inhibited in vitro and in vivo …

The Sflt-1/Plgf Ratio In Pregnant Patients Affected By Covid-19, Katarzyna Kosinska-Kaczynska, Ewa Malicka, Iwona Szymusik, Norbert Dera, Michal Pruc, Stepan Feduniw, Zubaid Rafique, Lukasz Szarpak

Faculty, Staff and Students Publications

COVID-19 in pregnant women increases the risk of adverse pregnancy outcomes, including preeclampsia. This meta-analysis aimed to examine the effect of SARS-CoV-2 infection on sFlt-1/PIGF ratio during pregnancy. The study was designed as a systematic review and meta-analysis. PubMed, Web of Science, Embase and Cochrane Library were searched for relevant studies reporting the sFlt-1/PlGF ratio in pregnant women with COVID-19. Results were compared using meta-analysis by the Mantel-Haenszel method. A total of 7 studies were included in the analysis. sFlt-1/PlGF ratios between COVID-19 positive vs. negative women were 45.8 ± 50.3 vs. 37.4 ± 22.5, respectively (SMD = 1.76; 95% …

Individual And Combined Antioxidant Activity Of Spices And Spice Phenolics, Mohammad B Hossain, Lubna Ahmed, Anna Belen Martin-Diana, Nigel P Brunton, Catherine Barry-Ryan

Faculty, Staff and Student Publications

The present study investigated the interaction effects (additive, synergistic, and antagonistic) of different groups of spices, their constituent phenolic compounds, and synthetic antioxidants on the total phenol (TP) content and antioxidant activity, as measured by the ferric-reducing antioxidant power (FRAP) of the mixtures. The results showed that there was an additive effect in all the groups studied, except for the group containing turmeric or curcumin. The groups containing turmeric or curcumin showed a moderate synergistic effect. Among the groups of spices, the highest summated TP (50.6 mg GAE/mL) and FRAP (106.2 mg Trolox/mL) values were observed in the group containing …

Glycolysis Regulates Kras Plasma Membrane Localization And Function Through Defined Glycosphingolipids, Junchen Liu, Ransome Van Der Hoeven, Walaa E Kattan, Jeffrey T Chang, Dina Montufar-Solis, Wei Chen, Maurice Wong, Yong Zhou, Carlito B Lebrilla, John F Hancock

Faculty, Staff and Student Publications

Oncogenic KRAS expression generates a metabolic dependency on aerobic glycolysis, known as the Warburg effect. We report an effect of increased glycolytic flux that feeds into glycosphingolipid biosynthesis and is directly linked to KRAS oncogenic function. High resolution imaging and genetic approaches show that a defined subset of outer leaflet glycosphingolipids, including GM3 and SM4, is required to maintain KRAS plasma membrane localization, with GM3 engaging in cross-bilayer coupling to maintain inner leaflet phosphatidylserine content. Thus, glycolysis is critical for KRAS plasma membrane localization and nanoscale spatial organization. Reciprocally oncogenic KRAS selectively upregulates cellular content of these same glycosphingolipids, whose …

4d Lung Mri With High-Isotropic-Resolution Using Half-Spoke (Ute) And Full-Spoke 3d Radial Acquisition And Temporal Compressed Sensing Reconstruction, Can Wu, Guruprasad Krishnamoorthy, Victoria Yu, Ergys Subashi, Andreas Rimner, Ricardo Otazo

Faculty, Staff and Student Publications

Objective:

To develop a respiratory motion-resolved 4D MRI technique with high-isotropic-resolution (1.1 mm) using 3D radial sampling, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for lung cancer imaging.

Approach:

Free-breathing half- and full-spoke 3D golden-angle radial acquisitions were performed on eight healthy volunteers and eight patients with lung tumors of varying size. A back-and-forth k-space ordering between consecutive interleaves of the 3D radial acquisition was performed to minimize eddy current-related artifacts. Data were sorted into respiratory motion states using camera-based motion navigation and 4D images were reconstructed using temporal compressed sensing to reduce scan time. Normalized sharpness indices …

The Impact Of Covid-19 Pandemic Upon Non-Elective Admissions And Surgery At A Safety-Net Hospital, Aurelien Amiot, Jean-Francois Rahier, Filip Baert, Stephane Nahon, Ailsa Hart, Nikos Viazis, Livia Biancone, Eugeni Domenech, Catherine Reenears, Laurent Peyrin-Biroulet, Laurent Beaugerie, Johan Burisch, I-Care Collaborator Group

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: There are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD.

PATIENTS AND METHODS: We prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases.

RESULTS: In total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. …

Inhibition Of Colorectal Cancer Tumorigenesis By Ursolic Acid And Doxorubicin Is Mediated By Targeting The Akt Signaling Pathway And Activating The Hippo Signaling Pathway, Dan Hu, Ruo Yu Meng, Thi Van Nguyen, Ok Hee Chai, Byung Hyun Park, Ju-Seog Lee, Soo Mi Kim

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product‑derived and chemotherapy agents including curcumin combined with 5‑fluorouracil, resveratrol combined with cisplatin and epigallocatechin‑3‑gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The Akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of UA and DOX on the cell proliferation, apoptosis, migration …