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Role of lysosomal trafficking regulator in autophagic lysosome reformation in neurons:a disease perspective

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Neural Regeneration Research 2024年第5期19卷 957-958页

作者： Prashant Sharma Jenny Serra-vinardell Wendy J.Introne May christine v.Malicdan NIH Undiagnosed Diseases Program Common FundOffice of the DirectorNational Institutes of HealthBethesdaMDUSA Human Biochemical Genetics Section Medical Genetics BranchNational Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA(Serra-Vinardell JIntrone)

Lysosomes are discrete organelles that act as recycling centers for extracellular and intracellular materials,playing a pivotal role in maintaining cellular *** acidic environment,maintained by numerous hydrolytic enzymes,facilitates substrate *** in lysosomal processes can lead to abnormal substrate degradation,significantly impacting cellular *** energy-demanding cells,such as post-mitotic neurons,are especially vulnerable to these changes,often resulting in neurological ***,a conserved catabolic process,requires extensive lysosomal *** plays a key role in removing unnecessary intracellular components,ensuring cellular homeostasis,and promoting cell survival during stress conditions such as starvation,infection,or cellular damage.

关键词： homeostasis lysosomal removing

Timescales of interface-coupled dissolution-precipitation reactions oncarbonates

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Geoscience Frontiers 2019年第1期10卷 17-27页

作者： Francois Renard Anja Royne christine v.Putnis The Njord Centre Physics of Geological Processes Departments of Geoscience and Physics University of Oslo Univ. Grenoble Alpes Univ. Savoie Mont Blanc CNRS Institut für Mineralogie University of Münster The Institute for Geoscience Research (TIGeR) Department of Chemistry Curtin University

In the Earth's upper crust, where aqueous fluids can circulate freely, most mineral transformations are controlled by the coupling between the dissolution of a mineral that releases chemical species into the fluid and precipitation of new minerals that contain some of the released species in their crystal structure, the coupled process being driven by a reduction of the total free-energy of the system. Such coupled dissolution-precipitation processes occur at the fluid-mineral interface where the chemical gradients are highest and heterogeneous nucleation can be promoted, therefore controlling the growth kinetics of the new minerals. Time-lapse nanoscale imaging using Atomic Force Microscopy(AFM) can monitor the whole coupled process under in situ conditions and allow identifying the time scales involved and the controlling parameters. We have performed a series of experiments on carbonate minerals(calcite, siderite, dolomite and magnesite) where dissolution of the carbonate and precipitation of a new mineral was imaged and followed through time. In the presence of various species in the reacting fluid(e. g. antimony, selenium, arsenic, phosphate), the calcium released during calcite dissolution binds with these species to form new minerals that sequester these hazardous species in the form of a stable solid phase. For siderite, the coupling involves the release of Fe^(2+) ions that subsequently become oxidized and then precipitate in the form of FeIIIoxyhydroxides. For dolomite and magnesite,dissolution in the presence of pure water(undersaturated with any possible phase) results in the immediate precipitation of hydrated Mg-carbonate phases. In all these systems, dissolution and precipitation are coupled and occur directly in a boundary layer at the carbonate surface. Scaling arguments demonstrate that the thickness of this boundary layer is controlled by the rate of carbonate dissolution,the equilibrium concentration of the precipitates and the kinetics of diffus

关键词： Carbonates Atomic force microscopy Dissolution Precipitation Boundary layer Replacement

Decreased plasma urotensin Ⅱ levels inversely correlate with extent and severity of coronary artery disease

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Journal of Geriatric Cardiology 2007年第2期4卷 105-110页

作者： v. Borlongan christine E. Stahl Department of Neurology Medical College of Georgia Augusta GA 30912 USA Department of Internal Medicine Dwight D. Eisenhower Army Medical Center Fort Gordon GA 30909 USA

Objective To determine the plasma urolensin Ⅱ(UII) levels in various types of coronary heart disease and to clarify how the plasma UII levels correlate with the clinical presentation, extent and severity of coronary artery atherosclerosis (CAD). Methods: One hundred and three aged patients undergoing elective diagnostic coronary angiography for proven or clinical suspected coronary heart disease were enrolled in this study. The extent and severity of coronary artery disease were evaluated by vessel score and Gensini score, respectively. Plasma UII levels were measured by radioimmunoassay. Results: The plasma UII levels in the patients with modest to severe coronary stenosis (3.03±0.34 pg/ml, 1.83±0.67 pg/ml) were significantly lower than that in subjects with normal coronary artery (4.80±1.11 pg/ml, Pvels in patients with coronary heart disease were also significantly lower than that in patients with insignificant coronary stenosis (P vels in patients with acute coronary syndrome were significantly decreased (1.89±0.51 pg/ml vs 2.42±0.77 pg/ml, P vels were found to be negatively correlated with the severity of coronary artery stenosis (r = -0.488, Pvessel score (r = -0.408, Pverse correlations exist between the plasma UII levels, and the extent and severity of coronary artery stenosis. These findings suggest that plasma UII contribute to the development and progression of coronary artery stenosis, and may be a novel marker to predict clinical types, as well as the extent and severity of coronary artery disease in the patients.

关键词： Urotensin Ⅱ Coronary artery atherosclerosis Coronary heart disease

Influence of psychosocial factors on treatment of elderly Chinese patients with hypertension

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Journal of Geriatric Cardiology 2007年第4期4卷 202-207页

作者： Cesar v. Borlongan christine E. Stahl Department of Neurology Medical College of Georgia Augusta Department of Internal Medicine Dwight D.Eisenhower Army Medical Center Fort Gordon

Objective The aim of the study is to investigate the effects of psychosocial factors on the treatment of elderly patients with hypertension. Methods Atotalof 260 elderly Chinese patients with hypertension were treated with benazepril alone or benazepril combined with amlodipine for 8 weeks. The target blood pressure (BP) (both ved in 180 patients, who were then assigned to the well-controlled BP group;the rest were placed in the modestly controlled BP group. The psychosocial factors present in both groups were assessed by the Hamilton depression scale, Hamilton anxiety scale, life event scale and social support evaluation list before and after anti-hypertensive treatment. Results There were no significant differences in gender, mean age, hist ory of hypertension, education and smoking habit, or in SBP and DBP between the groups before treatment. Significant differences were also not found in all psychosocial factors before and after treatment in the patients. However, significant differences were found between the groups with respect to post-treatment SBP and marital status. The patients with modestly controlled BP had significantly higher scores, as well as incidents, on the depressive, anxiety, and stressful life event scales than those with well-controlled BP. The patients with well-controlled BP had significantly higher scores in tangible support, subjective support, and social support compared to the patients with modestly controlled BP. Logistic regression analysis showed the independent contribution of psychosocial factors in reaching the goal of lowering BP at treatment endpoint in these hypertensive patients. Conclusions The results suggest that psychosocial factors stand as a main barrier to achieving the BP-lowering target in the management of elderly Chinese patients with hypertension.(J Geriatr Cardiol 2007;4:202-207.)

关键词： hypertension psychosocial factor elderly treatment outcome Acknowledgment

New models to study vulvodynia: hyperinnervation and nociceptor sensitization in the female genital tract

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Neural Regeneration Research 2018年第12期13卷 2096-2097页

作者： christine M.Barry Kalyani K.Huilgol Rainer v.Haberberger Anatomy and Histology College of Medicine and Public Health Flinders University Centre for Neuroscience Flinders University

vulvodynia is a prevalent form of chronic pain, most com- monly affecting the vaginal vestibule （vestibulodynia）（Pukall et al., 2016）. Women with vulvodynia describe intense pain in response to light touch of the affected region, such that sexual function and other activities can be severely limited. Medical costs associated with vulvodynia are high, exceeding $21 billion annually in the United States （Xie et al., 2012）. The high level of direct medical costs has been linked to high treatment failure rates. Many women with the disorder consult multiple practitioners and undergo multiple courses of treatment with limited benefit.

关键词： New models to study vulvodynia hyperinnervation and nociceptor sensitization in the female genital tract CFA

Optimised NSAIDs-loaded Biocompatible Nanoparticles

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Nano-Micro Letters 2010年第4期2卷 247-255页

作者： v.Gaelle ROULLIN Maaite CALLEWAERT Michael MOLINARI Franck DELAvOIE Aurelie SECONDE Marie-christine ANDRY Institut de Chimie Mole culaire de Reims CNRS UMR 6229UFR Pharmacie Reims Laboratoire de Microscopies et d’Etudes des Nanostructures UFR des SciencesUniversitéde Reims Champagne-Ardenne Laboratoire de Microscopie Electronique Analytique INSERM UMRS 92621 rue Clement Ader51685 Reims Cedex 2France

In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation *** parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically *** optimized formulation(mean size:145 nm,surface charge:-13 m v) was employed to encapsulate various amounts of NSAIDs in a simple and scalable *** drug release was characterized in vitro by a complete release for 48 *** results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.

关键词： Drug delivery systems(DDS) Biocompatible Emulsion-solvent diffusion method PLGA Glycofurol Non steroidal anti-inflammatory drugs(NSAIDs)

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

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

The transfer and resulting negative effects of nano-and micro-plastics through the aquatic trophic web—A discreet threat to human health

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Water Biology and Security 2022年第4期1卷 1-8页

作者： Charles v.Neves christine C.Gaylarde Jose Antonio Baptista Neto Khaue S.vieira Bruno Pierri Carolina C.C.Waite Daniela C.Scott Estefan M.da Fonseca Department of Geology and Geophysics/LAGEMAR–Laboratorio de Geologia Marinha Instituto de GeocienciasUniversidade Federal FluminenseAvenida Litoranea S/n24210-340NiteroiRJBrazil Department of Microbiology and Plant Biology Oklahoma University770 Van Vleet OvalNormanOK73019USA

The ubiquitous occurrence of plastic nano-and micro-particle contamination has raised concerns about its potential risks and impacts on the global environment,especially in aquatic *** of aquatic species,from different trophic levels,have been affected by this“new”contaminant,which has been reported mainly in their digestive ***,current knowledge about plastic nano-and micro-particle spread and the potential impact on aquatic biota is growing ***,there is a significant lack of understanding of the trophic spread of microplastic contamination and integration of knowledge derived from laboratory assays with that from field research is *** experiments are unable to deal with differentiating between directly and indirectly ingested plastic *** the other hand,laboratory assays evaluating the influence of plastic microparticles and of their adhered or constitutive toxins on representative species cannot satisfactorily simulate the real *** a result,little is known about the effective transfer of plastic particles through the trophic net and the resulting human health *** present review seeks to gather information that can give a more accurate idea of the current situation and future challenges to be faced in mitigating the environmental and human effects of plastic particle pollution in aquatic,particularly estuarine,ecosystems.

关键词： Trophic transfer Plastic matrix additives Anthropogenic pollution Human health Microplastics