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*** implants for corneal regeneration in patients at high risk of rejecting donor transplantation

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Annals of Eye Science 2019年第1期 197-197页

作者： May Griffith M.Mirazul Islam Oleksiy Buznyk Fiona Simpson Per Fagerholm Keith Meek Virender Sangwan Department of Ophthalmology and Institute of Biomedical Engineering University of Montreal and Maisonneuve-Rosemont Hospital and CHUM Research CentresMontrealQCCanada Department of Clinical and Experimental Medicine Linköping UniversityLinköpingSweden Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary Harvard Medical SchoolBostonMAUSA Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine OdessaUkraine School of Optometry and Vision Sciences College of Biomedical and Life Sciences and Cardiff Institute for Tissue Engineering and Repair(CITER)Cardiff UniversityCardiffUK Tej Kohli Cornea Institute LV Prasad Eye InstituteHyderabadIndia Dr.Schroff charity Eye hospital New DehliIndia

Background:Patients with inflammation or severe corneal pathology are often at high risk of rejecting the human donor corneas that they receive during *** goal was to determine whether cell-free implants incorporating phosphorylcholine-based polymer,2-methacryloyloxyethyl phosphorylcholine(MPC),which has inflammation suppressing properties,can support repair and regeneration of ulcerated,high-risk ***:Interpenetrating networks of recombinant human collagen and MPC(RHC-MPC)were fabricated into corneal implants in a certified and monitored *** open-label,first-in-human observational study was conducted following ISO 14971 and 14155:2011,the Declaration of Helsinki and relevant laws of Ukraine and India,after respective ethical approval and trial *** unilaterally blind patients,aged 36 to 76 years old,diagnosed with conditions putting them at high risk of rejecting conventional corneal transplantation,and capable of providing informed written consent were grafted and followed up for an average of two ***,RHC like native collagen is a large macromolecule and difficult to process and is ***,small,customisable analogs to collagen comprising collagen-like peptides(CLP)conjugated to polyethylene glycol(PEG)were *** CLP-PEG analogs like RHC were combined with MPC into implants and tested in mini-pig models with alkali burned corneas,a high-risk ***:One patient had an unrelated infection that necessitated re-grafting and was excluded from the *** RHC-MPC implants in the remaining six patients were stably integrated throughout the entire observational *** was regeneration of the cornea epithelium and *** vision improvement was observed in in patients with damaged corneas due to *** two weeks post-operation,RHC-MPC implanted corneas of patients with active ulcers were free from the symptoms of pain,irritation and *** the

关键词： Cornea inflammation implant clinical trial pigs

T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： Michelle R Goulart Konstantinos Stasinos Rachel Elizabeth Ann Fincham Francesca R Delvecchio Hemant M Kocher Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival *** has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T *** cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant *** tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted ***,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion Tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma

The interplay between inflammation,immunity and commensal microflora in glaucomatous neurodegeneration

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Annals of Eye Science 2019年第1期4卷 37-40页

作者： Christin Henein Peng T.Khaw National Institute for Health Research Biomedical Research Centre for Ophthalmology Moorfields Eye Hospital and UCL Institute of OphthalmologyLondonUK School of Pharmacy University College LondonLondonUK

The immensely diverse and rich human gut microbiome has a huge potential to impact health and disease(1).Gut microbiome dysbiosis has been associated with gastro-intestinal inflammatory conditions and extra-intestinal disorders;such as stroke,depression,neurodegenerative,cardiovascular and metabolic disorders(2-6).In the September 2018 issue of nature communications,Chen and colleagues report the findings from a study that found commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma,in mouse glaucoma models(7).

关键词： glaucoma immunity inflammation

Alcoholic liver disease:Utility of animal models

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World Journal of Gastroenterology 2018年第45期24卷 5063-5075页

作者： Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for Bioengineering(IBioE) School of EngineeringFaraday BuildingThe University of EdinburghEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Human Anatomy and Embryology Complutense University School of MedicineMadrid 28040Spain Instituto de Neurociencias Consejo Superior de Investigaciones CientíficasUniversidad Miguel HernándezSan Juan de Alicante 03550Spain Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain Department of Genetics Physiology and MicrobiologyFaculty of BiologyUniversidad ComplutenseMadrid 28040Spain Department of Internal Medicine Ⅲ University Hospital RWTH AachenAachen 52062Germany

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

关键词： Steatohepatitis Cirrhosis Hepatocellular carcinoma Alcoholic liver disease Reactive oxygen species

Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

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World Journal of Gastroenterology 2016年第30期22卷 6757-6763页

作者： Nidhi Midhu Sagar Michael McFarlane Chuka Nwokolo Karna Dev Bardhan Ramesh Pulendran Arasaradnam School of Medicine University of Warwick Coventry CV4 7AL United Kingdom Department of Gastroenterology University Hospitals Coventry and Warwickshire Coventry CV2 2DX United Kingdom Department of Gastroenterology Rotherham General Hospital NHS Trust Rotherham S60 2UD United Kingdom Clinical Sciences Research Institute University of Warwick Coventry CV2 2DX United Kingdom

Bile acids(BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor(FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins(VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-Ⅱ, very low-density lipoproteins receptor(VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-Ⅲ, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea(BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

关键词： Bile acids Bile acid diarrhea Triglycerides Farnesoid X receptor

Association between Active School Travel and Depressive Symptoms among 51,702 Adolescents in 26 Low- and Middle-Income Countries

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International Journal of Mental Health Promotion 2021年第2期23卷 141-153页

作者： Shuan Liu Sitong Chen Xiaohong Zhu Brendon Stubbs Qian Yu Mark D.Griffiths Can Jiao Aiguo Chen Md Mahbub Hossain Zsolt Demetrovics Albert S.Yeung Jinming Li Xingyu Zhang Liye Zou Faculty of Educational Science South China Normal UniversityGuangzhou510631China Institute for Health and Sport Victoria UniversityMelbourne8001Australia College of Sports Science Jishou UniversityJishou212013China Department of Psychological Medicine Institute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonWC2R 2LSUK Exercise and Mental Health Laboratory Institute of KEEP Collaborative InnovationShenzhen UniversityShenzhen518060China Psychology Department Nottingham Trent UniversityNottinghamNG14FQUK School of Psychology Shenzhen UniversityShenzhen518060China College of Physical Education Yangzhou UniversityYangzhou225127China Department of Health Promotion and Community Health Sciences School of Public HealthTexas A&M UniversityCollege StationTX77843USA Institute of Psychology ELTE Eötvös Loránd UniversityBudapest1064Hungary Centre of Excellence in Responsible Gaming University of GibraltarEuropa PointGX111AAGibraltar Depression Clinical and Research Program Massachusetts General HospitalBostonMA 02114USA

Little is known about the role of active school travel(AST)on mental health among ***,this study aimed to explore the AST-depression association among adolescents aged 12–15 years from 26 low-and middle-income countries(LMICs).Data from the Global School-based Student Health Survey were analyzed in 51,702 adolescents[mean(SD)age 13.8(1.0)years;49.3%boys).Both depressive symptoms and AST were assessed by a single question self-reported measure,*** who reported having 5 days or above were considered as *** logistic regression analysis(accounting for sampling weights)was performed while controlling for gender,age,physical activity,sedentary behavior,and food insecurity,and a countrywide meta-analysis was *** prevalence of depressive symptoms and AST were 30.1%and 37.0%,*** with those not having AST,adolescents with AST were less likely to have self-reported depressive symptoms(OR=0.88,95%CI:0.85-0.93)regardless of *** meta-analysis demonstrated that having AST versus not having AST was associated with 12%lower odds for depressive symptoms(OR=0.88;95%CI:0.82-0.94)but with a moderate between-country heterogeneity(I^(2)=59.0%).Based on large samples of adolescents from LMICs,it would be expected that AST may play a critical role in preventing adolescent depression ***,it is necessary to consider more country-specific factors when implementing AST-related mental health *** studies should adopt the solid study design to confirm or negate our researchfindings.

关键词： Active travel depression Global School-based Health Survey low-and middle-income countries