Digital Commons Network^™

Case Report: Dupilumab Successfully Controls Severe Eczema In A Child With Elevated Ige Levels And Recurrent Skin Infections, Tejas P Joshi, Sara Anvari, Meera R Gupta, Carla M Davis, Joud Hajjar

Faculty, Staff and Students Publications

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and …

Power Washing Pulmonary Alveolar Proteinosis, Tiana R Endicott-Yazdani, Gary S Schwartz, Haiying Zhang, Randall L Rosenblatt, Puneet S Garcha

Faculty, Staff and Students Publications

Pulmonary alveolar proteinosis is an uncommon cause of insidious onset shortness of breath and hypoxemia. It is caused by an accumulation of surfactant within the alveoli. Left untreated, it can be fatal. Standard-of-care treatment is whole-lung lavage; however, in severe cases, the associated hypoxemia can be profound and single-lung ventilation would not be tolerated, potentially preventing a lifesaving treatment. Single cases using veno-venous extracorporeal membrane oxygenation to perform whole-lung lavage have been reported. Here we describe three patients with severe pulmonary alveolar proteinosis who were successfully treated with whole-lung lavage using veno-venous extracorporeal membrane oxygenation for oxygenation support.

Conduction Disorders In The Setting Of Acute Stemi, Kjell Nikus, Yochai Birnbaum, Miquel Fiol-Sala, Jani Rankinen, Antoni Bayés De Luna

Faculty, Staff and Students Publications

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because …

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), Katherine R Shaw, Jennifer M Lynch, George H Balazs, T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypotension : A Systematic Review And Individual Participant-Based Meta-Analysis, Stephen P Juraschek, Jiun-Ruey Hu, Jennifer L Cluett, Anthony Ishak, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Ruth L Coleman, William C Cushman, Barry R Davis, Greg Grandits, Rury R Holman, Edgar R Miller, Ruth Peters, Jan A Staessen, Addison A Taylor, Lutgarde Thijs, Jackson T Wright, Kenneth J Mukamal

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).

PURPOSE: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.

DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.

STUDY SELECTION: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, …

Patient-Perceived Versus Actual Risk Of Cardiovascular Disease And Associated Willingness To Consider And Use Prevention Therapy, Ann Marie Navar, Tracy Y Wang, Shuang Li, Xiaojuan Mi, Zhuokai Li, Jennifer G Robinson, Salim S Virani, Eric D Peterson

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient …

Kv13 Channel Up-Regulation In Peripheral Blood T Lymphocytes Of Patients With Multiple Sclerosis, Ioannis Markakis, Ioannis Charitakis, Christine Beeton, Melpomeni Galani, Elpida Repousi, Stella Aggeloglou, Petros P Sfikakis, Michael W Pennington, K George Chandy, Cornelia Poulopoulou

Faculty, Staff and Students Publications

Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy …

Alpha-Single Chains Of Collagen Type Vi Inhibit The Fibrogenic Effects Of Triple Helical Collagen Vi In Hepatic Stellate Cells, Christian Freise, Hyunho Lee, Christopher Chronowski, Doug Chan, Jessica Cziomer, Martin Rühl, Tarkan Dagdelen, Maik Lösekann, Ulrike Erben, Andre Catic, Werner Tegge, Detlef Schuppan, Rajan Somasundaram, Ergun Sahin

Faculty, Staff and Students Publications

The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat …

Hemoglobin A1c Threshold For Reduction In Bone Turnover In Men With Type 2 Diabetes Mellitus, Sabaa Joad, Elliot Ballato, Fnu Deepika, Giulia Gregori, Alcibiades Leonardo Fleires-Gutierrez, Georgia Colleluori, Lina Aguirre, Rui Chen, Vittoria Russo, Virginia Carolina Fuenmayor Lopez, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Emerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.

METHOD: A cross-sectional analysis of baseline data was obtained from 217 men, ages 35-65, regardless of the presence or absence of hypogonadism or …

Deep Simulation Of Facial Appearance Changes Following Craniomaxillofacial Bony Movements In Orthognathic Surgical Planning, Lei Ma, Daeseung Kim, Chunfeng Lian, Deqiang Xiao, Tianshu Kuang, Qin Liu, Yankun Lang, Hannah H Deng, Jaime Gateno, Ye Wu, Erkun Yang, Michael A K Liebschner, James J Xia, Pew-Thian Yap

Faculty, Staff and Students Publications

Facial appearance changes with the movements of bony segments in orthognathic surgery of patients with craniomaxillofacial (CMF) deformities. Conventional bio-mechanical methods, such as finite element modeling (FEM), for simulating such changes, are labor intensive and computationally expensive, preventing them from being used in clinical settings. To overcome these limitations, we propose a deep learning framework to predict post-operative facial changes. Specifically, FC-Net, a facial appearance change simulation network, is developed to predict the point displacement vectors associated with a facial point cloud. FC-Net learns the point displacements of a pre-operative facial point cloud from the bony movement vectors between pre-operative …

Adipocyte-Specific Ablation Of Pu1 Promotes Energy Expenditure And Ameliorates Metabolic Syndrome In Aging Mice, Ke Yun Chen, Alejandra De Angulo, Xin Guo, Aditya More, Scott A Ochsner, Eduardo Lopez, David Saul, Weijun Pang, Yuxiang Sun, Neil J Mckenna, Qiang Tong

Faculty, Staff and Students Publications

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1^fl/fl (control) and AdipoqCre PU.1^fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy …

Lifestyle Risk Factors, Quality Of Life, And Intervention Preferences Of Barrett's Esophagus Patients: A Prospective Cohort Study, Xiaotao Zhang, Sharmila Anandasabapathy, Julian Abrams, Mohamed Othman, Hoda J Badr

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population.

METHODS: Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported …

The E3 Ligase Traf4 Promotes Igf Signaling By Mediating Atypical Ubiquitination Of Irs-1, Wenjuan Yu, Ramesh Singh, Zhao Wang, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Posttranslational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT …

Long Noncoding Rnas And Their Therapeutic Promise In Diabetic Nephropathy, Juan D Coellar, Jianyin Long, Farhad R Danesh

Faculty, Staff and Students Publications

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main …

Mitochondrial Regulation Of Diabetic Kidney Disease, Daniel L Galvan, Koki Mise, Farhad R Danesh

Faculty, Staff and Students Publications

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement …

The Role Of Neutrophils Against Pythium Insidiosum, Apichaya Sriwarom

Chulalongkorn University Theses and Dissertations (Chula ETD)

Pythium insidiosum (P. insidiosum) is an oomycetes fungus-like microorganism causing pythiosis infection in humans. The zoospores (infective stage) of this pathogen contaminate aquatic environments such as moist soil and swampy area, which is a natural habitiat. Humans are infected with P. insidiosum via cutaneous route which is the main entry of the zoospores. Recent studies have shown that patients with pythiosis shows high morbidity and mortality rates particularly those with hematologic diseases. As neutrophils are the first line of immune defense during fungal infections, this study therefore investigated the activity of neutrophils in response to P. insidiosum. The neutrophil killing …

The Effect Of Xylitol And Erythritol In The Presence Of Sucrose On Single And Mixed-Species Biofilm Of Early Colonizer And Cariogenic Streptococci, Panadda Yuapibanrak

Chulalongkorn University Theses and Dissertations (Chula ETD)

Dental caries is caused by multiple factors. An essential factor is sucrose. Dental caries is the result of an imbalance between early colonizers and cariogenic bacteria in biofilms. Sugar alcohols, xylitol and erythritol, become more popular because they do not cause cavities and are also effective at preventing caries. In everyday life, however, sucrose consumption is unavoidable. Thus, the aim of this study was to investigate the effect of xylitol and erythritol in the presence of sucrose on single- and mixed-species biofilm of early colonizers and cariogenic bacteria. Bacteria were cultured in broth containing 1% sucrose compared to broth containing …

Effects Of Curcumin And B1-6-12 On Alterations In Cell Viability, Oxidative Stress, Expression Of Tight Junction Proteins And Barrier Property Of Endothelial Cell And Pericyte Induced By Cisplatin And Oxaliplatin In Vitro, Amornrat Tothonglor

Chulalongkorn University Theses and Dissertations (Chula ETD)

Cisplatin and oxaliplatin are platinum chemotherapeutic drugs that can cause peripheral neuropathy. Nowadays, the pathogenesis of cisplatin/oxaliplatin-induced neuropathy has not been completely elucidated. Emerging evidence revealed that both drugs cause vascular complications. Both drugs might damage nerve capillaries leading to cisplatin/oxaliplatin-induced neuropathy. The objective of this study is to examine the effect of curcumin and B1-6-12 on cisplatin and oxaliplatin-induced alterations in cell viability, apoptosis (caspase-3), oxidative stress (ROS and GSH/GSSG ratio), expression of tight junction proteins (claudin-5, occludin, ZO-1, and ZO-2), and barrier property in endothelial cell and pericyte in vitro. Human umbilical vein endothelial cell (HUVEC) and human …

Identification Of Shared Neoantigens In Brca1-Related Breast Cancer, Lucksica Ruangapirom

Chulalongkorn University Theses and Dissertations (Chula ETD)

Personalized neoantigen-based cancer vaccine has been shown to be safe and immunogenic in cancer patients; however, the manufacturing process can be costly and brings about delay in treatment. Using off-the-shelf cancer vaccine by targeting shared neoantigen may circumvent these problems. We identified BRCA1-mutated breast cancer as a candidate for shared neoantigens because of its clinical aggressiveness and its genotypic and phenotypic similarities suggesting common somatic mutational events within the group. Therefore, we hypothesized that shared-neoantigen may be identified among BRCA1-related breast cancer and may be used as targets for shared neoantigen vaccine. For analyses, we obtained genome sequencing data of …

Precise Extratemporal Pattern And Intramuscular Distribution Of The Facial Nerve, Sukanya Uruwan

Chulalongkorn University Theses and Dissertations (Chula ETD)

An arborization of the branches of the facial nerve has the most complexity and variability. Moreover, knowledge of the facial nerve has great importance for surgical and non-surgical interventions in the face region. However, few studies have attempted to determine the entire course and pattern of terminal branching of the facial nerve in the extratemporal and intramuscular parts of the face. Therefore, the purpose of this study was to investigate the precise detail of the facial nerve in extratemporal and intramuscular parts. This study was conducted in forty-two hemifaces of embalmed cadavers by conventional dissection, fourteen hemi-faces of embalmed cadavers …

Attenuation Of Chronic Kidney Disease (Ckd) And Uremia Induced Gut-Leakage By Lactobacillus Rhamnosus L34, A Probiotic Derived From Thai Population, In 5/6 Nephrectomy Model Mice; An Experimental Study, Somkanya Tungsanga

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation, and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 (L34) might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6-nephrectomy (5/6 Nx) mice. Methods: At 6 weeks post-5/6 Nx in mice, either L34 (1x106 CFU) or phosphate buffer solution (as 5/6 Nx control) were daily fed for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical …

The Association Of Reproductive Factors And Exogenous Hormone Use With Distal Sensory Neuropathy Among The Us Postmenopausal Women: Results From 1999–2004 Nhanes, Jiayu Li

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Distal sensory neuropathy is a common disorder in the peripheral nervous system. We aimed to investigate the association between reproductive history factors and distal sensory neuropathy among the US postmenopausal women aged 40 years and over. We also explored the heterogeneity of these associations by age. Methods: A cross sectional study was conducted with data from postmenopausal women aged 40 years and over in National Health and Nutrition Examination Survey 1999-2004. Women with diabetes, stroke, cancer, cardiovascular diseases, thyroid disease, liver disease, weak/failing kidneys, or amputation were excluded. Distal sensory neuropathy was measured via 10-gram monofilament test and all …

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Downregulation Of Mir-34a Via Calorie Restriction Regulates Lipid Metabolism In The Liver Of Long-Living Ames Dwarf Mice, Sarah Ashiqueali

Electronic Theses and Dissertations, 2020-2023

Ames dwarf mice (df/df) display delayed aging relative to their normal siblings, living approximately 40-60% longer. As such, investigating the mechanisms that enable these organisms to have superior life expectancies may prove useful in developing therapies to slow aging and deter age-related disease. Nonalcoholic fatty liver disease (NAFLD) is a condition that is characterized by the accumulation of excess adipose tissue in the liver. Interestingly, its prevalence tends to increase with age with an incidence rate of greater than 40% in individuals over the age of 60. Previous studies highlight the potential of calorie restriction (CR) in promoting longevity, but …

Efficacy And Safety Of Once-Daily Vibegron For Treatment Of Overactive Bladder In Patients Aged ≥65 And ≥75 Years: Subpopulation Analysis From The Empowur Randomized, International, Phase Iii Study, Susann Varano, David Staskin, Jeffrey Frankel, Denise Shortino, Rachel Jankowich, Paul N. Mudd

Physician Associate Studies Faculty Publications

Background

Overactive bladder (OAB) is common among older adults. The efficacy and safety of vibegron for the treatment of OAB were demonstrated in the international, phase III EMPOWUR trial. This subpopulation analysis from EMPOWUR assessed the efficacy and safety of vibegron in patients aged ≥ 65 and ≥ 75 years.

Methods

In EMPOWUR, patients with OAB were randomly assigned 5:5:4 to receive once-daily vibegron 75 mg, placebo, or tolterodine 4 mg extended release, respectively, once daily for 12 weeks. Coprimary efficacy endpoints were change from baseline at week 12 in average daily number of micturitions and urge urinary incontinence (UUI) …

Cerebellar Coordination Of Neuronal Communication In Cerebral Cortex, Samuel S Mcafee, Yu Liu, Roy V Sillitoe, Detlef H Heck

Duncan NRI Faculty and Staff Publications

Cognitive processes involve precisely coordinated neuronal communications between multiple cerebral cortical structures in a task specific manner. Rich new evidence now implicates the cerebellum in cognitive functions. There is general agreement that cerebellar cognitive function involves interactions between the cerebellum and cerebral cortical association areas. Traditional views assume reciprocal interactions between one cerebellar and one cerebral cortical site, via closed-loop connections. We offer evidence supporting a new perspective that assigns the cerebellum the role of a coordinator of communication. We propose that the cerebellum participates in cognitive function by modulating the coherence of neuronal oscillations to optimize communications between multiple …

Extracellular Vesicles Released By Human Retinal Pigment Epithelium Mediate Increased Polarised Secretion Of Drusen Proteins In Response To Amd Stressors, Miguel Flores-Bellver, Jason Mighty, Silvia Aparicio-Domingo, Kang V. Li, Cui Shi, Jing Zhou, Hannah Cobb, Patrick Mcgrath, German Michelis, Patricia Lenhart, Ganna Bilousova, Søren Heissel, Michael J. Rudy, Christina Coughlan, Andrew E. Goodspeed, S. Patricia Becerra, Stephen Redenti, M. Valeria Canto-Soler

Publications and Research

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular …

Human Retinal Organoids Release Extracellular Vesicles That Regulate Gene Expression In Target Human Retinal Progenitor Cells, Jing Zhou, Miguel Flores‑Bellver, Jianbo Pan, Alberto Benito‑Martin, Cui Shi, Onyekwere Onwumere, Jason Mighty, Jiang Qian, Xiufeng Zhong, Tasmim Hogue, Baffour Amponsah‑Antwi, Linda Einbond, Rajendra Gharbaran, Hao Wu, Bo‑Juen Chen, Zhiliang Zheng, Tatyana Tchaikovskaya, Xusheng Zhang, Hector Peinado, Maria Valeria Canto‑Soler, Stephen Redenti

Publications and Research

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell‑to‑cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three‑dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC‑derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo‑predicted targetome correlates with Gene Ontology (GO) pathways involved in …

X-Linked Serotonin 2c Receptor Is Associated With A Non-Canonical Pathway For Sudden Unexpected Death In Epilepsy, Cory A Massey, Samantha J Thompson, Ryan W Ostrom, Janice Drabek, Olafur A Sveinsson, Torbjörn Tomson, Elisabeth A Haas, Othon J Mena, Alica M Goldman, Jeffrey L Noebels

Faculty, Staff and Students Publications

Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic …

Secretion Of Von Willebrand Factor And Suppression Of Adamts-13 Activity By Markedly High Concentration Of Ferritin, Dalia A Bashir, Qi Da, Subhashree Pradhan, Nitin Sekhar, Christian Valladolid, Fong Lam, Danielle Guffey, Jordana Goldman, Moreshwar S Desai, Miguel A Cruz, Carl Allen, Trung C Nguyen, K Vinod Vijayan

Faculty, Staff and Students Publications

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). …