Digital Commons Network^™

Clinical Epidemiological Characteristics And Risk Factors For Severity Of Sars-Cov-2 Pneumonia In Pediatric Patients: A Hospital-Based Study In Vietnam, Sang N Nguyen, Lam T Vu, Ha T Nguyen, Giang H Dao, Anh Ngoc T Nguyen

Faculty, Staff and Student Publications

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In …

Reciprocal Relationships Between Stress And Depressive Symptoms: The Essential Role Of The Nucleus Accumbens, Yizhou Ma, Peter Kochunov, Mark D Kvarta, Tara Legates, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Eric L Goldwaser, Heather Bruce, Kathryn S Hatch, Si Gao, Shuo Chen, Ann Summerfelt, Thomas E Nichols, L Elliot Hong

Faculty, Staff and Student Publications

BACKGROUND: Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

METHODS: In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006-2010, age = 55.0 ± 7.5 [40-70] years; second visit: 2014-2019; age = 62.7 ± 7.5 [44-80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and …

Cytokine Release By Microglia Exposed To Neurologic Injury Is Amplified By Lipopolysaccharide, Michael C Scott, Olivia Leblanc, Harper Day, Candice Haase, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Introduction: Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury.

Methods: Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were …

Combined Ion Beam Irradiation Platform And 3d Fluorescence Microscope For Cellular Cancer Research, Andrew D Harken, Naresh T Deoli, Citlali Perez Campos, Brian Ponnaiya, Guy Garty, Grace S Lee, Malte J Casper, Shikhar Dhingra, Wenze Li, Gary W Johnson, Sally A Amundson, Peter W Grabham, Elizabeth M C Hillman, David J Brenner

Faculty, Staff and Student Publications

To improve particle radiotherapy, we need a better understanding of the biology of radiation effects, particularly in heavy ion radiation therapy, where global responses are observed despite energy deposition in only a subset of cells. Here, we integrated a high-speed swept confocally-aligned planar excitation (SCAPE) microscope into a focused ion beam irradiation platform to allow real-time 3D structural and functional imaging of living biological samples during and after irradiation. We demonstrate dynamic imaging of the acute effects of irradiation on 3D cultures of U87 human glioblastoma cells, revealing characteristic changes in cellular movement and intracellular calcium signaling following ionizing irradiation.

Blockade Of Rho-Associated Kinase Prevents Inhibition Of Axon Regeneration Of Peripheral Nerves Induced By Anti-Ganglioside Antibodies, Andrés Berardo, Cristian R Bacaglio, Bárbara B Báez, Rubén Sambuelli, Kazim A Sheikh, Pablo H H Lopez

Faculty, Staff and Student Publications

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon …

Activation Of Cerebral Ras-Related C3 Botulinum Toxin Substrate (Rac) 1 Promotes Post-Ischemic Stroke Functional Recovery In Aged Mice, Fan Bu, Jia-Wei Min, Md Abdur Razzaque, Ahmad El Hamamy, Anthony Patrizz, Li Qi, Akihiko Urayama, Jun Li

Faculty, Staff and Student Publications

Brain functional impairment after stroke is common; however, the molecular mechanisms of post-stroke recovery remain unclear. It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke. Mounting evidence suggests that axonal regeneration and angiogenesis, the major forms of brain plasticity responsible for post-stroke recovery, diminished with advanced age. Previous studies suggest that Ras-related C3 botulinum toxin substrate (Rac) 1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model. Here, we investigated the role of Rac1 signaling in long-term …

How Territoriality And Sociality Influence The Habitat Selection And Movements Of A Large Carnivore, K Whitney Hansen, Nathan Ranc, John Morgan, Neil R Jordan, J Weldon Mcnutt, Alan Wilson, Christopher C Wilmers

Faculty, Staff and Student Publications

While territoriality is one of the key mechanisms influencing carnivore space use, most studies quantify resource selection and movement in the absence of conspecific influence or territorial structure. Our analysis incorporated social information in a resource selection framework to investigate mechanisms of territoriality and intra‐specific competition on the habitat selection of a large, social carnivore. We fit integrated step selection functions to 3‐h GPS data from 12 collared African wild dog packs in the Okavango Delta and estimated selection coefficients using a conditional Poisson likelihood with random effects. Packs selected for their neighbors' 30‐day boundary (defined as their 95% kernel …

Readiness Of Nociceptor Cell Bodies To Generate Spontaneous Activity Results From Background Activity Of Diverse Ion Channels And High Input Resistance, Jinbin Tian, Alexis G Bavencoffe, Michael X Zhu, Edgar T Walters

Faculty, Staff and Student Publications

Nociceptor cell bodies generate "spontaneous" discharge that can promote ongoing pain in persistent pain conditions. Little is known about the underlying mechanisms. Recordings from nociceptor cell bodies (somata) dissociated from rodent and human dorsal root ganglia have shown that previous pain in vivo is associated with low-frequency discharge controlled by irregular depolarizing spontaneous fluctuations of membrane potential (DSFs), likely produced by transient inward currents across the somal input resistance. Using mouse nociceptors, we show that DSFs are associated with high somal input resistance over a wide range of membrane potentials, including depolarized levels where DSFs approach action potential (AP) threshold. …

Rfx Transcription Factor In The Human-Associated Yeast Candida Albicans Regulates Adhesion To Oral Epithelium, Diana L Rodríguez, Elena Lindemann-Perez, J Christian Perez

Faculty, Staff and Student Publications

Adhesion to mucosal surfaces is a critical step in many bacterial and fungal infections. Here, using a mouse model of oral infection by the human fungal pathobiont Candida albicans, we report the identification of a novel regulator of C. albicans adhesion to the oral mucosa. The regulator is a member of the regulatory factor X (RFX) family of transcription factors, which control cellular processes ranging from genome integrity in model yeasts to tissue differentiation in vertebrates. Mice infected with the C. albicans rfx1 deletion mutant displayed increased fungal burden in tongues compared to animals infected with the reference strain. High-resolution …

4r-Cembranoid Suppresses Glial Cells Inflammatory Phenotypes And Prevents Hippocampal Neuronal Loss In Lps-Treated Mice, Luis A Rojas-Colón, John B Redell, Pramod K Dash, Pedro E Vegas, Wanda Vélez-Torres

Faculty, Staff and Student Publications

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for …

Tavr In Older Adults, Abdulla A Damluji, Gwen Bernacki, Jonathan Afilalo, Radmila Lyubarova, Ariela R Orkaby, Min Ji Kwak, Scott Hummel, James N Kirkpatrick, Mathew S Maurer, Nanette Wenger, Michael W Rich, Dae Hyun Kim, Roberta Y Wang, Daniel E Forman, Ashok Krishnaswami

Faculty, Staff and Student Publications

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. …

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Dietary Magnesium Replacement For Prevention Of Hypomagnesemia In Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy, Wenli Liu, Larissa Meyer, Meroë Morse, Yisheng Li, Juhee Song, Rosalinda Engle, Gabriel Lopez, Santhosshi Narayanan, Pamela T Soliman, Lois Ramondetta, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Purpose: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment.

Materials and methods: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined …

Chromatin Remodeling In Patient-Derived Colorectal Cancer Models, Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar, Shree Bose, Nicholas Giroux, Shengli Ding, Lihua Wang, Jorge Prado Balcazar, Qiang Huang, Pasupathi Sundaramoorthy, Rui Xi, Shannon Jones Mccall, Zhaohui Wang, Chongming Jiang, Yubin Kang, Scott Kopetz, Gregory E Crawford, Steven M Lipkin, Xiao-Fan Wang, Hans Clevers, David Hsu, Xiling Shen

Faculty, Staff and Student Publications

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors …

Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-To-Neuron Transmission, Chan Chen, Ramhari Kumbhar, Hu Wang, Xiuli Yang, Kundlik Gadhave, Cyrus Rastegar, Yasuyoshi Kimura, Adam Behensky, Sumasri Kotha, Grace Kuo, Sruthi Katakam, Deok Jeong, Liang Wang, Anthony Wang, Rong Chen, Shu Zhang, Lingtao Jin, Creg J Workman, Dario A A Vignali, Olga Pletinkova, Hongpeng Jia, Weiyi Peng, David W Nauen, Philip C Wong, Javier Redding-Ochoa, Juan C Troncoso, Mingyao Ying, Valina L Dawson, Ted M Dawson, Xiaobo Mao

Faculty, Staff and Student Publications

The spread of prion-like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion-like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it …

Association Of Hematological And Biochemical Parameters And Hla-Drb1 Alleles With Anti-Cyclic Citrullinated Peptide Autoantibodies In Sudanese Rheumatic Patients, Khalid E Khalid

Faculty, Staff and Student Publications

Introduction

Anti-citrullinated protein/peptide antibodies (ACPA) are crucial for the diagnosis and prognosis of rheumatoid arthritis (RA) and are associated with class II HLA-DRB1 alleles.

The study’s goal was to determine how DRB1 alleles and hematological and biochemical parameters affect ACPA production in RA patients from Sudan.

Methods

The study analyzed the hematological and biochemical parameters and the frequency of HLA-DRB1 alleles in 120 RA patients and 100 controls. Automated analyzers, ELISA, the latex agglutination test, and the Westergren method were utilized for hematological and biochemical testing. HLA class II alleles were genotyped using polymerase chain reaction-sequence-specific primers (PCR-SSP). The student’s …

Evaluating The Readability Of Online Blood Cancer Education Materials Across Different Readability Measures, Ashley Shin, Surbhi Banubakode, Sara Taveras Alam, Anneliese O Gonzalez

Faculty, Staff and Student Publications

Introduction The National Institutes of Health and the American Medical Association recommend patient education materials (EMs) be at or below the sixth-grade reading level. The American Cancer Society, Leukemia & Lymphoma Society, and National Comprehensive Cancer Network have accurate blood cancer EMs. Methods One hundred one (101) blood cancer EMs from the above organizations were assessed using the following: Flesch Reading Ease Formula (FREF), Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Simple Measure of Gobbledygook Index (SMOG), and the Coleman-Liau Index (CLI). Results Only 3.96% of patient EMs scored at or below the seventh-grade reading level in all modalities. …

Lamina Cribrosa Insertions Into The Sclera Are Sparser, Narrower, And More Slanted In The Anterior Lamina, Fengting Ji, Mohammad R. Islam, Bingrui Wang, Yi Hua, Ian A. Sigal

Mechanical Engineering Faculty Publications

Purpose: The lamina cribrosa (LC) depends on the sclera for support. The support must be provided through the LC insertions. Although a continuous insertion over the whole LC periphery is often assumed, LC insertions are actually discrete locations where LC collagenous beams meet the sclera. We hypothesized that LC insertions vary in number, size, and shape by quadrant and depth.

Methods: Coronal cryosections through the full LCs from six healthy monkey eyes were imaged using instant polarized light microscopy. The images were registered into a stack, on which we manually marked LC insertion outlines, nothing their position in-depth and quadrant …

Vascular Complications And Outcomes Following Transcatheter Aortic Valve Replacement In Patients On Chronic Steroid Therapy: A Meta-Analysis, Song Peng Ang, Jia Ee Chia, Vikash Jaiswal, Muhammad Hanif, Ananya Vadhera, Sudarshan Gautam, Anuradha Raut, Saira Rafaqat, Vamsikalayan Borra, Harshwardhan Khandait

School of Medicine Publications

Background: Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported.

Objective: The authors aimed to compare the rate of vascular complications and outcomes between patients with and without CS use after TAVR.

Methods: The authors conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects …

Investigation Of Potential Gut Health Biomarkers In Broiler Chicks Challenged By Campylobacter Jejuni And Submitted To A Continuous Water Disinfection Program, Tilemachos Mantzios, Despoina E. Kiousi, Georgia D. Brellou, Georgios A. Papadopoulos, Vangelis Economou, Marili Vasilogianni, Elisavet Kanari, Evanthia Petridou, Ilias Giannenas, Guillermo Tellez-Isaias, Aglaia Pappa, Alex Galanis, Vasilios Tsiouris

Poultry Science Faculty Publications and Presentations

The exploration of novel biomarkers to assess poultry health is of paramount importance, not only to enhance our understanding of the pathogenicity of zoonotic agents but also to evaluate the efficacy of novel treatments as alternatives to antibiotics. The present study aimed to investigate potential gut health biomarkers in broiler chicks challenged by Campylobacter jejuni and subjected to a continuous water disinfection program. A total of 144 one-day-old hatched broiler chicks were randomly allocated to four treatment groups with four replicates each, according to the following experimental design: Group A received untreated drinking water; Group B received drinking water treated …

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 …

Glial Lipid Droplets Resolve Ros During Sleep, Lindsey D Goodman, Matthew J Moulton, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The Sehgal lab presents data showing that the non-cell autonomous pathway of glial lipid droplet formation occurs during sleep and helps to resolve neuronal reactive oxygen species (ROS). This promotes neuronal function after an active day. Hence, this pathway has an important physiological function beyond its previously described role in ROS-associated diseases, including Alzheimer’s disease.

Signaling Mechanisms Underlying Activity-Dependent Integration Of Adult-Born Neurons In The Mouse Olfactory Bulb, Suyang Bao, Juan M Romero, Benjamin D W Belfort, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Adult neurogenesis has fascinated the field of neuroscience for decades given the prospects of harnessing mechanisms that facilitate the rewiring and/or replacement of adult brain tissue. The subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle are the two main areas in the brain that exhibit ongoing neurogenesis. Of these, adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and continued circuit integration within adult brain tissue. This review focuses on some of the recognized molecular and signaling …

Influence Of Polymeric Microparticle Size And Loading Concentration On 3d Printing Accuracy And Degradation Behavior Of Composite Scaffolds, Gerry L Koons, Panayiotis D Kontoyiannis, Luis Diaz-Gomez, Selma Z Elsarrag, David W Scott, Mani Diba, Antonios G Mikos

Faculty, Staff and Students Publications

Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, …

The Satb1-Mir22-Gba Axis Mediates Glucocerebroside Accumulation Inducing A Cellular Senescence-Like Phenotype In Dopaminergic Neurons, Taylor Russo, Benjamin Kolisnyk, Aswathy B S, Jonathan Plessis-Belair, Tae Wan Kim, Jacqueline Martin, Jason Ni, Jordan A Pearson, Emily J Park, Roger B Sher, Lorenz Studer, Markus Riessland

Faculty, Staff and Students Publications

Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway. Our findings indicate that dysregulation of this pathway leads to the upregulation of glucocerebrosides (GluCer), which triggers a cellular senescence-like phenotype …

A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang

Faculty, Staff and Students Publications

Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. …

Autophagy Is Required For Stem-Cell-Mediated Endometrial Programming And The Establishment Of Pregnancy, Pooja Popli, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Autophagy plays an important role in the normal growth and morphogenesis of a variety of tissues. Its role in uterine maturation, however, is not fully characterized. Recently, we reported that BECN1 (Beclin1)-dependent autophagy, but not apoptosis, is crucial for stem cell-mediated endometrial programming and the establishment of pregnancy in mice. Upon genetic and pharmacological inhibition of BECN1-mediated autophagy, female mice displayed severe endometrial structural and functional defects leading to infertility. Specifically, conditional loss of Becn1 in the uterus induces apoptosis and results in the gradual loss of endometrial progenitor stem cells. Importantly, the restoration of BECN1-driven autophagy, but not apoptosis …

Bringing Proteomics To Bear On Male Fertility: Key Lessons, Rachel Parkes, Thomas X Garcia

Faculty, Staff and Students Publications

Introduction: Male infertility is a major public health concern globally. Proteomics has revolutionized our comprehension of male fertility by identifying potential infertility biomarkers and reproductive defects. Studies comparing sperm proteome with other male reproductive tissues have the potential to refine fertility diagnostics and guide infertility treatment development.

Areas covered: This review encapsulates literature using proteomic approaches to progress male reproductive biology. Our search methodology included systematic searches of databases such as PubMed, Scopus, and Web of Science for articles up to 2023. Keywords used included 'male fertility proteomics,' 'spermatozoa proteome,' 'testis proteomics,' 'epididymal proteomics,' and 'non-hormonal male contraception.' Inclusion criteria …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Sphingosine-1-Phosphate Inhibition Increases Endoplasmic Reticulum Stress To Enhance Oxaliplatin Sensitivity In Pancreatic Cancer, Zachary Gao, Harinarayanan Janakiraman, Yang Xiao, Sung Wook Kang, Jiangling Dong, Jasmine Choi, Besim Ogretmen, Hyun-Sung Lee, Ernest Ramsay Camp

Faculty, Staff and Students Publications

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer resistant to current therapies, including oxaliplatin (Oxa). Growing evidence supports the ability of cancers to harness sphingolipid metabolism for survival. Sphingosine-1-phosphate (S1P) is an anti-apoptotic, pro-survival mediator that can influence cellular functions such as endoplasmic reticulum (ER) stress. We hypothesize that PDAC drives dysregulated sphingolipid metabolism and that S1P inhibition can enhance ER stress to improve therapeutic response to Oxa in PDAC.

METHODS: RNA sequencing data of sphingolipid mediators from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) datasets were analyzed. Murine and human PDAC cell lines were treated …