Digital Commons Network^™

Hsp90 Inhibitor Auy922 Suppresses Tumor Growth And Modulates Immune Response Through Yap1-Tead Pathway Inhibition In Gastric Cancer, Katsuhiro Yoshimura, Gengyi Zou, Yibo Fan, Kohei Yamashita, Lingzhi Wang, Jingjing Wu, Ruiping Wang, Shan Shao, Ailing W Scott, Jiankang Jin, Melissa Pool Pizzi, Xiaodan Yao, Calena-Abel Brown, Linghua Wang, Qiong Gan, Rebecca E Waters, Feng Yin, Shumei Song, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Heat shock protein 90 (HSP90), a vital chaperone involved in the folding and stabilization of various cellular proteins, regulates key functions in many tumor cells. In the context of gastric adenocarcinoma (GAC), where HSP90's role remains largely unexplored, we aimed to investigate the significance of HSP90 inhibitor, AUY922, in regulating the YAP1/TEAD pathway and its association with the tumor immune microenvironment (TME). Our results showed that AUY922 effectively inhibited GAC aggressiveness in both the invitro and invivo models, induced apoptosis, and cell-cycle arrest. Various functional assays elucidated that AUY922 potently inhibited the expression and interaction among YAP1/TEAD and HSP90, resulting …

Adipose Tissue Deficiency Impairs Transient Lipid Accumulation And Delays Liver Regeneration Following Partial Hepatectomy In Male Seipin Knockout Mice, Qianqian Dong, Ziwei Liu, Yidan Ma, Xin Chen, Xiaowei Wang, Jinye Tang, Kexin Ma, Chenxi Liang, Mengyu Wang, Xiaoqin Wu, Yang Liu, Yaru Zhou, Hongyuan Yang, Mingming Gao

Faculty, Staff and Student Publications

Background: Liver diseases pose significant health challenges, underscoring the importance of understanding liver regeneration mechanisms. Systemic adipose tissue is thought to be a primary source of lipids and energy during this process; however, empirical data on the effects of adipose tissue deficiency are limited. This study investigates the role of adipose tissue in liver regeneration, focusing on transient regeneration-associated steatosis (TRAS) and hepatocyte proliferation using a Seipin knockout mouse model that mimics severe human lipodystrophy. Additionally, the study explores therapeutic strategies through adipose tissue transplantation.

Methods: Male Seipin knockout (Seipin-/-) and wild-type (WT) mice underwent 2/3 partial hepatectomy (PHx). Liver …

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …

Protein Arginine Methyltransferases As Regulators Of Cellular Stress, Julia Zaccarelli-Magalhães, Cristiane Teresinha Citadin, Julia Langman, Drew James Smith, Luiz Henrique Matuguma, Hung Wen Lin, Mariana Sayuri Berto Udo

Faculty, Staff and Student Publications

Arginine modification can be a "switch" to regulate DNA transcription and a post-translational modification via methylation of a variety of cellular targets involved in signal transduction, gene transcription, DNA repair, and mRNA alterations. This consequently can turn downstream biological effectors "on" and "off". Arginine methylation is catalyzed by protein arginine methyltransferases (PRMTs 1-9) in both the nucleus and cytoplasm, and is thought to be involved in many disease processes. However, PRMTs have not been well-documented in the brain and their function as it relates to metabolism, circulation, functional learning and memory are understudied. In this review, we provide a comprehensive …

All Three Supersystems-Nervous, Vascular, And Immune-Contribute To The Cortical Infarcts After Subarachnoid Hemorrhage, Jens P Dreier, Alexander Joerk, Hiroki Uchikawa, Viktor Horst, Coline L Lemale, Helena Radbruch, Devin W Mcbride, Peter Vajkoczy, Ulf C Schneider, Ran Xu

Faculty, Staff and Student Publications

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical …

The Dynamics Of Tubulogenesis In Development And Disease, Adrian Romero, Brandy L Walker, Vanja Krneta-Stankic, Kamryn Gerner-Mauro, Lydia Youmans, Rachel K Miller

Faculty, Staff and Student Publications

Tubes are crucial for the function of many organs in animals given their fundamental roles in transporting and exchanging substances to maintain homeostasis within an organism. Therefore, the development and maintenance of these tube-like structures within organs is a vital process. Tubes can form in diverse ways, and advances in our understanding of the molecular and cellular mechanisms underpinning these different modes of tubulogenesis have significant impacts in many biological contexts, including development and disease. This Review discusses recent progress in understanding developmental mechanisms underlying tube formation.

A Phase 2 Basket Study Of Talabostat, A Small-Molecule Inhibitor Of Dipeptidyl Peptidases, Administered In Combination With Pembrolizumab In Patients With Advanced Solid Cancers, Jibran Ahmed, Filip Janku, Daniel D Karp, Sarina A Piha-Paul, Apostolia M Tsimberidou, Timothy Anthony Yap, Bettzy Stephen, Yali Yang, Serdar Gurses, Qian Liu, Juhee Song, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.

Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and immune RECIST …

Establishment Of The Nichols Strain As The Type Strain Of Treponema Pallidum, Steven J Norris

Faculty, Staff and Student Publications

In this article, it is proposed that the Nichols strain of Treponema pallidum be established as the type strain. T. pallidum was first identified as the causative agent of syphilis in 1905, and the Nichols strain was isolated in 1912 by inoculation of a rabbit with cerebrospinal fluid from a patient with neurosyphilis. The Nichols strain has been maintained by serial passage in rabbits for over a century, and historically most studies of T. pallidum have been conducted using this strain. In recent years, a procedure for continuous in vitro culture of T. pallidum in a tissue culture system has …

Patient Outcomes Following Parasagittal Interlaminar Epidural Steroid Injections For Bilateral Lumbar Radicular Symptoms: Correlation Of Contrast Spread With Symptom Relief, Jamal Hasoon, Omar Viswanath, Alan D Kaye, Alberto Pasqualucci, Giustino Varrassi

Faculty, Staff and Student Publications

Introduction Bilateral lumbar radicular symptoms are commonly treated with interlaminar epidural steroid injections (ILESIs). The parasagittal approach often results in unilateral contrast spread, which may influence the degree of bilateral symptom relief. This study evaluates whether unilateral contrast spread correlates with symptom improvement in both ipsilateral and contralateral symptoms. Methods A retrospective review of six patients with bilateral lumbar radiculopathy secondary to lumbar degenerative disc disease, spondylosis, or disc herniation was conducted. All patients underwent ILESIs using a parasagittal approach. The injectate consisted of bupivacaine, preservative-free normal saline, and triamcinolone. Contrast spread was assessed fluoroscopically, and symptom relief was evaluated …

Non-Invasive Prenatal Screening: Testing Motivations And Decision Making In The Low-Risk Population, Jenna K Lea, Blair K Stevens, Shannon Mulligan, Syed S Hashmi, Rebecca Lunstroth, Meagan G Choates

Faculty, Staff and Student Publications

Non-invasive prenatal screening provides a risk assessment for aneuploidies by utilizing cell-free DNA (cfDNA). It is recommended that cell-free DNA screening (cfDNA screening) be offered to all pregnant people regardless of a priori risk for aneuploidy. In the absence of an increased risk, alternative motives for electing cfDNA screening and different levels of informed decision making may arise. Therefore, our study aimed to characterize low-risk patients' motivations for cfDNA screening election, determine how often informed decisions are being made, and compare motivations between informed and uninformed decision makers. A survey that included a modified, validated measure of informed choice (MMIC) …

Angiotensin-(1-9) Improves The Cardioprotective Effects Of Del Nido Cardioplegia Against Ischemia/Reperfusion Injury, Evelyn Mendoza-Torres, Gina Sanchez, Wendy Rosales, María Clara Ospino, Luis Antonio Díaz-Ariza, Yuliet Montoya, John Bustamante, Jaime A Riquelme, Mario Chiong, Sergio Lavandero

Faculty, Staff and Student Publications

Del Nido cardioplegia (DNC), a blood-and-crystalloid solution containing high and low concentrations of potassium and calcium, respectively, is used as a single-dose antegrade infusion to induce immediate cardiac arrest in the surgery of patients with cardiovascular diseases requiring extracorporeal circulation. Adding cardioprotective molecules may further reduce the damage-triggered ischemia/reperfusion (I/R) injury. Angiotensin-(1-9) (Ang-(1-9)) and angiotensin-(1-7) (Ang-(1-7)), members of the counter-regulatory renin-angiotensin system, have shown cardioprotective effects in cardiac hypertrophy and I/R models. This study aimed to evaluate the effects of Ang-(1-9) and Ang-(1-7), as adjuvants of the DNC, on cardioprotection and ventricular function in isolated rat hearts subjected to I/R …

Nadh-Bound Aif Activates The Mitochondrial Chchd4/Mia40 Chaperone By A Substrate-Mimicry Mechanism, Chris A Brosey, Runze Shen, John A Tainer

Faculty, Staff and Student Publications

Mitochondrial metabolism requires the chaperoned import of disulfide-stabilized proteins via CHCHD4/MIA40 and its enigmatic interaction with oxidoreductase Apoptosis-inducing factor (AIF). By crystallizing human CHCHD4's AIF-interaction domain with an activated AIF dimer, we uncover how NADH allosterically configures AIF to anchor CHCHD4's β-hairpin and histidine-helix motifs to the inner mitochondrial membrane. The structure further reveals a similarity between the AIF-interaction domain and recognition sequences of CHCHD4 substrates. NMR and X-ray scattering (SAXS) solution measurements, mutational analyses, and biochemistry show that the substrate-mimicking AIF-interaction domain shields CHCHD4's redox-sensitive active site. Disrupting this shield critically activates CHCHD4 substrate affinity and chaperone activity. Regulatory-domain …

Hsp90: Bringing It All Together, Georgios Ioannis Karras, Giorgio Colombo, Andrea N Kravats

Faculty, Staff and Student Publications

Heat-shock protein 90 (Hsp90) is an ancient and multifaceted protein-folding machine essential for most organisms. The past 40 years have uncovered remarkable complexity in the regulation and function of Hsp90, which dwarfs most other machines in the cell in sophistication. Here, we propose four analogies to illustrate Hsp90's sophistication: a multifunctional Swiss Army knife, an automobile engine and its controls, a switchboard acting as a hub and directing signals, and an orchestra conductor setting the tempo of a symphony. Although each of these analogies represents some key Hsp90 activities, none of them captures the entirety of Hsp90's complexity. Together, these …

Open-Chest Cardiac Ultrasound-Mediated Imaging With A Vacuum Coupler, Nilesh Mathuria, Krithik Vishwanath, Giorgio Brero, Blake C Fallon, Antonio Martino, Richard C Willson, Carly S Filgueira, Richard R Bouchard

Faculty, Staff and Student Publications

BACKGROUND: A fundamental obstacle for the preclinical development of ultrasound-(US) mediated cardiac imaging remains cardiac motion, which limits interframe correlation during extended acquisition periods.

PURPOSE: To address this need, we present the design and implementation of a 3D-printed vacuum coupler that stabilizes a US transducer on the epicardial surface of the heart for feasibility assessment and development of advanced, cardiac, US-mediated imaging approaches.

METHODS: The vacuum coupler was 3D printed with biocompatible resins and secured with a standard intraoperative suction aspirator. US-mediated imaging (i.e., B-mode and photoacoustic [PA] imaging) was performed in an open-chest porcine model with and without the …

American Society For Gastrointestinal Endoscopy Guideline On The Diagnosis And Management Of Gerd: Methodology And Review Of Evidence, Asge Standards Of Practice Committee, Madhav Desai, Wenly Ruan, Nirav C Thosani, Manuel Amaris, J Stephen Scott, Ahmed Saeed, Barham Abu Dayyeh, Marcia Irene Canto, Wasif Abidi, Omeed Alipour, Stuart K Amateau, Natalie Cosgrove, Sherif E Elhanafi, Nauzer Forbes, Divyanshoo R Kohli, Richard S Kwon, Larissa L Fujii-Lau, Jorge D Machicado, Neil B Marya, Saowanee Ngamruengphong, Swati Pawa, Sunil G Sheth, Nikhil R Thiruvengadam, Bashar J Qumseya

Faculty, Staff and Student Publications

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for strategies to diagnose and manage GERD. This document was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and serves as an update to the prior ASGE guideline on the role of endoscopy in the management of GERD (2014). The updated guideline addresses the indications for endoscopy in patients with GERD, including patients who have undergone sleeve gastrectomy (SG) and peroral endoscopic myotomy (POEM). It also discusses endoscopic evaluation of gastroesophageal junctional integrity comprehensively and uniformly. Important, this guideline discusses …

Preclinical And Clinical-Scale Magnetic Particle Imaging Of Natural Killer Cells: In Vitro And Ex Vivo Demonstration Of Cellular Sensitivity, Resolution, And Quantification, Olivia C Sehl, Yanwen Yang, Ariana R Anjier, Dmitry Nevozhay, Donghang Cheng, Kelvin Guo, Benjamin Fellows, Abdul Rahman Mohtasebzadeh, Erica E Mason, Toby Sanders, Petrina Kim, David Trease, Dimpy Koul, Patrick W Goodwill, Konstantin Sokolov, Max Wintermark, Nancy Gordon, Joan M Greve, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation. Cytolytic activity of labeled versus unlabeled NK-92 cells was assessed after 4 h of co-incubation with medulloblastoma cells (DAOY) or osteosarcoma cells (LM7 or OS17). Labeled NK-92 cells at two different doses (0.5 or 1 × 106) …

Toward A Biological Definition Of Neuronal And Glial Synucleinopathies, Claudio Soto, Brit Mollenhauer, Oskar Hansson, Un Jung Kang, Roy N Alcalay, David Standaert, Claudia Trenkwalder, Kenneth Marek, Douglas Galasko, Kathleen Poston

Faculty, Staff and Student Publications

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms. We underscore the utility of the αSyn seed amplification assay to detect aggregated αSyn in living …

On The Acceptance, Commissioning, And Quality Assurance Of Electron Flash Units, Allison Palmiero, Kevin Liu, Julie Colnot, Nitish Chopra, Denae Neill, Luke Connell, Brett Velasquez, Albert C Koong, Steven H Lin, Peter Balter, Ramesh Tailor, Charlotte Robert, Jean-François Germond, Patrik Gonçalves Jorge, Reiner Geyer, Sam Beddar, Raphael Moeckli, Emil Schüler

Faculty, Staff and Student Publications

Background and purpose: FLASH or ultra-high dose rate (UHDR) radiation therapy (RT) has gained attention in recent years for its ability to spare normal tissues relative to conventional dose rate (CDR) RT in various preclinical trials. However, clinical implementation of this promising treatment option has been limited because of the lack of availability of accelerators capable of delivering UHDR RT. Commercial options are finally reaching the market that produce electron beams with average dose rates of up to 1000 Gy/s. We established a framework for the acceptance, commissioning, and periodic quality assurance (QA) of electron FLASH units and present an …

Sustainable Solutions To The Continuous Threat Of Antimicrobial Resistance, Brad Spellberg, David N Gilbert, Michael Baym, Gonzalo Bearman, Tom Boyles, Arturo Casadevall, Graeme N Forrest, Sarah Freling, Bassam Ghanem, Fergus Hamilton, Brian Luna, Jessica Moore, Daniel M Musher, Travis B Nielsen, Priya Nori, Matthew C Phillips, Liise-Anne Pirofski, Andrew F Shorr, Steven Y C Tong, Todd C Lee, Emily G Mcdonald

Faculty, Staff and Students Publications

To combat antimicrobial resistance (AMR), advocates have called for passage of the Pioneering Antimicrobial Subscriptions To End Upsurging Resistance (PASTEUR) Act in the United States, which would appropriate $6 billion in new taxpayer-funded subsidies for antibiotic development. However, the number of antibiotics in clinical development, and US Food and Drug Administration approvals of new antibiotics, have already markedly increased in the last 15 years. Thus, instead of focusing on more economic subsidies, we recommend reducing selective pressure driving AMR by (1) establishing pay-for-performance mechanisms that disincentivize overprescribing of antibiotics, (2) focusing existing research and development funding on strategies that decrease …

Synaptic Alterations In Pyramidal Cells Following Genetic Manipulation Of Neuronal Excitability In Monkey Prefrontal Cortex, Guillermo Gonzalez-Burgos, Takeaki Miyamae, Yosuke Nishihata, Olga L Krimer, Kirsten Wade, Kenneth N Fish, Dominique Arion, Zhao-Lin Cai, Mingshan Xue, William R Stauffer, David A Lewis

Duncan NRI Faculty and Staff Publications

The primate dorsolateral prefrontal cortex (DLPFC) displays unique in vivo activity patterns, but how in vivo activity regulates DLPFC pyramidal neuron (PN) properties remains unclear. We assessed the effects of in vivo Kir2.1 overexpression, a genetic silencing tool, on synapses in monkey DLPFC PNs. We show for the first time that recombinant ion channel expression successfully modifies the excitability of primate cortex neurons, producing effects on synaptic properties apparently different from those in the rodent cortex.

Association Of Serum Endocannabinoid Levels With Pancreatitis And Pancreatitis-Related Pain, Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli

Faculty, Staff and Student Publications

No abstract provided.

Serotonin 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 orally administered therapeutics. Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using an optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays a role in 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 can be enhanced by hunger. Additionally, …

Leptin Receptor Neurons In The Dorsomedial Hypothalamus Require Distinct Neuronal Subsets For Thermogenesis And Weight Loss, Marie Francois, Laura Kaiser, Yanlin He, Yong Xu, J Michael Salbaum, Sangho Yu, Christopher D Morrison, Hans-Rudolf Berthoud, Heike Münzberg

Children’s Nutrition Research Center Staff Publications

The dorsomedial hypothalamus (DMH) receives inputs from the preoptic area (POA), where ambient temperature mediates physiological adaptations of energy expenditure and food intake. Warm-activated POA neurons suppress energy expenditure via brown adipose tissue (BAT) projecting neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA). Our earlier work identified leptin receptor (Lepr)-expressing, BAT-projecting dDMH/DHA neurons that mediate metabolic leptin effects. Yet, the neurotransmitter (glutamate or GABA) used by dDMH/DHALepr neurons remains unexplored and was investigated in this study using mice. We report that dDMH/DHALepr neurons represent equally glutamatergic and GABAergic neurons. Surprisingly, chemogenetic activation of glutamatergic and/or GABAergic dDMH/DHA neurons were capable …

Revisiting What Constitutes A Neglected Tropical Disease?, Paul J Brindley, Peter J Hotez, Shaden Kamhawi

Center for Medical Ethics and Health Policy Staff Publications

PLOS Neglected Tropical Diseases (PLOS NTDs) publishes research devoted to pathogenesis and other clinical aspects, epidemiology, prevention, diagnosis, treatment, and control of the neglected tropical diseases (NTDs), as well as work relevant to public health policy. We define NTDs as poverty-promoting infectious diseases that can negatively impact the quality of life in rural areas and poor urban areas of low- and middle-income countries but which can also affect specific communities within high-income countries. The poverty-inducing effects of the NTDs operate by impairing child health and development, pregnancy outcomes for both mother and child, worker productivity, and quality of life. The …

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …

Comparative Single-Cell Analysis Reveals Tendon Progenitor Dysfunction By Age-Associated Oxidative Stress And Its Restoration By Antioxidant Treatments, Youngjae Jeong, Dongwook Yang, Jea Giezl Solidum, Laura Ortinau, Dongsu Park

Faculty, Staff and Students Publications

Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/progenitor cells (TSPCs) remain unknown. Here, comparative single cell transcriptomics of early postnatal (2 weeks old) and adult (20 weeks old) mouse tendons revealed that adult tendons have reduced number of TSPCs, decreased gene expression in tendon and cartilage development, and a greater population of fibro-tenogenic cells. Notably, adult TSPCs and tenocytes exhibit increased expression of immune-response and oxidative-stress genes with higher EGFR but decreased IGF signaling. Adult tendon cells show increased …

Corticobasal Syndrome: Are There Central Or Peripheral Triggers?, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

Background and objectives: Corticobasal syndrome (CBS) is a complex of symptoms and signs comprising limb rigidity, bradykinesia, dystonia, myoclonus, apraxia, cortical sensory loss, and a variety of cognitive and language impairments. CBS is commonly seen in tauopathies. Striking asymmetry in clinical and imaging findings in CBS raises questions about potential triggers initiating neurodegeneration. The objective of this study was to investigate potential central or peripheral triggers preceding CBS symptoms.

Methods: In this retrospective observational study, we reviewed medical records of patients with CBS at our Parkinson's Disease Center and Movement Disorders Clinic, focusing on evidence of possible central or peripheral …

Use Of Immunoglobulin Replacement Therapy In Clinical Practice: A Review, Jibran Ahmed, Yeonjoo Choi, Taeyeong Ko, Joann Lim, Joud Hajjar

Faculty, Staff and Students Publications

Immunoglobulins (Igs) are produced by B lymphocytes and play a key role in humoral immunity. Igs are classified into five isotypes (IgG, IgA, IgM, IgE, and IgD). Their primary function is to recognize and bind to foreign antigens. When Igs bind to antigens, they facilitate phagocytosis and promote clearance mediated by other immune cells. It is an essential component in protecting the host from outside pathogens. Hypogammaglobulinemia predisposes an individual to severe and recurrent infections. Therefore, replacement therapy is recommended to maintain optimal Ig level. In addition, Igs can modulate immune responses by to neutralizing proteins such as endotoxins or …

The Efficacy Of Complementary And Alternative Medicines In Medical Dermatology: A Comprehensive Review, Promise Ufomadu, Bartley Joseph Gill, Ida Orengo, Theodore Rosen, Ikue Shimizu

Faculty, Staff and Students Publications

Background: In recent years, there has been a widespread patient use of complementary and alternative medicines (CAMs) for dermatological application, despite few RCT-level studies on these supplements. This creates a barrier for dermatologists and others in counseling patients who may be using or might be tempted to use these CAM agents. This review investigates various CAM modalities used by patients for medical dermatology, exploring their efficacy and toxicity profiles.

Methods: A comprehensive review was performed on the effectiveness of several CAMs utilized in medical dermatology by patients. A literature search was conducted using PubMed, Embase, Google Scholar, Web of Science, …

Unprecedented Female Mutation Bias In The Aye-Aye, A Highly Unusual Lemur From Madagascar, Richard J Wang, Yadira Peña-García, Muthuswamy Raveendran, R Alan Harris, Thuy-Trang Nguyen, Marie-Claude Gingras, Yifan Wu, Lesette Perez, Anne D Yoder, Joe H Simmons, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Every mammal studied to date has been found to have a male mutation bias: male parents transmit more de novo mutations to offspring than female parents, contributing increasingly more mutations with age. Although male-biased mutation has been studied for more than 75 years, its causes are still debated. One obstacle to understanding this pattern is its near universality-without variation in mutation bias, it is difficult to find an underlying cause. Here, we present new data on multiple pedigrees from two primate species: aye-ayes (Daubentonia madagascariensis), a member of the strepsirrhine primates, and olive baboons (Papio anubis). In stark contrast to …