Digital Commons Network^™

Special Anatomy Series Imaging Inner Ear Structures With High-Frequency Ultrasound: Application To Physical Rehabilitation Space Medicine, Jeffrey Strakowski, Han Zhang, Millard Reschke, Faye Y Chiou-Tan

Faculty, Staff and Students Publications

OBJECTIVE: The objective of this paper is to document the feasibility of image acquisition, image optimization, and sonographic appearance of the exposed anatomic windows of cadaveric inner ear dissection for purposes of potential future clinical evaluation as part of the developing area of physical and rehabilitation space medicine.

METHODS: Cadaveric dissection of the inner ear was conducted with the goal of exposing areas relevant to vestibular balance. Middle and inner ear structures of 3 human cadavers were imaged with multiple broadband transducers, including emphasis with higher frequency transducers.

RESULTS: The images were best optimized with 17 MHz and 22 MHz …

Engineering Small-Molecule And Protein Drugs For Targeting Bone Tumors, Yixian Wang, Chenhang Wang, Meng Xia, Zeru Tian, Joseph Zhou, Julian Meyer Berger, Xiang H-F Zhang, Han Xiao

Faculty, Staff and Students Publications

Bone cancer is common and severe. Both primary (e.g., osteosarcoma, Ewing sarcoma) and secondary (e.g., metastatic) bone cancers lead to significant health problems and death. Currently, treatments such as chemotherapy, hormone therapy, and radiation therapy are used to treat bone cancer, but they often only shrink or slow tumor growth and do not eliminate cancer completely. The bone microenvironment contributes unique signals that influence cancer growth, immunogenicity, and metastasis. Traditional cancer therapies have limited effectiveness due to off-target effects and poor distribution on bones. As a result, therapies with improved specificity and efficacy for treating bone tumors are highly needed. …

Mechanisms Driving Fasting-Induced Protection From Genotoxic Injury In The Small Intestine, Kali Deans-Fielder, Timothy Wu, Thanh Nguyen, Sarah To, Yang-Zhe Huang, Steven J Bark, Jason C Mills, Noah F Shroyer

Faculty, Staff and Students Publications

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

Effects Of Serum Potassium On Mortality In Patients With St-Elevation Myocardial Infarction, Colton J Jensen, Jonathan K Nielsen, Matthew M Talbott, Danielle O'Connell, Vivek S Patel, Peyton A Armstrong, Zubaid Rafique, Lillian M Tia, Krishna K Paul, Dietrich V Jehle

Faculty, Staff and Students Publications

Introduction: Disturbances in potassium levels can induce ventricular arrhythmias and heighten mortality in patients with ST-elevation myocardial infarction (STEMI). This study evaluates the influence of sK levels on seven-day mortality and incidence of ventricular arrhythmias in STEMI patients to further improve clinical guidelines and outcomes.

Methods: This retrospective, propensity-matched study analyzed approximately 250,000 acute STEMI patients from 55 major academic medical centers/healthcare organizations (HCOs) in the US Collaborative Network of the TriNetX database. The sK levels recorded on the day of STEMI diagnosis were categorized into four cohorts: sK ≤ 3.4 (hypokalemia), 3.5 ≤ sK ≤ 4.5 (normal-control), 4.6 ≤ …

Selective Cdk7 Inhibition Suppresses Cell Cycle Progression And Myc Signaling While Enhancing Apoptosis In Therapy-Resistant Estrogen Receptor-Positive Breast Cancer, Cristina Guarducci, Agostina Nardone, Douglas Russo, Zsuzsanna Nagy, Capucine Heraud, Albert Grinshpun, Qi Zhang, Allegra Freelander, Mathew Joseph Leventhal, Avery Feit, Gabriella Cohen Feit, Ariel Feiglin, Weihan Liu, Francisco Hermida-Prado, Nikolas Kesten, Wen Ma, Carmine De Angelis, Antonio Morlando, Madison O'Donnell, Sergey Naumenko, Shixia Huang, Quang-Dé Nguyen, Ying Huang, Luca Malorni, Johann S Bergholz, Jean J Zhao, Ernest Fraenkel, Elgene Lim, Rachel Schiff, Geoffrey I Shapiro, Rinath Jeselsohn

Faculty, Staff and Students Publications

Purpose: Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine-resistant ER+ breast cancer models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ breast cancer. Nonetheless, the precise mechanisms responsible for the activity of CDK7i in ER+ breast cancer remain elusive. Herein, we sought to unravel these mechanisms.

Experimental design: We conducted multi-omic analyses in ER+ breast cancer models in vitro and in vivo, including models with different genetic backgrounds. We also performed genome-wide …

Cardiac Conduction Diseases: Understanding The Molecular Mechanisms To Uncover Targets For Future Treatments, Tingting Li, Qussay Marashly, Jitae A Kim, Na Li, Mihail G Chelu

Faculty, Staff and Students Publications

Introduction: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output.

Areas covered: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field.

Expert opinion: Significant advancement has been made in understanding the molecular …

Caenorhabditis Elegans Endorse Bacterial Nanocellulose Fibers As Functional Dietary Fiber Reducing Lipid Markers, Amanda Muñoz-Juan, Adrien Assié, Anna Esteve-Codina, Marta Gut, Núria Benseny-Cases, Buck S Samuel, Esther Dalfó, Anna Laromaine

Faculty, Staff and Students Publications

Bacterial nanocellulose (BNC) is a promising dietary fiber with potential as a functional food additive. We evaluated BNC fibers (BNCf) in the Caenorhabditis elegans model to obtain insight into the BNCf's biointeraction with its gastrointestinal tract while reducing the variables of higher complex animals. BNCf were uptaken and excreted by worms without crossing the intestinal barrier, confirming its biosafety regarding survival rate, reproduction, and aging for concentrations up to 34 μg/ml BNCf. However, a slight decrease in the worms' length was detected. A possible nutrient shortage or stress produced by BNCf was discarded by measuring stress and chemotactic response pathways. …

The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects Of Bile Acids, Sung Ho Lee, Ji Ho Suh, Mi Jeong Heo, Jong Min Choi, Yang Yang, Hyun-Jung Jung, Zhanguo Gao, Yongmei Yu, Sung Yun Jung, Mikhail G Kolonin, Aaron R Cox, Sean M Hartig, Holger K Eltzschig, Cynthia Ju, David D Moore, Kang Ho Kim

Faculty, Staff and Student Publications

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the current study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of diet-induced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared with C57BL/6J control, partly due to the increased energy expenditure. However, when challenged …

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Yukun Tan, Kian Hong Kock, Jun Wang, Xuesen Cheng, Le Min Tan, Kyung Yeon Han, Chung-Chau Hon, Woong-Yang Park, Jay W Shin, Haijing Jin, Yujia Wang, Han Chen, Li Ding, Shyam Prabhakar, Nicholas Navin, Rui Chen, Ken Chen

Faculty, Staff and Student Publications

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …

Age-Related Differences In The Mouse Corneal Epithelial Transcriptome And Their Impact On Corneal Wound Healing, Anmar Abu-Romman, Kaitlin K Scholand, Gowthaman Govindarajan, Zhiyuan Yu, Sonali Pal-Ghosh, Mary A Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.

METHODS: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a …

Sialic Acid-Siglec-E Interactions Regulate The Response Of Neonatal Macrophages To Group B Streptococcus, Sean J Lund, Pamela G B Del Rosario, Asami Honda, Kaitlin J Caoili, Marten A Hoeksema, Victor Nizet, Kathryn A Patras, Lawrence S Prince

Faculty, Staff and Students Publications

The mammalian Siglec receptor sialoadhesin (Siglec1, CD169) confers innate immunity against the encapsulated pathogen group B Streptococcus (GBS). Newborn lung macrophages have lower expression levels of sialoadhesin at birth compared with the postnatal period, increasing their susceptibility to GBS infection. In this study, we investigate the mechanisms regulating sialoadhesin expression in the newborn mouse lung. In both neonatal and adult mice, GBS lung infection reduced Siglec1 expression, potentially delaying acquisition of immunity in neonates. Suppression of Siglec1 expression required interactions between sialic acid on the GBS capsule and the inhibitory host receptor Siglec-E. The Siglec1 gene contains multiple STAT binding …

Circulating Immune Signatures In Chronic Pancreatitis With And Without Preceding Acute Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Dhiraj Yadav, Dana K Andersen, Santhi Swaroop Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Phil A Hart, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons …

Use Of Topical Methylene Blue To Image Nuclear Morphometry With A Low-Cost Scanning Darkfield Microendoscope, Huayu Hou, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Sharmila Anandasabapathy, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

SIGNIFICANCE: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for

AIM: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract.

APPROACH: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and …

Efficacy And Safety Of Endoscopic Submucosal Dissection For Colorectal Dysplasia In Patients With Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Talia F Malik, Vaishnavi Sabesan, Babu P Mohan, Asad Ur Rahman, Mohamed O Othman, Peter V Draganov, Gursimran S Kochhar

Faculty, Staff and Students Publications

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD).

METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity.

RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc …

Impact Of Obesity And Age On Mouse Corneal Innervation At The Epithelial-Stromal Interface, Justin A Courson, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

PURPOSE: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age.

METHODS: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the …

Prospects For Leveraging The Microbiota As Medicine For Hypertension, David J Durgan, Jasenka Zubcevic, Matam Vijay-Kumar, Tao Yang, Ishan Manandhar, Sachin Aryal, Rikeish R Muralitharan, Hong-Bao Li, Ying Li, Justine M Abais-Battad, Jennifer L Pluznick, Dominik N Muller, Francine Z Marques, Bina Joe

Faculty, Staff and Students Publications

No abstract provided.

Altered Myocardial Lipid Regulation In Junctophilin-2-Associated Familial Cardiomyopathies, Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens

Faculty, Staff and Students Publications

Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and …

Insulin Signal Transduction Mediates Ethanol-Induced Feeding Dysfunction In A Fly Model Of Fetal Alcohol Spectrum Disorder, Manae Matsubara

McNair Research Journal SJSU

No abstract provided.

Genetic And Serological Markers In Colorectal Cancer Surgery, Adrian Silaghi, Vlad Denis Constantin, Dragos Serban, Dragos Epistatu, Ioana Paunica, Daniela Gabriela Bălan, Laura Florentina Rebegea

Journal of Mind and Medical Sciences

Colon cancer is relatively asymptomatic in the early stages, the manifestations appearing and intensifying with the evolution of the disease, especially when associated with local and/or systemic complications. In such cases, surgical interventions are often emergency and involve more extensive operations (on metabolically and immune-stressed organisms), so that an early diagnosis (endoscopy, tumor markers, etc.) remains not only desirable but even a priority, especially in predisposed patients (genetic factors, lifestyle, etc.). As a consequence, the involvement of tumor markers in colon neoplasms has become more and more investigated in recent times. This review investigates the roles of serological and genetic …

Bmp4 And Grem1 Are Targets Of Shh Signaling And Downstream Regulators Of Collagen In The Penis, Jiangping Deng, Timothy Searl, Samuel Ohlander, Danuta Dynda, Daniel A Harrington, Kevin T Mcvary, Carol A Podlasek

Faculty, Staff and Student Publications

Background: Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment.

Aim: We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and …

Quorum-Sensing Agr System Of Staphylococcus Aureus Primes Gene Expression For Protection From Lethal Oxidative Stress, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Faculty, Staff and Student Publications

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Most Common Symptoms Of Prediabetic And Insulin Resistance In Adults In Saudi Arabia, Hassan Mazzhar Bukhari, Fatoon Mohammed Albuqami, Alanoud Mohammed Asiri, Ghadeer Othman Yatim, Jomana Abdullah Alshareef, Ruba Saeed Alzahrani

Makara Journal of Health Research

Background: The prediabetic stage exhibits common symptoms; hence, the risk of developing diabetes can be reduced by identifying these symptoms in the most affected population. This study aimed to examine the prevalence of the main symptoms of insulin resistance in healthy adults aged 18 years and above.

Methods: A cross-sectional study was conducted on 1,514 Saudi adults using an online questionnaire collected from 13th November 2020 to 23rd March 2021. Data on personal, lifestyle, and common symptoms were gathered, and the main symptoms were presented as frequencies with percentages. Association with insulin resistance was evaluated using the Chi-square …

Investigating The Role Of Diet In Modulating Neuroinflammation In Health And Disease, Rasa Valiauga

Dissertations

An estimated 55 million people worldwide suffer from dementia, with the prevalence expected to drastically increase in the coming years as the population ages. Alzheimer’s disease (AD) is the most common form of dementia and the substantial burden associated with AD has been recognized as a growing public health issue. Despite significant advancements in uncovering the mechanisms which play a role in disease pathology, there is currently no cure or effective treatments. AD is highly complex and multifactorial, with accumulation of misfolded protein, oxidative stress, and inflammation among the numerous etiological processes implicated in disease pathogenesis. While genetic risk factors …

Quorum-Sensing Agr System Of Staphylococcus Aureus Primes Gene Expression For Protection From Lethal Oxidative Stress, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Faculty, Staff and Student Publications

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …

Core Planar Cell Polarity Genes Vangl1 And Vangl2 In Predisposition To Congenital Vertebral Malformations, Xin Feng, Yongyu Ye, Jianan Zhang, Yuanqiang Zhang, Sen Zhao, Judith C W Mak, Nao Otomo, Zhengye Zhao, Yuchen Niu, Yoshiro Yonezawa, Guozhuang Li, Mao Lin, Xiaoxin Li, Prudence Wing Hang Cheung, Kexin Xu, Kazuki Takeda, Shengru Wang, Junjie Xie, Toshiaki Kotani, Vanessa N T Choi, You-Qiang Song, Yang Yang, Keith Dip Kei Luk, Kin Shing Lee, Ziquan Li, Pik Shan Li, Connie Y H Leung, Xiaochen Lin, Xiaolu Wang, Guixing Qiu, Disco (Deciphering Disorders Involving Scoliosis And Comorbidities) Study Group, Kota Watanabe, Japanese Early Onset Scoliosis Research Group, Zhihong Wu, Jennifer E Posey, Shiro Ikegawa, James R Lupski, Jason Pui Yin Cheung, Terry Jianguo Zhang, Bo Gao, Nan Wu

Faculty, Staff and Students Publications

Congenital scoliosis (CS) is the most common congenital spinal disorder caused by congenital vertebral malformations (CVMs), influenced by genetic and environmental factors and exhibiting diverse clinical presentations. Here, we identified the critical roles of Vangl1 and Vangl2, two core components in the Wnt/planar cell polarity (Wnt/PCP) signaling pathway, in vertebral development and in predisposition to CVMs in CS patients. We found that in Vangl mutant mouse models, the CVMs present in a Vangl gene dose- and gestational hypoxia-dependent manner. Our studies reveal a complex etiology of CS and its association with Wnt/PCP signaling.

The Variety Of Mechanosensitive Ion Channels In R/Etinal Neurons, Ji-Jie Pang

Faculty, Staff and Students Publications

Alterations in intraocular and external pressure critically involve the pathogenesis of glaucoma, traumatic retinal injury (TRI), and other retinal disorders, and retinal neurons have been reported to express multiple mechanical-sensitive channels (MSCs) in recent decades. However, the role of MSCs in visual functions and pressure-related retinal conditions has been unclear. This review will focus on the variety and functional significance of the MSCs permeable to K+, Na+, and Ca2+, primarily including the big potassium channel (BK); the two-pore domain potassium channels TRAAK and TREK; Piezo; the epithelial sodium channel (ENaC); and the transient receptor potential channels vanilloid TRPV1, TRPV2, and …

Association Between Monosodium Glutamate Consumption With Changes In Gut Microbiota And Related Metabolic Dysbiosis—A Systematic Review, Hossein Ahangari, Behnam Bahramian, Arezou Khezerlou, Milad Tavassoli, Narges Kiani-Salmi, Vahideh Tarhriz, Ali Ehsani

School of Medicine Faculty Publications

Monosodium glutamate (MSG) is used as a common food additive in some foods. However, based on our search and knowledge, no comprehensive study discussed the effect of MSG on the human gut microbiome. In this study, the effects of MSG on the gut microbiome, liver, and kidney were performed. Data were collected from databases including PubMed, Scopus, Web of Science, and ScienceDirect using the search strategy and keywords. Finally, 14 eligible studies were selected for systematic review. This study provides a new perspective on the effects of MSG on the gut flora, shedding light on the potential relationship between MSG …

Interaction Of High-Fat Diet And Brain Trauma Alters Adipose Tissue Macrophages And Brain Microglia Associated With Exacerbated Cognitive Dysfunction, Rebecca J Henry, James P Barrett, Maria Vaida, Niaz Z Khan, Oleg Makarevich, Rodney M Ritzel, Alan I Faden, Bogdan A Stoica

Faculty, Staff and Student Publications

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular …

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 …