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The emerging role of probiotics in neurodegenerative diseases:new hope for Parkinson’s disease?

Neural Regeneration Research 2021年第4期16卷 628-634页

作者： Vanessa Castelli Michele d’Angelo Massimiliano Quintiliani Elisabetta Benedetti maria grazia cifone Annamaria Cimini Department of Life Health and Environmental SciencesUniversity of L’AquilaItaly SIRE Srl NaplesItaly Sbarro Institute for Cancer Research and Molecular Medicine Department of BiologyTemple UniversityPhiladelphiaPAUSA

Neurodegenerative disease etiology is still unclear,but different contributing factors,such as lifestyle and genetic factors are *** components of the gut could play a key role in the gut-brain axis,which is a bidirectional system between the central nervous system and the enteric nervous *** in the composition of the gut microbiota and its function between healthy people and patients have been reported for a variety of human disorders comprising metabolic,autoimmune,cancer,and,notably,neurodegenerative *** can alter the microbiota composition,affecting the gutbrain axis *** nutraceutical interventions have been devoted to normalizing gut microbiome dysbiosis and to improving biological outcomes in neurological conditions,including the use of *** and clinical investigations discussed in this review strengthen the correlation between intestinal microbiota and brain and the concept that modifying the microbiome composition may improve brain neurochemistry,modulating different *** review will discuss the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy,confirming that gut microbiota modulation influences different pro-survival *** investigations in Parkinson’s disease should consider the role of the gut-brain axis and additional comprehension of the underlying mechanisms is extremely necessary.

关键词： age-related diseases brain dysbiosis gut-brain axis microbiota neurodegeneration nutraceuticals Parkinson’s disease probiotics SLAB51

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Role of nitric oxide in the impairment of circular muscle contractility of distended, uninflamed mid-colon in TNBS-induced acute distal colitis in rats

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World Journal of Gastroenterology 2005年第36期11卷 5677-5684页

作者： Luciano Onori Annalisa Aggio Simona D'Alo' Paola Muzi maria grazia cifone Gabriella Mellillo Rachele Ciccocioppo Gennaro Taddei Giuseppe Frieri Giovanni Latella Department of Internal Medicine and Public Health University of L' Aquila 67100 L'Aquila Italy Department of Experimental Medicine University of L' Aquila 67100 L'AquilaItaly Department of Preclinical Pharmacology Dompě SPA Research Center 67100 L'Aquila Italy

AIM： To evaluate the role of nitric oxide （NO） in the motor disorders of the dilated uninflamed mid-colon （DUMC） from trinitrobenzene sulfonic acid （TNBS）-induced acute distal colitis in rats. METHODS： Colitis was induced in male Sprague-Dawley rats by a single intracolonic administration of TNBS. Control rats received an enema of 0.9% saline. The rats were killed 48 h after TNBS or saline administration. Macroscopic and histologic lesions of the colon were evaluated. Myeloperoxidase （MPO） and nitric oxide synthase （NOS） activity were measured on the colonic tissue. In TNBS rats, we evaluated spontaneous and evoked contractile activity in circular muscle strips derived from DUMC in comparison to the same colonic segment of control rats, both in the presence and in the absence of a non-selective NOS isoforms inhibitor N-nitro-L- arginine （L-NNA）. Pharmacological characterization of electric field stimulation （EFS）-evoked contractile responses was also performed. RESULTS： In TNBS rats, the distal colon showed severe histological lesions and a high MPO activity, while the DUMC exhibited normal histology and MPO activity. Constitutive NOS activity was similar in TNBS and control rats, whereas inducible NOS activity was significantly increased only in the injured distal colon of TNBS rats. Isometrically recorded mechanical activity of circular muscle strips from DUMC of TNBS rats showed a marked reduction of the force and frequency of spontaneous contractions compared to controls, as well as of the contractile responses to a contracting stimulus. In the presence of L-NNA, the contractile activity and responses displayed a significantly greater enhancement compared to controls. The pharmacological characterization of EFS contractile responses showed that a cooperative-like interaction between cholinergic muscarinic and tachyldnergic neurokinin 1 and 2 receptors mediated transmission in DUMC of TNBS rats vs a simple additive interaction in controls. CONCLUSION： The results

关键词： TNBS colitis Colonic dilatation Colonic motility Nitric oxide synthase

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Ex vivo models of retinal neurovascular diseases

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Annals of Eye Science 2022年第2期7卷 1-7页

作者： maria grazia Rossino Department of Biology University of PisaPisaItaly

Background:The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy(DR).It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo *** particular,it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR ***:Ex vivo retinal fragments derived from 3-to 5-week-old C57BL/6J *** particular,after dissection,the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells *** in culture,the explants could be treated in stress conditions typical of *** particular,this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose(HG),advanced glycation end product(AGE),and oxidative stress(OS).In the end,this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective ***:The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as ***,they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo *** conclusion,retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.

关键词： Retinal explants diabetic retinopathy(DR) neurovascular diseases

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Specific contribution of mannose-binding lectin murine isoforms to brain ischemia/reperfusion injury

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Cellular & Molecular Immunology 2020年第3期17卷 218-226页

作者： Laura Neglia Marco Oggioni Domenico Mercurio maria-grazia De Simoni Stefano Fumagalli1 Istituto di Ricerche Farmacologiche Mario Negri IRCCS Department of NeuroscienceMilanItaly

Mannose-binding lectin(MBL),an initiator of the lectin pathway(LP)of complement activation,is detrimental in ischemic stroke,as shown in clinical studies and rodent *** humans have one functional MBL protein,rodents have two isoforms,MBL-A and MBL-C,whose functions relative to that of human MBL are *** permit the clinical translation of preclinical data,we aimed to define the specific contributions of MBL-A and MBL-C to brain *** subjected mice with double(MBL^(−/−))or single(MBL-A^(−/−)or MBL-C^(−/−))MBL isoform depletion to transient middle cerebral artery occlusion(tMCAo).MBL^(−/−) mice had fewer neurological deficits and smaller ischemic lesions than WT ***-A^(−/−) mice had smaller lesions than WT mice and exhibited no significant behavioral defects,whereas MBL-C^(−/−) mice did not differ from WT *** induction of Mbl1 and Mbl2(the MBL-A and MBL-C genes)expression 48 h after tMCAo was similar across *** time course of Mbl1 and Mbl2 expression in WT ischemic mice showed that Mbl1 activation occurred earlier(24 h)than Mbl2 activation(48 h).The plasma levels of MBL-A and MBL-C in MBL-C^(−/−) and MBL-A^(−/−) mice,respectively,were similar to those in WT mice both at baseline and at 48 h after *** 48 h,MBL-A^(−/−)ischemic mice showed higher MBL-C levels in the brain than WT *** and MBL-C^(−/−) ischemic mice had higher LP activity in plasma and,accordingly,higher levels of C3 deposition in the brain than MBL-A^(−/−) and MBL^(−/−) *** conclusion,mice with depletion of both MBL isoforms exhibited strong protection from ischemia/reperfusion ***-A was the main contributor to injury,likely owing to its earlier activation after ischemia and more efficient activation of the complement system than MBL-C.

关键词： injury depletion likely

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Emerging actionable targets to treat therapyresistant colorectal cancers

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Cancer Drug Resistance 2022年第1期5卷 36-63页

作者： Emanuela Grassilli maria grazia Cerrito Department of Medicine and Surgery University of Milano-BicoccaMonza 20900Italy

In the last two decades major improvements have been reached in the early diagnosis of colorectal cancer(CRC)and,besides chemotherapy,an ampler choice of therapeutic approaches is now available,including targeted and *** that,CRC remains a“big killer”mainly due to the development of resistance to therapies,especially when the disease is diagnosed after it is already *** the same time,our knowledge of the mechanisms underlying resistance has been rapidly expanding which allows the development of novel therapeutic options in order to overcome *** far as resistance to chemotherapy is concerned,several contributors have been identified such as:intake/efflux systems upregulation;alterations in the DNA damage response,due to defect in the DNA checkpoint and repair systems;dysregulation of the expression of apoptotic/anti-apoptotic members of the BCL2 family;overexpression of oncogenic kinases;the presence of cancer stem cells;and the composition of the tumoral microenvironment and that of the gut ***,several mechanisms are also involved in the resistance to targeted and/or *** example,overexpression and/or hyperactivation and/or amplification of oncogenic kinases can sustain resistance to targeted therapy whereas the composition of the gut microbiota,as well as that of the tumoral niche,and defects in DNA repair systems are crucial for determining the response to *** this review we will make an overview of the main resistance mechanisms identified so far and of the new therapeutic approaches to overcome it.

关键词： Colorectal cancer resistance chemotherapy target therapy EGFR ERBB2 MET BRAF kinase inhibitors immune checkpoint inhibitors gut microbiota

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Thermal Radiation Modelling in Tunnel Fires

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Advances in Applied Mathematics and Mechanics 2011年第3期3卷 327-353页

作者： Paolo Ciambelli maria grazia Meo Paola Russo Salvatore Vaccaro Department of Industrial Engineering University of Salernovia Ponte don Melillo 84084 Fisciano(SA)Italy

Modelling based on Computational Fluid Dynamics(CFD)is by now effectively used in fire research and hazard *** on the scenario,radiative heat transfer can play a very important role in enclosure combustion events such as tunnel *** this work,the importance of radiation and the effect of the use of different approaches to account for it were ***,small-scale tunnel fire simulations were performed and the results compared with experimental data,then realistic full-scale scenarios were *** results show up the capability of CFD modelling to reproduce with good approximation tunnel *** proved to be noteworthy mainly when the scale of the fire is relatively *** the various approaches employed to simulate radiation,the use of the Discrete Transfer model gave the most accurate results,mainly when the absorption-emission characteristics of the combustion products were taken into ***,the suitability of the use of CFD in quantitative Fire Hazard Analysis is discussed.

关键词： CFD radiation modelling fire hazard analysis tunnel fires

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Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

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World Journal of Gastroenterology 2016年第36期22卷 8078-8093页

作者： maria grazia Clemente Claudia Mandato Marco Poeta Pietro Vajro Pediatric Clinic Department of SurgicalMicrosurgical and Medical SciencesUniversity of Sassari07100 SassariItaly Pediatrics of AORN Santobono-Pausilipon 80123 NaplesItaly Pediatrics Department of MedicineSurgery and Dentistry'Scuola Medica Salernitana'University of Salerno84081 BaronissiItaly ELFID European Laboratory for the Investigation of Food Induced Disease 80138 NaplesItaly

Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance(IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis(NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data(BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR(acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy(the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of *** pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes

关键词： Non-alcoholic fatty liver disease Childhood obesity Non-alcoholic steatohepatitis Hepatic metabolic syndrome Non-alcoholic fatty liver disease diagnosis

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Modelling the dynamics of exchanged novel coronavirus(2019-nCov)between regions in terms of time and space

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Infectious Disease Modelling 2020年第1期5卷 714-719页

作者： Massimo Fioranelli maria grazia Roccia A.Beesham Istituto Terapie Sistemiche Integrate Via Flaminia 44900181RomeItaly Faculty of Natural Sciences Mangosuthu University of TechnologyP O Box 12363Umlazi4026South Africa

To date,many models have been proposed which estimate the transmission risk of COVID-19 in terms of time;however,its dependency on space dimensions has been *** this research,by multiplying risk parameters in certain regions and bridging,we obtain a stable action,which means that the transmission risk worldwide could shrink to a ***,by increasing the risk parameters in one region,the risk parameters in other regions ***,by adding space dimensions to the parameters in transmission risk models,and using the wave equations of manifolds for the regions,we obtain the dynamics of the exchanged novel coronavirus(2019-nCov)between *** calculate the risk factors of COVID19 for different regions in this model,and observe that they are in good agreement with experimental data.

关键词： COVID19 Transmission risk Time Region Space

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Overview of current detection methods and microRNA potential in Clostridioides difficile infection screening

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World Journal of Gastroenterology 2023年第22期29卷 3385-3399页

作者： Marco Bocchetti maria grazia Ferraro Federica Melisi Piera Grisolia marianna Scrima Alessia maria Cossu Tung On Yau Department of Precision Medicine University of Campania“Luigi Vanvitelli”Naples 80138Italy Department of Molecular Oncology Precision Medicine Laboratory and COVID19 LaboratoryBiogem ScarlAriano Irpino 83031Italy School of Infection and Immunity College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgow G128QQUnited Kingdom Department of Pharmacy School of Medicine and SurgeryUniversity of Naples“Federico Ⅱ”Naples 80131Italy School of Science and Technology Nottingham Trent UniversityNottingham NG118NSUnited Kingdom Department of Rural Land Use Scotland’s Rural CollegeAberdeen AB219YAScotlandUnited Kingdom Department of Health Science University of the PeoplePasadenaCA 9110112United States

Clostridioides difficile(formerly called Clostridium difficile,***)infection(CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and *** detection and appropriate disease management appear to be ***,although the majority of cases are hospital-acquired CDI,community-acquired CDI cases are also on the rise,and this vulnerability is not limited to immunocompromised *** treatments and/or gastrointestinal tract surgeries may be required for patients diagnosed with digestive *** treatments could suppress or interfere with the patient’s immune system and disrupt gut flora homeostasis,creating a suitable microecosystem for *** ***,stool-based non-invasive screening is the first-line approach to CDI diagnosis,but the accuracy is varied due to different clinical microbiology detection methods;therefore,improving reliability is clearly *** this review,we briefly summarised the life cycle and toxicity of ***,and we examined existing diagnostic approaches with an emphasis on novel biomarkers such as *** biomarkers can be easily detected through noninvasive liquid biopsy and can yield crucial information about ongoing pathological phenomena,particularly in CDI.

关键词： Clostridioides difficile microRNA Diagnostic Prognostic Biomarker

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Biobased Vanillic Acid and Ricinoleic Acid: Building Blocks for Fully Renewable Copolyesters

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Journal of Renewable Materials 2018年第1期6卷 126-135页

作者： Claudio Gioia maria Barbara Banella grazia Totaro Micaela Vannini Paola Marchese Martino Colonna Laura Sisti Annamaria Celli University of Bologna Department of CivilChemicalEnvironmental and Materials EngineeringVia Terracini 28Bologna40131Italy

New fully biobased polyether/esters have been synthesized by a one-pot polymerization reaction of ricinoleic acid(RA),vanillic acid(VA)and ethylene carbonate(EC).In particular,EC selectively reacts with the phenolic group of VA to obtain in-situ 4-(2-hydroxyethoxy)-3-methoxybenzoate(EV),suitable for subsequent copolymerization with *** procedure was carried out in a single step,without any *** structure and thermal properties of the new materials were studied in order to explore relationships between composition and final *** combination of EV,bearing a rigid aromatic structure,with RA,characterized by high flexibility and potential biocidal activity,allows the production of a novel class of fully biobased aliphatic-aromatic polymers presenting tuneable thermal properties and suitable for a range of applications,for example,in active packaging and biomedical fields.

关键词： Biobased building blocks vanillic acid ricinoleic acid copolyesters

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