Medicine and Health Sciences Commons^™

Development Of A Food Composition Database For The Estimation Of Dietary S-Methyl Cysteine Sulfoxide From Vegetables, Caroline R. Hill, Emma L. Connolly, Armaghan Shafaei, Lois Balmer, Liezhou Zhong, Taulant Muka, Antonietta Hayhoe, Shikha Saha, Richard J. Woodman, Joshua R. Lewis, Jonathan M. Hodgson, Lauren C. Blekkenhorst

Research outputs 2022 to 2026

A food composition database estimating S-methyl cysteine sulfoxide (SMCSO) was created following a systematic literature search. SMCSO data (705 entries) from 19 vegetables were summarised: brassicas (n = 10) and alliums (n = 9). The highest SMCSO in brassicas was reported in Brussels sprouts (median [range]: 318 [68−420] mg/100 g fresh weight (FW)) whilst the lowest was in radish (19 [4–45] mg/100 g FW). Brussels sprouts were almost twice as concentrated in SMCSO as cauliflower, followed by cabbage, kale, broccoli, kohlrabi, swede, Chinese cabbage, and turnips. The alliums highest in SMCSO were Chinese chives (271 [185−413] mg/100 g FW) followed …

Simultaneous Extraction And Quantitative Analysis Of S-Methyl-L-Cysteine Sulfoxide, Sulforaphane And Glucosinolates In Cruciferous Vegetables By Liquid Chromatography Mass Spectrometry, Armaghan Shafaei, Caroline R. Hill, Jonathan M. Hodgson, Lauren C. Blekkenhorst, Mary C. Boyce

Research outputs 2022 to 2026

Sulfur containing compounds including glucosinolates (GLS), sulforaphane (SFN) and S-methyl-L-cysteine sulfoxide (SMCSO) have been proposed to be partly responsible for the beneficial health effects of cruciferous vegetables. As such, greater understanding of their measurements within foods is important to estimate intake in humans and to inform dietary intervention studies. Herein is described a simple and sensitive method for simultaneous analysis of 20 GLS, SFN and SMCSO by liquid chromatography mass spectrometry. Analytes were effectively retained and resolved on an Xbridge C18 column. Detection can be achieved using high resolution or unit resolution mass spectrometry; the latter making the method more …

Investigating The Genetic Makeup Of The Major Histocompatibility Complex (Mhc) In The United Arab Emirates Population Through Next-Generation Sequencing, Nour A. D. Marzouka, Halima Alnaqbi, Amira Al-Aamri, Guan Tay, Habiba Alsafar

Research outputs 2022 to 2026

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the …

Immune Checkpoint Inhibitor Therapy For Advanced Cutaneous Squamous Cell Carcinoma In Australia: A Retrospective Real World Cohort Study, Luke S. Mclean, Annette M. Lim, Mathias Bressel, Jenny Lee, Rahul Ladwa, Alexander D. Guminski, Brett Hughes, Samantha Bowyer, Karen Briscoe, Samuel Harris, Craig Kukard, Rob Zielinski, Muhammad Alamgeer, Matteo Carlino, Jeremy Mo, John J. Park, Muhammad A. Khattak, Fiona Day, Danny Rischin

Research outputs 2022 to 2026

Objectives: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. Study design: Retrospective observational study; review of patient records in fifteen Australian institutions. Setting, participants: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 – 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. Main outcome measures: Best overall response rate (ORR) according to …

Quantitative Comparison Of Presenilin Protein Expression Reveals Greater Activity Of Ps2-Γ-Secretase, Melissa K. Eccles, Nathan Main, Rodrigo Carlessi, Ayeisha M. Armstrong, Miheer Sabale, Brigid Roberts-Mok, Janina E. E. Tirnitz-Parker, Mark Agostino, David Groth, Paul E. Fraser, Giuseppe Verdile

Research outputs 2022 to 2026

γ-secretase processing of amyloid precursor protein (APP) has long been of interest in the pathological progression of Alzheimer's disease (AD) due to its role in the generation of amyloid- . The catalytic component of the enzyme is the presenilins of which there are two homologues, Presenilin-1 (PS1) and Presenilin-2 (PS2). The field has focussed on the PS1 form of this enzyme, as it is typically considered the more active at APP processing. However, much of this work has been completed without appropriate consideration of the specific levels of protein expression of PS1 and PS2. We propose that expression is an …

Clinical-Grade Human Skin-Derived Abcb5+ Mesenchymal Stromal Cells Exert Anti-Apoptotic And Anti-Inflammatory Effects In Vitro And Modulate Mrna Expression In A Cisplatin-Induced Kidney Injury Murine Model, Erika Rendra, Adriana T. Crigna, Cristina Daniele, Carsten Sticht, Maike Cueppers, Mark A. Kluth, Christoph Ganss, Markus H. Frank, Norbert Gretz, Karen Bieback

Research outputs 2022 to 2026

Acute kidney injury (AKI) is characterized by a rapid reduction in renal function and glomerular filtration rate (GFR). The broadly used anti-cancer chemotherapeutic agent cisplatin often induces AKI as an adverse drug side effect. Therapies targeted at the reversal of AKI and its potential progression to chronic kidney disease or end-stage renal disease are currently insufficiently effective. Mesenchymal stromal cells (MSCs) possess diverse immunomodulatory properties that confer upon them significant therapeutic potential for the treatment of diverse inflammatory disorders. Human dermal MSCs expressing ATP-Binding Cassette member B5 (ABCB5) have shown therapeutic efficacy in clinical trials in chronic skin wounds or …

Development Of A Regional Climate Change Model For Aedes Vigilax And Aedes Camptorhynchus (Diptera: Culicidae) In Perth, Western Australia, Kerry Staples, Peter J. Neville, Steven Richardson, Jacques Oosthuizen

Research outputs 2022 to 2026

Mosquito-borne disease is a significant public health issue and within Australia Ross River virus (RRV) is the most reported. This study combines a mechanistic model of mosquito development for two mosquito vectors; Aedes vigilax and Aedes camptorhynchus, with climate projections from three climate models for two Representative Concentration Pathways (RCPs), to examine the possible effects of climate change and sea-level rise on a temperate tidal saltmarsh habitat in Perth, Western Australia. The projections were run under no accretion and accretion scenarios using a known mosquito habitat as a case study. This improves our understanding of the possible implications of sea-level …

Investigation Of Campylobacter Concisus Gastric Epithelial Pathogenicity Using Ags Cells, Christopher Y. M. Luk, Seul A. Lee, Nicholas Naidovski, Fang Liu, Alfred C. Y. Tay, Liang Wang, Stephen Riordan, Li Zhang

Research outputs 2022 to 2026

Campylobacter concisus is an oral bacterium. Recent studies suggest that C. concisus may be involved in human gastric diseases. The mechanisms, however, by which C. concisus causes human gastric diseases have not been investigated. Here we examined the gastric epithelial pathogenicity of C. concisus using a cell culture model. Six C. concisus strains and the human gastric epithelial cell line AGS cells were used. IL-8 produced by AGS cells after incubation with C. concisus was measured using enzyme-linked immunosorbent assay (ELISA), and AGS cell apoptosis was determined by caspase 3/7 activities. The effects of C. concisus on actin arrangement in …

Blastocyst Quality And Reproductive And Perinatal Outcomes: A Multinational Multicentre Observational Study, Haowen Zou, James M. Kemper, Elizabeth R. Hammond, Fengqin Xu, Gensheng Liu, Lintao Xue, Xiaohong Bai, Hongqing Liao, Songguo Xue, Shuqin Zhao, Lan Xia, Jean Scott, Vincent Chapple, Masoud Afnan, Dean E. Morbeck, Ben W. J. Mol, Yanhe Liu, Rui Wang

Research outputs 2022 to 2026

STUDY QUESTION: Does the transfer of single low-grade blastocysts result in acceptable reproductive and perinatal outcomes compared to the transfer of single good-grade blastocysts? SUMMARY ANSWER: The transfer of single low-grade blastocysts resulted in a reduced live birth rate of around 30% (14% for very low-grade blastocysts) compared to 44% for single good-grade blastocysts, but does not lead to more adverse perinatal outcomes. WHAT IS KNOWN ALREADY: It is known that low-grade blastocysts can result in live births. However, the current studies are limited by relatively small sample sizes and single-centre designs. Furthermore, evidence on perinatal outcomes after transferring low-grade …

Genomic Analysis Of Clostridioides Difficile Recovered From Horses In Western Australia, Natasza M. R. Hain-Saunders, Daniel R. Knight, Mieghan Bruce, David Byrne, Thomas V. Riley

Research outputs 2022 to 2026

Clostridioides difficile poses an ongoing threat as a cause of gastrointestinal disease in humans and animals. Traditionally considered a human healthcare-related disease, increases in community-associated C. difficile infection (CDI) and growing evidence of inter-species transmission suggest a wider perspective is required for CDI control. In horses, C. difficile is a major cause of diarrhoea and life-threatening colitis. This study aimed to better understand the epidemiology of CDI in Australian horses and provide insights into the relationships between horse, human and environmental strains. A total of 752 faecal samples from 387 Western Australian horses were collected. C. difficile was isolated from …

Higher Overall Intakes Are The Defining Feature Of Dietary Intakes In Nafld And Compared To The General Population, Catherine Properzi, Leon A. Adams, Johnny Lo, Jill L. Sherriff, Gary P. Jeffrey, Therese A. O’Sullivan

Research outputs 2022 to 2026

We aimed to compare the dietary intakes of Australian patients with non-alcoholic fatty liver disease (NAFLD) to general Australian population intake data and determine whether the intake of any nutrient or food group was able to predict the degree of steatosis. Dietary data from fifty adult patients with NAFLD were compared to intake data from the Australian Health Survey for energy, macronutrients, fat sub-types, alcohol, iron, folate, sugar, fibre, sodium and caffeine. Linear regression models adjusting for potential confounders (age, sex, physical activity and body mass index) were used to examine predictive relationships between hepatic steatosis (quantified via magnetic resonance …

Complete Genome Sequences Of Evolutionary Clade C-Iii Strains Of Clostridioides (Clostridium) Difficile Isolated From The Environment In Western Australia, Nirajmohan Shivaperumal, Natasza M. R. Hain-Saunders, Barbara J. Chang, Thomas V. Riley, Daniel R. Knight

Research outputs 2022 to 2026

Clostridioides (Clostridium) difficile in the environment is thought to contribute to C. difficile infection in community settings. Here, we provide complete genome assemblies for two esculin hydrolysis-negative strains of C. difficile that were isolated from soils in Western Australia; the strains produce white colonies on chromogenic media and belong to evolutionarily divergent clade C-III.

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …

Development Of A Scoring Tool For Australian Rural Food Retail Environments, Tracy L. Schumacher, Carissa A. Alderton, Leanne J. Brown, Susan Heaney, Laura Alston, Katherine Kent, Stephanie L. Godrich

Research outputs 2022 to 2026

Current tools scoring the healthiness of food retail outlets do not reflect outlets found in rural locations. This study aimed to adapt pre-existing Australian scoring tools to represent non-metropolitan areas. Rural nutrition experts were identified, and a modified Delphi technique was used to adapt two pre-existing, food-scoring tools in five iterative stages. Stages included identifying all relevant outlets, providing a description and score for each, ensuring consistency between outlet scores and pre-existing, metro-centric tools, and providing instructions for correct use. Six rural nutrition experts were identified and engaged in the modified Delphi technique. The final tool consisted of 12 categories …

Corrigendum: Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar

Research outputs 2022 to 2026

In the published article, there was an error in the legend for Figure 1 as published. The figure legend did not indicate that it has been adapted from Plowright et al. (2017). Copyright permission was obtained from Springer Nature to adapt Figure 1 from Plowright et al. (2017). The corrected legend appears below. Figure 1. Zoonotic risk distribution, pathway to spillover, and the multimodal role of the determinants of spillover. The zoonotic risk is demonstrated by the accumulated distribution of reservoir hosts and vectors that play a role in the pathway to spillover. The risk of spillover is determined by …

Whole-Genome Sequencing Links Clostridium (Clostridioides) Difficile In A Single Hospital To Diverse Environmental Sources In The Community, Su-Chen Lim, Deirdre Collins, Korakrit Imwattana, Daniel R. Knight, Sicilia Perumalsamy, Natasza M.R. Hain-Saunders, Papanin Putsathit, David Speers, Thomas Riley

Research outputs 2022 to 2026

Aims

To investigate if Clostridium (Clostridioides) difficile infection (CDI), traditionally thought of as hospital-acquired, can be genomically linked to hospital or community environmental sources, and to define possible importation routes from the community to the hospital.

Methods and Results

In 2019, C. difficile was isolated from 89/300 (29.7%) floor and 96/300 (32.0%) shoe sole samples at a tertiary hospital in Western Australia. Non-toxigenic C. difficile ribotype (RT) 010 predominated among floor (96.6%) and shoe sole (73.2%) isolates, while toxigenic RT 014/020 was most prevalent among contemporaneous clinical cases (33.0%) at the hospital. Whole-genome sequencing and high-resolution core genome …

A Most Unusual Tail: Scoliosis In A Wild Australian Skink, And Reported Incidences And Suggested Causes Of Similar Malformations Amongst Squamates, Philip W. Bateman, Robyn Benken, Ryan Glowacki, Robert A. Davis

Research outputs 2022 to 2026

Malformations of vertebrae potentially occur across many taxa, particularly in Testudines, which are susceptible to kyphosis (dorsoventral curvature of the spine). Such malformations may stem from either genetic or environmental origins, and their prevalence and associated impacts on survival remain poorly understood. However, scoliosis (sideways curvature of the spine) is rarely reported and especially so in wild lizards. We report here on the first known case of scoliosis in a wild Australian lizard, the skink Ctenotus fallens, from Perth, Western Australia. This occurrence is the first of 805 individuals captured in a natural population monitored annually for the past 11 …

Comparison Of Flavonoid Intake Assessment Methods Using Usda And Phenol Explorer Databases: Subcohort Diet, Cancer And Health-Next Generations—Max Study, Fabian Lanuza, Nicola P. Bondonno, Raul Zamora-Ros, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Rikard Landberg, Jytte Halkjær, Cristina Andres-Lacueva

Research outputs 2022 to 2026

Flavonoids are bioactive plant compounds that are widely present in the human diet. Estimating flavonoid intake with a high degree of certainty is challenging due to the inherent limitations of dietary questionnaires and food composition databases. This study aimed to evaluate the degree of reliability among flavonoid intakes estimated using four different approaches based on the two most comprehensive flavonoid databases, namely, United States Department of Agriculture (USDA) and Phenol Explorer (PE). In 678 individuals from the MAX study, a subcohort of the Diet, Cancer and Health-Next Generations cohort, dietary data were collected using three 24-h diet recalls over 1 …

Differential Effects Of Speech And Language Therapy And Rtms In Chronic Versus Subacute Post-Stroke Aphasia: Results Of The Northstar-Ca Trial, Anna Zumbansen, Heike Kneifel, Latifa Lazzouni, Anja Ophey, Sandra E. Black, Joyce L. Chen, Dylan Edwards, Thomas Funck, Alexander Erich Hartmann, Wolf Dieter Heiss, Franziska Hildesheim, Sylvain Lanthier, Paul Lespérance, George Mochizuki, Caroline Paquette, Elizabet Rochon, Ilona Rubi-Fessen, Jennie Valles, Susan Wortman-Jutt, Alexander Thiel

Research outputs 2022 to 2026

Background & objective: Contralesional 1-Hz repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis combined with speech-language therapy (SLT) has shown positive results on the recovery of naming in subacute (5–45 days) post-stroke aphasia. NORTHSTAR-CA is an extension of the previously reported NORTHSTAR trial to chronic aphasia (>6 months post-stroke) designed to compare the effectiveness of the same rTMS protocol in both phases. Methods: Sixty-seven patients with left middle cerebral artery infarcts (28 chronic, 39 subacute) were recruited (01-2014 to 07-2019) and randomized to receive rTMS (N = 34) or sham stimulation (N = 33) with SLT for …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 2 – Categorical Bivariate Analysis And Attributable Fractions, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: As the cannabis-cancer relationship remains an important open question epidemiological investigation is warranted to calculate key metrics including Rate Ratios (RR), Attributable Fractions in the Exposed (AFE) and Population Attributable Risks (PAR) to directly compare the implicated case burden between emerging cannabinoids and the established carcinogen tobacco. Methods: SEER*Stat software from Centres for Disease Control was used to access age-standardized state census incidence of 28 cancer types (including “All (non-skin) Cancer”) from National Cancer Institute in US states 2001–2017. Drug exposures taken from the National Survey of Drug Use and Health 2003–2017, response rate 74.1%. Federal seizure data provided …

Geotemporospatial And Causal Inferential Epidemiological Overview And Survey Of Usa Cannabis, Cannabidiol And Cannabinoid Genotoxicity Expressed In Cancer Incidence 2003–2017: Part 3 – Spatiotemporal, Multivariable And Causal Inferential Pathfinding And Exploratory Analyses Of Prostate And Ovarian Cancers, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: The epidemiology of cannabinoid-related cancerogenesis has not been studied with cutting edge epidemiological techniques. Building on earlier bivariate papers in this series we aimed to conduct pathfinding studies to address this gap in two tumours of the reproductive tract, prostate and ovarian cancer. Methods: Age-standardized cancer incidence data for 28 tumour types (including “All (non-skin) Cancer”) was sourced from Centres for Disease Control and National Cancer Institute using SEER*Stat software across US states 2001–2017. Drug exposure was sourced from the nationally representative household survey National Survey of Drug Use and Health conducted annually by the Substance Abuse and Mental …

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced …

Immunoanalytic Investigation Of Grain Proteins Antigenic For Celiac Disease Patients In An Einkorn Collection, Zsófia Birinyi, Dalma Réder, Ádám Diós, Ilma R. Korponay-Szabó, Éva Hunyadi-Gulyás, Christakis George Florides, Angéla Juhász, Gyöngyvér Gell

Research outputs 2022 to 2026

Our study focuses on the complex characterization of a wild and cultivated einkorn collection of the Cereal Gene Bank of Agriculture Research Institute in Hungary, using proteomics, immune analytics and bioinformatics analyses. In a serological ELISA pre-screen of 208 different Triticum monococcum L. ssp. monococcum and Triticum monococcum L. ssp. aegilopoides genotypes with celiac disease samples high diversity was observed in the immune response. Based on the immune analytic results, four genotypes with significantly reduced immune reactivity were selected for detailed proteomics characterization. Our results confirm the benefits of high-throughput/large-scale pre-screening and the use of a complex examination platform to …

Evaluation Of Pd-L1 Expression On Circulating Tumour Cells In Small-Cell Lung Cancer, Emmanuel Acheampong, Afaf Abed, Michael Morici, Isaacs Spencer, Aaron B. Beasley, Samantha Bowyer, Du Bois Asante, Chris Lomma, Weitao Lin, Michael Millward, Elin S. Gray

Research outputs 2022 to 2026

Background: Antibodies against the programmed death-1 (PD-1) receptor and its ligand (PD-L1) have been recently approved for small-cell lung cancer (SCLC) treatment. Circulating tumour cells (CTCs) have emerged as an appealing liquid biopsy candidate that could enhance treatment decision-making in systemic therapy for SCLC patients. Several current technologies enrich CTCs using specific surface epitopes, size, rigidity, or dielectric properties. However, they are hampered by the heterogeneity of the enriched cells from blood samples. Methods: We evaluated two CTC enrichment systems: EpCAM conjugated to magnetic beads and a microfluidic device (Parsortix, Angle plc). PD-L1 expression was evaluated on the isolated CTCs. …

Identifying Gene Network Patterns And Associated Cellular Immune Responses In Children With Or Without Nut Allergy, Khui Hung Lee, Anthony Bosco, Michael O'Sullivan, Yong Song, Jessica Metcalfe, Kan Yu, Benjamin J. Mullins, Richard Loh, Guicheng Zhang

Research outputs 2022 to 2026

Background: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. Methods: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from …

Pparα And Pparγ Activation Is Associated With Pleural Mesothelioma Invasion But Therapeutic Inhibition Is Ineffective, M. Lizeth Orozco Morales, Catherine A. Rinaldi, Emma De Jong, Sally M. Lansley, Joel P. A. Gummer, Bence Olasz, Shabarinath Nambiar, Danika E. Hope, Thomas H. Casey, Y. C. Gary Lee, Connull Leslie, Gareth Nealon, David M. Shackleford, Andrew K. Powell, Marina Grimaldi, Patrick Balaguer, Rachael M. Zemek, Anthony Bosco, Matthew J. Piggott, Alice Vrielink, Richard A. Lake, W. Joost Lesterhuis

Research outputs 2022 to 2026

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma …

Evaluation Of Virtual Screening Strategies For The Identification Of Γ-Secretase Inhibitors And Modulators, Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino

Research outputs 2022 to 2026

γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized …

Genotype-Specific Lesion Growth Rates In Stargardt Disease, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Tina M. Lamey, Terri L. Mclaren, Ian L. Mcallister, Ian J. Constable, John N. De Roach, Fred K. Chen

Research outputs 2014 to 2021

Reported growth rates (GR) of atrophic lesions in Stargardt disease (STGD1) vary widely. In the present study, we report the longitudinal natural history of patients with confirmed bial-lelic ABCA4 mutations from five genotype groups: c.6079C > T, c.[2588G > C;5603A > T], c.3113C > T, c.5882G > A and c.5603A > T. Fundus autofluorescence (AF) 30◦ × 30◦ images were manually seg-mented for boundaries of definitely decreased autofluorescence (DDAF). The primary outcome was the effective radius GR across five genotype groups. The age of DDAF formation in each eye was calculated using the x-intercept of the DDAF effective radius against age. Discordance between age at DDAF …

Clinical Trial Of Abcb5+ Mesenchymal Stem Cells For Recessive Dystrophic Epidermolysis Bullosa, Dimitra Kiritsi, Kathrin Dieter, Elke Niebergall-Roth, Silvia Fluhr, Cristina Daniele, Jasmina Esterlechner, Samar Sadeghi, Seda Ballikaya, Leoni Erdinger, Franziska Schauer, Stella Gewert, Martin Laimer, Johann W. Bauer, Alain Hovnanian, Giovanna Zambruno, May El Hachem, Emmanuelle Bourrat, Maria Papanikolaou, Gabriela Petrof, Sophie Kitzmüller, Christen L. Ebens, Markus H. Frank, Natasha Y. Frank, Christoph Ganss, Anna E. Martinez, John A. Mcgrath, Jakub Tolar, Mark A. Kluth

Research outputs 2014 to 2021

BACKGROUND. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating, and lifethreatening inherited skin fragility disorder that comes about due to a lack of functional type VII collagen, for which no effective therapy exists. ABCB5+ dermal mesenchymal stem cells (ABCB5+ MSCs) possess immunomodulatory, inflammation-dampening, and tissue-healing capacities. In a Col7a1-/-mouse model of RDEB, treatment with ABCB5+ MSCs markedly extended the animals' lifespans. METHODS. In this international, multicentric, single-arm, phase I/IIa clinical trial, 16 patients (aged 4-36 years) enrolled into 4 age cohorts received 3 i.v. infusions of 2 × 106ABCB5+ MSCs/kg on days 0, 17, and 35. Patients were followed …

Genetic Analysis Of Endometriosis And Depression Identifies Shared Loci And Implicates Causal Links With Gastric Mucosa Abnormality, Emmanuel Adewuyi, Divya Mehta, Yadav Sapkota, Asa Auta, Kosuke Yoshihara, Mette Nyegaard, Lyn R. Griffiths, Grant W. Montgomery, Daniel I. Chasman, Dale R. Nyholt

Research outputs 2014 to 2021

Evidence from observational studies indicates that endometriosis and depression often co-occur. However, conflicting evidence exists, and the etiology as well as biological mechanisms underlying their comorbidity remain unknown. Utilizing genome-wide association study (GWAS) data, we comprehensively assessed the relationship between endometriosis and depression. Single nucleotide polymorphism effect concordance analysis (SECA) found a significant genetic overlap between endometriosis and depression (PFsig-permuted = 9.99 × 10−4). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (rG = 0.27, P = 8.85 × 10−27). A meta-analysis of endometriosis and depression GWAS (sample size = …