Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Impact Of Sustained Calorie Restriction And Weight Cycling On Body Composition In High-Fat Diet-Fed Male And Female C57bl/6j Mice, Daniel L Smith, Yongbin Yang, Luis M Mestre, Beate Henschel, Erik Parker, Stephanie Dickinson, Amit Patki, David B Allison, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Objective: The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity.

Methods: A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. …

Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research design and methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms …

Suspected Thiamine Deficiency Secondary To Chronic Gastrointestinal Illness: A Case Report, Abigail L. Meckley, Natalie Lagattuta, Elise Gonzalez, Chamonix Kinimaka, Jessica El-Bahri

HCA Healthcare Journal of Medicine

Introduction

Thiamine deficiency, also known as beriberi, is a nutritional disorder caused by a lack of thiamine (vitamin B₁) in the diet. It can occur in 2 forms: dry beriberi, which affects the nervous system, and wet beriberi, which affects the cardiovascular system. Gastrointestinal beriberi is a subtype that affects the digestive system and can lead to multisystem involvement. In the United States (US), thiamine deficiency often arises from chronic malnutrition secondary to alcoholism, known as Wernicke-Korsakoff Syndrome.

Case Presentation

A 45-year-old female with no known past medical history or alcohol use disorder came to the emergency department …

5-Ht Neurons Integrate Gaba And Dopamine Inputs To Regulate Meal Initiation, Kristine M Conde, Hueyzhong Wong, Shuzheng Fang, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Hailan Liu, Na Yin, Jonathan C Bean, Junying Han, Megan E Burt, Sanika V Jossy, Yongjie Yang, Qingchun Tong, Benjamin R Arenkiel, Chunmei Wang, Yang He, Yong Xu

Children’s Nutrition Research Center Staff Publications

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to …

Comprehensive Analysis Of Bulk And Single-Cell Transcriptomic Data Reveals A Novel Signature Associated With Endoplasmic Reticulum Stress, Lipid Metabolism, And Liver Metastasis In Pancreatic Cancer, Xiaohong Liu, Bo Ren, Yuan Fang, Jie Ren, Xing Wang, Minzhi Gu, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy.

METHODS: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO …

Short-Term Effects Of Caffeine Supplementation On Cardiac Dynamics And Anaerobic Strength Output In Collegiate Male Athletes, Tyler Clum, Katelyn Messner, Alyssa Jagger, Caeden Gurganus, Kylie Miller, Rema Suniga

ONU Student Research Colloquium

ABSTRACT. Caffeine, a widely consumed drug, has been shown to significantly increase heart rate (HR) and blood pressure (Geethavani et al., 2014), but had only insignificant changes in these cardiovascular measurements (Alhabeeb et al., 2022); while Matsumara and his colleagues (2023) reported that caffeine decreased 100-meter sprint times indicating that caffeine may improve anaerobic performance. The current study investigated the short-term effects of caffeine on heart rate (HR, beats per minute), blood pressure (mmHg), and 20-yard sprint performance time (seconds; Dashr Sprint Timing System). These parameters were measured in triplicate before and at 45-minutes after caffeine supplementation at a dose …

Evaluating The Effect Of Skipping Ticagrelor Doses And Need For Bolus Doses Upon Treatment Resumption Through Population Pk/Pd Simulation, Hiroyoshi Matsui, Le Thien Truc Pham, Eyob D. Adane

ONU Student Research Colloquium

Ticagrelor (Brilinta (R)) is the first reversibly binding oral P2Y12 receptor antagonist. It is used, mostly in combination with aspirin, in patients with acute coronary syndromes to reduce thrombosis. The manufacturer of ticagrelor recommends discontinuing it at least 5 days before any surgery when possible. While the effect of dose interruptions on the risk of thrombosis is not directly studied, it is important to understand the impact of skipping doses on ticagrelor's PK/PD profile for clinical-decision making. The objectives of the current study were to simulate the impact of therapy interruption on the PK/PD of ticagrelor and examine the need …

Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung

Children’s Nutrition Research Center Staff Publications

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before …

Testosterone Supplementation In Patients With Burn Hypermetabolism, Alexandra Dewitt, Anastasiya Ivanko, Jonathan E. Schoen, Aimee Keating, Herb A. Phelan Iii, Jeffrey E. Carter

School of Medicine Faculty Publications

56th Annual Meeting of the American Burn Association, 2024; April 9 - April 12, 2024; Chicago, IL

Nanocavity-Mediated Purcell Enhancement Of Er In Tio2 Thin Films Grown Via Atomic Layer Deposition, Cheng Ji, Michael T Solomon, Gregory D Grant, Koichi Tanaka, Muchuan Hua, Jianguo Wen, Sagar Kumar Seth, Connor P Horn, Ignas Masiulionis, Manish Kumar Singh, Sean E Sullivan, F Joseph Heremans, David D Awschalom, Supratik Guha, Alan M Dibos

Faculty, Staff and Student Publications

The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon …

Ambiguity In Statistical Analysis Methods And Nonconformity With Prespecified Commitment To Data Sharing In A Cluster Randomized Controlled Trial, Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Deependra K Thapa, Andrew W Brown, Daniel E Kpormegbey, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Evaluating Serum Copper And Kidney Function In A Cohort Of Bariatric Surgery Patients, Katherine Mckeon, Mchael Cook, John Baker, Kyle Lapenna, Hua He, Amanda Anderson, Felicia Rabito

School of Medicine Faculty Publications

Association for Clinical and Translational Science 2024; April 3 - April 5, 2024; Las Vegas, NV

Lac-Phe Mediates The Effects Of Metformin On Food Intake And Body Weight, Shuke Xiao, Veronica L Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D Taylor, Xiuqing Guo, Mark O Goodarzi, Alexis C Wood, Yii-Der Ida Chen, Leslie A Lange, Stephen S Rich, Jerome I Rotter, Clary B Clish, Usman A Tahir, Robert E Gerszten, Mark D Benson, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the …

Total Syntheses Of Hosieines A-C, Jiayang Zhang, Xu Yan, Qing-Bao Zhang, Fang Wang, Bin Yang, Yang Yang

Children’s Nutrition Research Center Staff Publications

The collective total syntheses of (±)-hosieines A-C with a cage-like tetracyclic framework have been realized, which includes the first syntheses of hosieines B-C. The key strategy of the synthesis employs a one-pot domino reaction that involves Cu-catalyzed [3+2] cycloaddition, 1,6-enone formation, and 1,6-aza-Michael addition forming the 5/6/6-aza-tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4-aza-Michael addition reaction to afford the tetracyclic framework.

Comprehensive Analysis Of Transcription Factor-Based Molecular Subtypes And Their Correlation To Clinical Outcomes In Small-Cell Lung Cancer, Sehhoon Park, Tae Hee Hong, Soohyun Hwang, Simon Heeke, Carl M Gay, Jiyeon Kim, Hyun-Ae Jung, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Jong Ho Cho, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Hong Kwan Kim, Lauren Averett Byers, John V Heymach, Yoon-La Choi, Se-Hoon Lee, Keunchil Park

Faculty, Staff and Student Publications

BACKGROUND: Recent studies have reported the predictive and prognostic value of novel transcriptional factor-based molecular subtypes in small-cell lung cancer (SCLC). We conducted an in-depth analysis pairing multi-omics data with immunohistochemistry (IHC) to elucidate the underlying characteristics associated with differences in clinical outcomes between subtypes.

METHODS: IHC (n = 252), target exome sequencing (n = 422), and whole transcriptome sequencing (WTS, n = 189) data generated from 427 patients (86.4% males, 13.6% females) with SCLC were comprehensively analysed. The differences in the mutation profile, gene expression profile, and inflammed signatures were analysed according to the IHC-based molecular subtype.

FINDINGS: IHC-based …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissue, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Trends In Us Public Confidence In Science And Opportunities For Progress, Arthur Lupia, David B Allison, Kathleen Hall Jamieson, Jennifer Heimberg, Magdalena Skipper, Susan M Wolf

Children’s Nutrition Research Center Staff Publications

In recent years, many questions have been raised about whether public confidence in science is changing. To clarify recent trends in the public's confidence and factors that are associated with these feelings, an effort initiated by the National Academies' Strategic Council for Research Excellence, Integrity, and Trust (the Strategic Council) analyzed findings from multiple survey research organizations. The Strategic Council's effort, which began in 2022, found that U.S. public confidence in science, the scientific community, and leaders of scientific communities is high relative to other civic, cultural, and governmental institutions for which researchers regularly collect such data. However, confidence in …

Craniofacial Bone Anomalies Related To Cholesterol Synthesis Defects, Chihiro Iwaya, Akiko Suzuki, Junbo Shim, Aemin Kim, Junichi Iwata

Faculty, Staff and Student Publications

DHCR7 and SC5D are enzymes crucial for cholesterol biosynthesis, and mutations in their genes are associated with developmental disorders, which are characterized by craniofacial deformities. We have recently reported that a loss of either Dhcr7 or Sc5d results in a failure in osteoblast differentiation. However, it remains unclear to what extent a loss of function in either DHCR7 or SC5D affects craniofacial skeletal formation. Here, using micro computed tomography (μCT), we found that the bone phenotype differs in Dhcr7

Hif Expression In Clear-Cell Renal Cell Carcinoma (Ccrcc) Tumors Of Adults With And Without Obstructive Sleep Apnea (Osa), Olivia Heppell, Carlos Guerra Londono, Nilesh Gupta

Medical Student Research Symposium

Introduction: Upregulation of hypoxia-inducible factors (HIF) is an important pathological feature shared by clear cell renal cell carcinoma (ccRCC) and obstructive sleep apnea (OSA). However, it is unclear whether OSA alters the pathogenesis of ccRCC via HIF expression.

Methods: A retrospective cohort of adults undergoing nephrectomy for ccRCC was identified electronically (IRB#16040-1). The diagnosis of OSA was established with preoperative STOP-BANG scores or polysomnography. A consecutive sample of 20 individuals with and 20 without OSA was selected. Clinical characteristics and pathology results were reviewed. Resected tumor sections were immunohistochemically stained for HIF-1& HIF-2 at antibody dilutions of 1:150. Intensity and …

A Novel System To Culture Human Intestinal Organoids Under Physiological Oxygen Content To Study Microbial-Host Interaction, Tatiana Y. Fofanova, Umesh C. Karandikar, Jennifer M. Auchtung, Reid L. Wilson, Antonio J. Valentin, Robert A. Britton, K. Jane Grande-Allen, Mary K. Estes, Kristi Hoffman, Sashirekha Ramani, Christopher J. Stewart, Joseph F. Petrosino

Food for Health: Publications

Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen …

The Fatigue-Inducing Effects Of Cancer And Its Therapy Are Characterized By Decreased Physical Activity In The Absence Of Any Motivational Deficit, Thien T Phan, Kiersten S Scott, Brandon Chelette, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Although cancer and its therapy are well known to be associated with fatigue, the exact nature of cancer-related fatigue remains ill-defined. We previously reported that fatigue-like behavior induced independently by tumor growth and by the chemotherapeutic agent cisplatin is characterized by reduced voluntary wheel running and an intact motivation to expand effort for food rewards. The present set of experiments was initiated to characterize the functional consequences of fatigue induced by chemoradiotherapy in tumor-bearing mice and relate them to changes in the expression of genes coding for inflammation, mitochondria dynamics and metabolism. Two syngeneic murine models of cancer were selected …

Omics-Based Profiles And Biomarkers Of Respiratory Infections: Are We There Yet?, Jezreel Pantaleon Garcia, Scott E Evans

Faculty, Staff and Student Publications

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsvL

International Consensus Statement On The Radiological Evaluation Of Dysraphic Malformations Of The Spine And Spinal Cord, Ankit Balani, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Özgür Öztekin, Valeria Capra, Martin Catala, Andrew J Copp, Neetu Kumar, Navroop Johal, M Zubair Tahir, Dominic Thompson, Dachling Pang, David M Mirsky, Mai-Lan Ho, Thierry A G M Huisman, Andrea Rossi, Kshitij Mankad

Children’s Nutrition Research Center Staff Publications

Dysraphic malformations of the spine and spinal cord (DMSSC) represent a spectrum of common congenital anomalies typically (though not exclusively) affecting the lower spinal segments. These may be responsible for varying degrees of neurologic, orthopedic, and urologic morbidity. With advances in neuroimaging, it is now possible to better diagnose and evaluate these disorders both prenatally and postnatally. Neuroimaging, performed at the right time and with technique optimization, is integral in guiding clinical management. However, the terminology used to describe these lesions has become increasingly confusing, and there is a lack of consensus regarding the essential radiologic features and their clinical …

Parental Age Effects And Rett Syndrome, Xiaolan Fang, Lauren M Baggett, Raymond C Caylor, Alan K Percy, Jeffrey L Neul, Jane B Lane, Daniel G Glaze, Tim A Benke, Eric D Marsh, Kathleen J Motil, Judy O Barrish, Fran E Annese, Steven A Skinner

Children’s Nutrition Research Center Staff Publications

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT. Clinical data including parental age, RTT diagnostic status, and clinical severity are collected from 1226 participants with RTT and confirmed MECP2 variants. Statistical analyses are performed using Student t-test, …

Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Xin Xu, Christina Freeman, Hongzhuang Peng, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang

Faculty, Staff and Student Publications

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Metabolism, Fibrosis, And Apoptosis: The Effect Of Lipids And Their Derivatives On Keloid Formation, Chen-Yu Li, Ru-Xin Xie, Shi-Wei Zhang, Jiao Yun, Ai Zhong, Ying Cen, Jun-Jie Chen

Faculty, Staff and Student Publications

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA …

Circulating Metabolic Profile In Idiopathic Pulmonary Fibrosis: Data From The Ipf-Pro Registry, Ross Summer, Jamie Todd, Megan Neely, L. Jason Lobo, Andrew Namen, L. Kristin Newby, Shirin Shafazand, Sally Suliman, Christian Hesslinger, Sascha Keller, Thomas Leonard, Scott M Palmer, Olga Ilkayeva, Michael Muehlbauer, Christopher Newgard, Jesse Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF.

METHODS: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules. Linear regression was used to compare metabolite and clinical analyte levels between patients with IPF …

Characterization Of Variant Rnas Encapsidated During Bromovirus Infection By High-Throughput Sequencing, Sarah Dexheimer, Nipin Shrestha, Bandana Sharma Chapagain, Jozef J. Bujarski, Yanbin Yin

Food for Health: Publications

Previously, we described the RNA recombinants accumulating in tissues infected with the bromoviruses BMV (Brome mosaic virus) and CCMV (Cowpea chlorotic mottle virus). In this work, we characterize the recombinants encapsidated inside the purified virion particles of BMV and CCMV. By using a tool called the Viral Recombination Mapper (ViReMa) that detects recombination junctions, we analyzed a high number of high-throughput sequencing (HTS) short RNA sequence reads. Over 28% of BMV or CCMV RNA reads did not perfectly map to the viral genomes. ViReMa identified 1.40% and 1.83% of these unmapped reads as the RNA recombinants, respectively, in BMV and …

Bispecific Bcma/Cd24 Car-T Cells Control Multiple Myeloma Growth, Fumou Sun, Yan Cheng, Visanu Wanchai, Wancheng Guo, David Mery, Hongwei Xu, Dongzheng Gai, Eric Siegel, Clyde Bailey, Cody Ashby, Samer Al Hadidi, Carolina Schinke, Sharmilan Thanendrarajan, Yupo Ma, Qing Yi, Robert Z Orlowski, Maurizio Zangari, Frits Van Rhee, Siegfried Janz, Gail Bishop, Guido Tricot, John D Shaughnessy, Fenghuang Zhan

Faculty, Staff and Student Publications

Anti-multiple myeloma B cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies represent a promising treatment strategy with high response rates in myeloma. However, durable cures following anti-BCMA CAR-T cell treatment of myeloma are rare. One potential reason is that a small subset of minimal residual myeloma cells seeds relapse. Residual myeloma cells following BCMA-CAR-T-mediated treatment show less-differentiated features and express stem-like genes, including CD24. CD24-positive myeloma cells represent a large fraction of residual myeloma cells after BCMA-CAR-T therapy. In this work, we develop CD24-CAR-T cells and test their ability to eliminate myeloma cells. We find that CD24-CAR-T cells …