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SARS-CoV-2 spike protein-ACe2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya joanne K.Tobacman Jesse Brown VA Medical Center and University of Illinois at Chicago ChicagoIL 60612USA

Immunostaining in lungs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase(Arylsulfatase B;ARSB).To explain these findings,human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional mechanisms were ***-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11,which contributed to chondroitin sulfate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-e2F1 binding and decline in e2F1 binding to the ARSB *** increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as well as antihistamine desloratadine and antibiotic *** the mouse model of carrageenan-induced systemic inflammation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and declines in DNA-e2F binding and ARSB expression occurred in the lung,similar to theobserved effects in this SPRBD model of COVID-19 *** accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage,increased attention to p38-MAPK inhibition may be beneficial in amelioratingCovid-19infections.

关键词： ACe2 lung inhibited

3D models of dilated cardiomyopathy:Shaping the chemical,physical and topographical properties of biomaterials to mimic the cardiac extracellular matrix

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Bioactive Materials 2022年第1期7卷 275-291页

作者： Marie Camman Pierre joanne Onnik Agbulut Christophe Helary Sorbonne Universit´e CNRSUMR 7574Laboratoire de Chimie de la Matiere Condensee de Paris4 place Jussieu(case 174)F-75005ParisFrance Sorbonne Universite Institut de Biologie Paris-Seine(IBPS)CNRS UMR 8256Inserm ERL U1164Biological Adaptation and Ageing7 quai St-Bernard(case 256)F-75005ParisFrance

The pathophysiology of dilated cardiomyopathy(DCM),one major cause of heart failure,is characterized by the dilation of the heart but remains poorly understood because of the lack of adequate in vitro *** 2D models do not allow for the 3D organotypic organization of cardiomyocytes and do not reproduce the eCM *** this review,the different strategies to mimic the chemical,physical and topographical properties of the cardiac tissue affected by DCM are *** advantages and drawbacks of techniques generating anisotropy required for the cardiomyocytes alignment are *** addition,the different methods creating macroporosity and favoring organotypic organization are ***,the advances in the induced pluripotent stem cells technology to generate cardiac cells from healthy or DCM patients will be *** to the biomaterial design,some features of the DCM extracellular matrix such as stiffness,porosity,topography or chemical changes can impact the cardiomyocytes function in vitro and increase their *** mimicking the affected heart,both at the cellular and at the tissue level,3D models will enable a better understanding of the pathology and favor the discovery of novel therapies.

关键词： Biomaterials Dilated cardiomyopathies Induced pluripotent stem cells Porosity Anisotropy

New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

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World Journal of Gastroenterology 2009年第2期15卷 192-197页

作者： Charles H Knowles joanne e Martin Neurogastroenterology Group Centres for Academic Surgery and Pathology Institute of Cellular and Molecular Science Barts and the London Queen Mary's School of Medicine and Dentistry Whitechapel London United Kingdom

Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this fi eld, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

关键词：肠疾病肠神经疾病间隙细胞内脏疼痛

Innovations in the diagnosis and management of uveitis: promising research to address unmet patient needs

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Annals of eye Science 2022年第1期7卷 1-7页

作者： Steven Yeh Ye Huang joanne Thomas Truhlsen eye Institute University of Nebraska Medical CenterOmahaNEUSA emory eye Center Emory University School of MedicineAtlantaGAUSA Medical College of Georgia AugustaGAUSA.

Uveitis,or inflammation of the uveal tissues(iris,ciliary body and the choroid),and its contiguous structures,can lead to severe visual impairment and is among the leading causes of vision impairment worldwide(1).In clinical practice,specialists in uveitis and ocular immunology are called upon to manage a range of uveitis syndromes-infectious disease,noninfectious autoimmune conditions,and masquerade syndromes such as ***,ophthalmologists of all subspecialties(i.e.,medical and surgical retina,corneal surgeons,orbital/oculoplastic surgeons,and comprehensive ophthalmologists)are called upon to manage uveitis syndromes,emphasizing clear importance to understanding common uveitis syndromes,diagnostic workups,and the state-of-the-art in uveitis and ocular inflammation care.

关键词： uveitis inflammation diagnosis

Targeting uptake transporters for cancer imaging and treatment

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Acta Pharmaceutica Sinica B 2020年第1期10卷 79-90页

作者： Yuchen Zhang joanne Wang Department of Pharmaceutics University of WashingtonSeattleWA 98195USA

Cancer cells reprogram their gene expression to promote growth,survival,proliferation,and *** unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer *** this review,we focus on several solute carrier(SLC)transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells,including the sodium/iodine symporter(NIS),norepinephrine transporter(NeT),glucose transporter 1(GLUT1),and monocarboxylate transporters(MCTs).The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents[e.g.,Ⅰ-123,Ⅰ-131,123Ⅰ-iobenguane(mIBG),18F-fluorodeoxyglucose(18F-FDG)and 13C pyruvate].Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are ***,we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and *** analyzing the few clinically successful examples,we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment.

关键词： Uptake transporter Warburg effect Cancer imaging Neuroblastoma Thyroid cancer mIBG

Mitochondrial dysfunction in Parkinson＇s disease： a possible target for neuroprotection

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Frontiers in Biology 2014年第6期9卷 489-503页

作者： Jacqueline A. GLeAVe Peter D. PeRRI joanne e. NASH Centre for Neurobiology of Stress Department of Biological Sciences University of Toronto Scarborough Toronto Ontario M1C1A4Canada

Mitochondria are dynamic organelles which are required for maintaining cellular homeostasis. Thus, it is not surprising that irregularities in mitochondrial function result in cellular damage and are linked with neurodegenerative diseases, such as Parkinson＇s disease. evidence that mitochondrial dysfunction is key to the pathogenesis of Parkinson＇s disease is founded in studies in post-mortem tissue from patients with Parkinson＇s disease, and also from genetic studies stemming from patients with familial Parkinson＇s disease. Whether triggered by environmental or genetic factors, mitochondrial dysfunction occurs early in the pathogenic process, and is central to Parkinson＇s disease pathology. As such, targeting the mitochondria to slow or halt disease progression is an attractive strategy for disease-modifying agents in Parkinson＇s disease. Indeed, several therapies which target the mitochondria have been investigated as neuroproteetive treatments for Parkinson＇s disease. This review will discuss the evidence supporting mitochondrial dysfunction in Parkinson＇s disease pathology as well as treatment strategies that target the mitochondria.

关键词： Parkinson's disease mitochondria oxidative stress lysosome UPS

Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer

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World Journal of Gastrointestinal Oncology 2023年第8期15卷 1349-1365页

作者： Noel e Donlon Maria Davern Andrew Sheppard Fiona O'Connell Brendan Moran Timothy S Nugent Aisling Heeran James J Phelan Anshul Bhardwaj Christine Butler Narayanasamy Ravi Claire L Donohoe Niamh Lynam-Lennon Stephen Maher John V Reynolds joanne Lysaght Cancer Immunology and Immunotherapy Group Department of SurgeryTrinity Translational Medicine Institute and Trinity St James’s Cancer InstituteTrinity College DublinSt James’s HospitalDublin D08Ireland

BACKGROUND There is an intimate crosstalk between cancer formation,dissemination,treatment response and the host immune system,with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer ***,inducing a purposeful synergistic response between conventional therapies and the immune system remains *** release of damage associated molecular patterns(DAMPs)is indicative of immunogenic cell death and propagation of established immune ***,there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma(OAC)or by immune cells *** To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic *** We investigated the levels of immunogenic cell death-associated DAMPs,calreticulin(CRT)and HMGB1 using an OAC isogenic model of *** expression was also assessed directly using ex vivo cancer patient T cells(n=10)and within tumour biopsies(n=9)both pre and post-treatment with clinically relevant chemo(radio)*** Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in *** increased frequencies of T cell DAMP expression in OAC patients were observed following chemo-(radio)therapy,which was significantly higher in tumour tissue compared with peripheral *** with high expression of HMGB1 had a significantly better tumour regression grade(TRG 1-2)compared to low *** In conclusion,OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors,which correlated with tumour regression grade and lymphatic *** also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

关键词： Damage associated molecular patterns HMGB1 Calreticulin Oesophageal adenocarcinoma T cells Radiation

Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma

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World Journal of Gastroenterology 2022年第21期28卷 2302-2319页

作者： Noel e Donlon Maria Davern Fiona O'Connell Andrew Sheppard Aisling Heeran Anshul Bhardwaj Christine Butler Ravi Narayanasamy Claire Donohoe James J Phelan Niamh Lynam-Lennon Margaret R Dunne Stephen Maher Jacintha O'Sullivan John V Reynolds joanne Lysaght Department of Surgery Trinity Translational Medicine InstituteSt James HospitalDublin D08Ireland

BACKGROUND In the contemporary era of cancer immunotherapy,an abundance of clinical and translational studies have reported radiotherapy(RT)and immunotherapies as a viable option for immunomodulation of many cancer subtypes,with many related clinical trials *** locally advanced disease,chemotherapy or chemoradiotherapy followed by surgical excision of the tumour remain the principal treatment strategy in oesophageal adenocarcinoma(OAC),however,the use of the host immune system to improve anti-tumour immunity is rapidly garnering increased support in the curative *** To immunophenotype OAC patients’immune checkpoint(IC)expression with and without radiation and evaluate the effects of checkpoint blockade on cell *** In the contemporary era of cancer immunotherapy,an abundance of studies have demonstrated that combination RT and IC inhibitors(ICIs)are effective in the immunomodulation of many cancer subtypes,with many related clinical trials *** surgical excision and elimination of tumour cells by chemotherapy or chemoradiotherapy remains the gold standard approach in OAC,the propagation of anti-tumour immune responses is rapidly garnering increased support in the curative *** aim of this body of work was to immunophenotype OAC patients’IC expression with and without radiation and to establish the impact of checkpoint blockade on cell *** study was a hybrid combination of in vitro and ex vivo *** of serum immune proteins was performed by enzyme-linked immunosorbent *** cytometry staining was performed to evaluate IC expression for in vitro OAC cell lines and ex vivo OAC *** viability in the presence of radiation with and without IC blockade was assessed by a cell counting kit-8 *** We identified that conventional dosing and hypofractionated approaches resulted in increased IC expression(PD-1,PD-L1,TIM3,TIGIT)in vitro and ex vivo in *** were two distinct subco

关键词： Oesophageal Cancer Radiotherapy Immunotherapy Immunology Surgery Oncology

Verification of the 2019 GloSea5 Seasonal Tropical Cyclone Landfall Forecast for east China

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Journal of Meteorological Research 2020年第5期34卷 917-925页

作者： joanne CAMP Philip e.BeTT Nicola GOLDING Chris D.HeWITT Timothy D.MITCHeLL Adam A.SCAIFe Met Office Hadley Centre Exeter EX 13PBUK University of Southern Queensland Toowoomba QLD 4350Australia College of engineering Mathematics and Physical SciencesUniversity of ExeterDevon EX44QFUK

A prototype climate service was developed and trialled in early 2019 to provide seasonal forecast of the June–July–August(JJA) tropical cyclone(TC) landfall risk for the east China region ahead of the forthcoming typhoon *** forecasts were produced in both March and April 2019 and a final forecast was released to the China Meteorological Administration(CMA) on 1 May 2019. The trial service was produced by using the Met Office Global Seasonal forecast system(GloSea5), and a forecast of the western Pacific subtropical high(WPSH) index was used to infer the TC landfall risk based on a simple linear regression between historical model WPSH indices and observed TC landfalls in east China. The forecast method shows significant skill for forecasting the JJA TC landfall risk in east China with up to three-month lead time, with the greatest skill for predictions initialized in May. The 2019 forecast provided good guidance of the near-average TC activity observed in east China in JJA 2019. Success of the forecast adds confidence to an improved climate service ahead of the 2020 typhoon season.

关键词： seasonal forecasting typhoons tropical cyclones(TCs) landfall risk east China western Pacific subtropical high(WPSH)