Translational Medical Research Commons^™

Targeting The Prmt5/Nur77 Methylation Axis Enhances Endometrial Decidualization Capacity And Female Fertility In Preclinical Models, Zhiwen Cao, Xinyu Cai, Jie Mei, Na Kong, Yang Liu, Xiaoyue Shen, Min Wu, Xin Zhen, Jianxin Sun, Rong Li, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Defective endometrial decidualization is one major cause of female infertility, yet the underlying mechanisms remain elusive. Here, we identified that protein arginine methyltransferase 5 (PRMT5), which was upregulated during decidualization and by progesterone stimulation, was markedly downregulated in the endometria of patients with recurrent implantation failure (RIF), along with a global reduction of symmetric dimethylarginine (SDMA). Uterine stroma-specific ablation of Prmt5 in mice severely impaired decidualization, leading to infertility. A multiomics analysis in human endometrial stromal cells (EnSCs) revealed that PRMT5 promoted decidualization primarily by catalyzing SDMA at arginine 346 (R346) of the orphan nuclear receptor Nur77, which directs its …

Slc Transporter-Mediated Functional Imaging In Cancer Diagnosis, Lumeng Zhang, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Functional imaging has become an important approach for evaluating tumor physiology in vivo beyond morphologic assessment. Radiotracers used for cancer imaging are designed to mimic endogenous substrates or substrate analogues, and their accumulation can depend on membrane transport, intracellular metabolism, and clearance from normal tissues. Specifically, SLC transporters contribute to tracer uptake and signal formation, linking transporter activity with measurable imaging signals in cancer. While [18F]FDG PET/CT remains the most widely used example of transporter-associated metabolic imaging, SLC transporter-mediated imaging strategies have been developed to assess amino acid transport, sodium-dependent glucose uptake, redox metabolism, lactate exchange, nucleoside metabolism, choline metabolism, …

Decorin Promotes Nascent Proteoglycan Retention In Cartilage Matrix By Strengthening Collagen Ii-Aggrecan Integration, Thomas Li, Gabriela Canziani, Yuchen Liu, Neil Patel, Biao Han, Mingyue Fan, Annie Porter, Bryan Kwok, Chao Wang, Qing Li, David E. Birk, Renato V. Iozzo, Irwin M. Chaiken, X. Lucas Lu, Robert L. Mauck, Lin Han

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cartilage extracellular matrix (ECM), a hydrated collagen II-aggrecan composite, undergoes dynamic turnover during both normal homeostasis and disease-associated remodeling. This study elucidates a crucial role for decorin in promoting the retention and stability of nascent aggrecan within this matrix. By applying bio-orthogonal click-labeling, we demonstrate that loss of decorin accelerates the release of nascent aggrecan under both physiological and inflammatory conditions, without affecting its preferential localization to the pericellular matrix. Conversely, supplementation with exogenous decorin mitigates inflammation-induced loss of nascent aggrecan, supporting its potential as a therapeutic target. At the molecular level, decorin exhibits strong binding affinity for aggrecan, and …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

Mitochondrial Ca2+ Uniporter (Mcu) Variants Form Plasma-Membrane Channels, Iuliia Polina, Jyotsna Mishra, Michael Cypress, Maria Landherr, Nedyalka Valkov, Isabel Chaput, Bridget Nieto, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, Ulrike Mende, Peng Zhang, Bong Sook Jhun, Jin O-Uchi

Center for Translational Medicine Faculty Papers

MCU, originally known as CCDC109A, is widely recognized as the gene responsible for encoding a pore-forming subunit of a Ca2+-selective channel, mitochondrial Ca2+ uniporter complex (mtCUC). While MCU expression is typically highly mitochondrial-specific, we report here a protein variant derived from the MCU gene, termed MCU-S, which lacks the mitochondria-targeting sequence (MTS) and forms a Ca2+-permeable channel outside of mitochondria. The mRNA of MCU-S was ubiquitously expressed in all cell types/tissues tested, with particularly high expression in human platelets. MCU-S protein formed Ca2+ channels at the plasma membrane, which exhibited similar channel properties to those observed in mtCUC. MCU-S channels …

Type-1 Ryanodine Receptor Plays An Important Role In Cardiac Hypertrophy And Heart Failure By Increasing Type-2 Ryanodine Receptor-Mediated Calcium Release, Yong-Xiao Wang, Ed Wilson Santos, Sarahann Mistretta, Yuexing Yuan, Harold A. Singer, Shey-Shing Sheu, Yun-Min Zheng

Center for Translational Medicine Faculty Papers

Type-1 ryanodine receptor (RyR1) is essential for skeletal muscle contraction. This Ca²⁺ release channel is expressed in cardiac myocytes; however, its function remains elusive. Cardiac-specific RyR1 overexpression (OE) mice were generated under the cardiac-specific Myh6 promoter. Cardiac hypertrophy (CH), cardiac functions, and mechanistic changes in RyR1 OE and control (wildtype, WT) mice were assessed using hematoxylin and eosin staining, echocardiography, electrocardiogram, quantitative RT-PCR, Western blotting, [³H]-ryanodine binding assay, confocal microscope, ROS dye Amplex Red and 2′,7′-dichlorofluorescein diacetate. RyR1 OE mice had increased whole heart, left ventricular weight, and left ventricular wall thickness, but decreased cardiac output and …

Hiv Infection, Neurotoxicity, Inflammation, Premature Aging, And Therapeutic Challenges To Plwh: An Overview, Mudit Tyagi, Ulhas P. Naik, Kratika Tyagi, Madhulika Sharma, Gagan Kaushal, Alok Bhushan, Michael Bukrinsky, Priya Tyagi

Department of Medicine Faculty Papers

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. …

Cardiac Sr-Mitochondria Contacts-Impact On Cardiac Physiology And Mitochondrial Fitness, Celia Fernandez-Sanz, Shey-Shing Sheu, Sergio De La Fuente

Center for Translational Medicine Faculty Papers

In adult cardiomyocytes, within the Mitochondrial Associated Membranes (MAMs), the sarcoplasmic reticulum (SR) and mitochondria juxtapose each other, forming a unique and highly repetitive functional structure throughout the cells. These SR-mitochondria contact sites have emerged as critical structures that regulate various physiological processes, including lipid exchange, calcium (Ca²⁺) communication, control of excitation-contraction bioenergetics coupling, and reactive oxygen species (ROS) production. Over the years, several scientific studies have reported the accumulation of diverse proteins within these SR-mitochondria close contacts. Some proteins strategically accumulate in these areas to enhance their function, such as the mitochondrial Ca²⁺ uniporter, while others …

Sarcoplasmic Reticulum-Mitochondria Microdomains: Hugging And Kissing In The Heart, Bong Sook Jhun, Jin O-Uchi, Brian Rhee, Ameneh Ahrari, Nathan Demichaelis, Kye-Im Jeon, David M. Booth, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Endoplasmic reticulum (ER)-mitochondrial (ER-Mito) interface, termed mitochondrial-ER contacts (MERCs), plays significant roles in the maintenance of bioenergetics and basal cell functions via the exchange of lipids, Ca 2 þ , and reactive oxygen species (ROS) in various cell types/tissues. Genetic deletion of mitofusin 2 (Mfn2), one of the key components of ER-Mito tethering, in cardiomy- ocytes (CMs) in vivo revealed the importance of the microdomains between mitochondria and sarcoplasmic reticulum (SR), a dif- ferentiated form of ER in muscle cells, for maintaining normal mitochondrial Ca 2 þ (mtCa 2 þ ) handling and bioenergetics in the adult heart. However, key …

Pilot Survey Of Attitudes Toward Xenotransplantation Among Nursing Students In London, Uk., Daniel Rodger, Luz A. Padilla, Daniel J. Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.

METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

Spatiotemporal Calcium Signaling Patterns Underlying Opposing Effects Of Histamine And Tas2r Agonists In Airway Smooth Muscle, Stanley Conaway, Joshua Richard, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Intracellular calcium (Ca²⁺) release via phospholipase C (PLC) following G-protein-coupled receptor (GPCR) activation is typically linked to membrane depolarization and airway smooth muscle (ASM) contraction. However, recent findings show that bitter taste receptor agonists, such as chloroquine (CQ), induce a paradoxical and potent relaxation response despite activating the Ca²⁺ signaling pathway. This relaxation has been hypothesized to be driven by a distinct compartmentalization of calcium ions toward the cellular periphery, subsequently leading to membrane hyperpolarization, in contrast to the contractile effects of histamine. In this study, we further investigate the spatiotemporal dynamics of Ca²⁺ signaling in …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

Tobacco Smoke Exposure Is A Driver Of Altered Oxidative Stress Response And Immunity In Head And Neck Cancer, Yang Li, Pedram Yadollahi, Fonma N Essien, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Abu Hena Mostafa Kamal, Nagireddy Putluri, Lama M Abdurrahman, Maria E Ruiz Echartea, Keenan J Ernste, Akshar J Trivedi, Jonathan Vazquez-Perez, William H Hudson, William K Decker, Rutulkumar Patel, Abdullah A Osman, Farrah Kheradmand, Stephen Y Lai, Jeffrey N Myers, Heath D Skinner, Cristian Coarfa, Kwangwon Lee, Antrix Jain, Anna Malovannaya, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

Background: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.

Methods: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to …

Roles Of Mir-223 In Platelet Function And High On-Treatment Platelet Reactivity: A Brief Report And Review, Shayan Askari, Lawrence E. Goldfinger

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

OBJECTIVES: In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

METHODS: We have …

Notch3 Deletion Regulates Hiv-1 Gene Expression And Systemic Inflammation To Ameliorate Chronic Kidney Disease, Mackenzie Thornton, Nicole Sommer, Mercedes Mcgonigle, Anil Kumar Ram, Sireesha Yerrathota, Henrietta Ehirim, Aakriti Chaturvedi, Johnny Dinh Phan, Anubhav Chakraborty, V. Praveen Chakravarthi, Sumedha Gunewardena, Mudit Tyagi, Jaya Talreja, Tao Wang, Pravin Singhal, Pamela V. Tran, Timothy A. Fields, Patricio E. Ray, Navneet K. Dhillon, Madhulika Sharma

Center for Translational Medicine Faculty Papers

Anti-retroviral therapy (ART) has decreased human immunodeficiency virus (HIV)-1-associated morbidity. However, despite ART, immune cells remain latently infected, leading to chronic inflammation and HIV-1-associated comorbidities. New strategies are needed to target viral proteins and inflammation. We found activation of Notch3 in renal cells of the HIV-1 transgenic mouse model (HIV-Tg26) and in patients with HIV-associated nephropathy. We hypothesized that targeting NOTCH3 activation constitutes an effective therapy for HIV-related chronic kidney disease. We generated HIV-Tg26 mice with Notch3 knocked out (Tg-N3KO). Compared to HIV-Tg26 mice at 3 months, Tg-N3KO mice showed a marked reduction in renal injury, skin lesions and mortality …

Perinuclear Organelle Trauma At The Nexus Of Cardiomyopathy Pathogenesis Arising From Loss Of Function Lmna Mutation, Jason C. Choi

Center for Translational Medicine Faculty Papers

Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the LMNA gene. Although the hypothesis that NE perturbations from LMNA mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy (LMNA cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific Lmna deletion in vivo in the adult heart. We observed extensive NE perturbations prior to cardiac function deterioration with collateral damage in the …

Contributions Of Pathobiological And Translational Science To Understanding And Managing Ischemic Heart Disease: Progress, Impediments, And Future Directions, L Maximilian Buja

The Texas Heart Institute Journal

Key pathobiological components of ischemic heart disease have been identified as follows: (1) In 1970 to 1973, myocardial infarct size was found to be the primary determinant of prognosis after acute myocardial infarction (AMI); (2) in 1973 to 1989, vulnerable coronary artery plaques were found to predispose individuals to coronary plaque disruption and thrombosis, causing major AMI; (3) in 1972, timely coronary reperfusion was demonstrated to limit the size of evolving AMI but with risk of reperfusion injury; and (4) in 1986, myocardial conditioning was found to be a clinically significant modulator capable of delaying AMI progression. Promising cardioprotective strategies …

Metabolic Shifts In Ratio Of Ucocn To Cocn Toward Bone Resorption Contribute To Age-Dependent Bone Loss In Male Mice, Matthew Bernhard, Obinna Okorie, Wei-Ju Louis Tseng, Mengcun Chen, Julia Danon, Mingshu Cui, Elisabeth Lashbrooks, Yanmei Yang, Bin Wang

Center for Translational Medicine Faculty Papers

The study of the senile osteoporosis in men still lags significantly behind that in women. The changes of protein molecule levels and their relationships with bone loss remain poorly understood. In the present study, we used C57BL/6J male mice at ages from 3 to 24 mo to delineate the mechanisms of aging effects on bone loss. We used the microcomputed tomography, mechanical testing, histomorphometry assays, and detection of serum levels of undercarboxylated osteocalcin (ucOcn) and carboxylated osteocalcin (cOcn) to assess bone mass changes and their relationships with the ratios of ucOcn-to-cOcn in mice from different age groups. The results showed …

Recovery After Human Bone Marrow Mesenchymal Stem Cells (Hbm-Mcs)-Derived Extracellular Vesicles (Evs) Treatment In Post-Mcao Rats Requires Repeated Handling, Yolanda Gomez-Galvez, Malvika Gupta, Mandeep Kaur, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi, Amit K. Srivastava, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form …

Genetic Knock-In Of Eif2ak3 Variants Reveals Differences In Perk Activity In Mouse Liver And Pancreas Under Endoplasmic Reticulum Stress, Shivesh Ghura, Noah R. Beratan, Xinglong Shi, Elena Alvarez-Periel, Sarah E. Bond Newton, Cagla Akay-Espinoza, Kelly L. Jordan-Sciutto

Farber Institute for Neuroscience Staff Papers and Presentations

Common single-nucleotide variants (SNVs) of eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) slightly increase the risk of disorders in the periphery and the central nervous system. EIF2AK3 encodes protein kinase RNA-like endoplasmic reticulum kinase (PERK), a key regulator of ER stress. Three exonic EIF2AK3 SNVs form the PERK-B haplotype, which is present in 28% of the global population. Importantly, the precise impact of these SNVs on PERK activity remains elusive. In this study, we demonstrate that PERK-B SNVs do not alter PERK expression or basal activity in vitro and in the novel triple knock-in mice expressing the exonic …

Inhibiting Endothelial Cell Mst1 Attenuates Acute Lung Injury In Mice, Zhi-Fu Guo, Nopprarat Tongmuang, Chao Li, Chen Zhang, Louis Hu, Daniel Capreri, Mei-Xing Zuo, Ross Summer, Jianxin Sun

Center for Translational Medicine Faculty Papers

Lung endothelium plays a pivotal role in the orchestration of inflammatory responses to acute pulmonary insults. Mammalian sterile 20-like kinase 1 (Mst1) is a serine/threonine kinase that has been shown to play an important role in the regulation of apoptosis, stress responses, and organ growth. This study investigated the role of Mst1 in lung endothelial activation and acute lung injury (ALI). We found that Mst1 was significantly activated in inflamed lung endothelial cells (ECs) and mouse lung tissues. Overexpression of Mst1 promoted nuclear factor κ-B (NF-κB) activation through promoting JNK and p38 activation in lung ECs. Inhibition of Mst1 by …

In Search Of The Locus Coeruleus: Guidelines For Identifying Anatomical Boundaries And Electrophysiological Properties Of The Blue Spot In Mice, Fish, Finches, And Beyond, Amelien Vreven, Gary Aston-Jones, Anthony E Pickering, Gina R Poe, Barry Waterhouse, Nelson K Totah

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of …

Acetaminophen Influences Musculoskeletal Signaling But Not Adaptations To Endurance Exercise Training, Brandon Roberts, Alyssa Geddis, Alexandra Ciuciu, Marinaliz Reynoso, Nikhil Mehta, Alyssa Varanoske, Alyssa Kelley, Raymond Walker, Rigoberto Munoz, Alexander Kolb, Jeffery Staab, Marshall Naimo, Ryan Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% …

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Immune Responses Induced At One Hour Post Cataract Surgery Wounding Of The Chick Lens, Jodirae Dedreu, Morgan Basta, Janice Walker, Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the lens is an avascular tissue with an immune-privileged status, studies have now revealed that there are immune responses specifically linked to the lens. The response to lens injury, such as following cataract surgery, has been shown to involve the activation of the resident immune cell population of the lens and the induction of immunomodulatory factors by the wounded epithelium. However, there has been limited investigation into the immediate response of the lens to wounding, particularly those induced factors that are intrinsic to the lens and its associated resident immune cells. Using an established chick embryo ex vivo cataract …

Epicutaneous Sensitization To The Phytocannabinoid Β-Caryophyllene Induces Pruritic Inflammation, Saadet Inan, Sara J Ward, Citlalli T Baltazar, Gabrielle A. Peruggia, Elham Javed, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at …