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Integrin-targeting with peptide-bioconjugated semiconductor-magnetic nanocrystalline heterostructures

Nano Research 2016年第3期9卷 644-662页

作者： Gianpiero Valente Nicoletta Depalo Ivan de Paola Rosa Maria lacobazzi Nunzio Denora Valentino Laquintana Roberto Comparelli Emiliano Altamura Tiziana Latronico michele Altomare Elisabetta Fanizza Marinella Striccoli Angela Agostiano michele saviano Annarita Del Gatto Laura Zaccaro Maria Lucia Curri Universita degli Studi di Bari Aldo Moro Dipartimento di Chimica Via Orabona 4 70125 - Bari Italy Istituto per i Processi Chimico-Fisici-CNR UOS Bari Via Orabona 4 70125 - Bari Italy Istituto di Biostrutture e Bioimmagini-CNR Via Mezzocannone 16 80134 - Napoli Italy Universita degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via Orabona 4 70125 - Bari Italy Universita degli Studi di BariAIdo Moro Dipartimento di Bioscienze Biotecnologie e Biofarmaceutica Via Orabona 4 70125 - Bari Italy lstituto di Cristallografia-CNR Via Amendola 122/0 70126 Bari Italy

Binary asymmetric nanocrystals （BNCs）, composed of a photoactive TiO2 nanorod joined with a superparamagnetic γ-Fe203 spherical domain, were embedded in polyethylene glycol modified phospholipid micelle and successfully bioconjugated to a suitably designed peptide containing an RGD motif. BNCs represent a relevant multifunctional nanomaterial, owing to the coexistence of two distinct domains in one particle, characterized by high photoactivity and magnetic properties, that is particularly suited for use as a phototherapy and hyperthermia agent as well as a magnetic probe in biological imaging. We selected the RGD motif in order to target integrin expressed on activated endothelial cells and several types of cancer cells. The prepared RGD-peptide/BNC conjugates, comprehensively monitored by using complementary optical and structural techniques, demon- strated a high stability and uniform dispersibility in biological media. The cytotoxicity of the RGD-peptide/BNC conjugates was studied in vitro. The cellular uptake of RGD-peptide conjugates in the cells, assessed by means of two distinct approaches, namely confocal microscopy analysis and emission spectroscopy determination in cell lysates, displayed selectivity of the RGD-peptide-BNC conjugate for the cw]33 integrin. These RGD-peptide-BNC conjugates have a high potential for theranostic treatment of cancer.

关键词： nanocrystallineheterostructures,photoactive semiconductor,magnetic nanostructure,cyclic RGD peptide,αvβ3 integrin,active targeting

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Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

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World Journal of Gastroenterology 2024年第18期30卷 2391-2396页

作者： michele Barone Section of Gastroenterology Department of Precision and Regenerative Medicine-Jonian Area-University of BariBari 70124Italy

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology.The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis.Here,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human studies.Angiotensin-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of HCC.Finally,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.In this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this pathway.However,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

关键词： Renin-angiotensin system Liver fibrosis Hepatic stellate cells Autophagy Hepatocellular carcinoma

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Metabolomic evidence of independent biotransformation pathways for terpenes in two specialist mammalian herbivores (genus Neotoma)

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Integrative Zoology 2024年第1期19卷 143-155页

作者： Katharina SCHRAMM michele SKOPEC Denise DEARING Department of Biology University of UtahSalt Lake CityUtahUSA Department of Zoology Weber State UniversityOgdenUtahUSA

Herbivory is common in mammals,yet our understanding of detoxification processes used by mammals to biotrans-form plant secondary compounds(PSCs)is limited.Specialist herbivores are thought to have evolved detoxifica-tion mechanisms that rely more heavily on energetically cheap Phase I biotransformation reactions to process high levels of PSCs in their diets.We explored this hypothesis by comparing the urinary metabolite patterns of two spe-cialist herbivores(genus Neotoma).Neotoma stephensi is an obligate specialist on one-seeded juniper(Juniperus monosperma).Neotoma lepida is a generalist forager across its range,yet populations in the Great Basin specialize on Utah juniper(J.osteosperma).While both juniper species have high levels of terpenes,the terpene profiles and quantities differ between the two.Individuals from both woodrat species were fed diets of each juniper in a cross-over design.Urine,collected over a 24-h period,was extracted and analyzed in an untargeted metabolomics approach using both GC-MS and HPLC-MS/MS.The obligate specialist N.stephensi excreted a unique pattern of Phase I metabolites when fed its native juniper,while N.lepida excreted a unique pattern of Phase II metabolites when fed its native juniper.Both woodrat species utilized the Phase II metabolic pathway of glucuronidation more heavily when consuming the more chemically diverse J.osteosperma,and N.stephensi utilized less glucuronida-tion than N.lepida when consuming J.monosperma.These results are consistent with the hypothesis that obligate specialists may have evolved unique and efficient biotransformation mechanisms for dealing with PSCs in their diet.

关键词： dietary specialization herbivory juniper metabolomics Neotoma

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Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

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World Journal of Gastroenterology 2024年第25期30卷 3147-3151页

作者： michele Barone Section of Gastroenterology Department of Precision and Regenerative Medicine-Jonian Area-University of BariBari 70124Italy

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

关键词： Hematological malignancy Hepatitis Hepatitis B virus-DNA Bruton’s tyrosine kinase Previously resolved hepatitis B virus infection

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Colon and rectal cancer:An emergent public health problem

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World Journal of Gastroenterology 2024年第7期30卷 644-651页

作者： Marina Pinheiro David Nascimento Moreira michele Ghidini LAQV REQUIMTEDepartment of ChemistryFaculty of PharmacyUniversity of Porto4050-313 PortoPortugal Unidade de Saúde Pública Unidade Local de Saúde Barcelos/EsposendeBarcelinhos 4755-069BragaPortugal Medical Oncology Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy

Colorectal cancer ranks third globally,with a high mortality rate.In the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of age.These screenings have allowed an early diagnosis and consequently an improvement in health indicators.Colon and rectal cancer(CRC)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and mortality.This study is a review of CRC pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of CRC.Finally,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

关键词： Colon and rectal neoplasia Colon and rectal tumor Mortality Morbidity

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Therapeutic advances in neural regeneration for Huntington’s disease

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Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini michele d’Angelo Department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, num

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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Close relationship between mediators of inflammation and pancreatic cancer:Our experience

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World Journal of Gastroenterology 2024年第23期30卷 2927-2930页

作者： Francesca Vescio michele Ammendola Giuseppe Currò Silvia Curcio Department General Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy Science of Health Department Digestive Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy

In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.

关键词： Mast cells C-Kit receptor Tryptase Angiogenesis Microvascular density Endothelial area Pancreatic tumor tissue Adjacent normal tissue

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Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions:theoretical basis

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 951-962页

作者： Ciro Caruso Luca D’Andrea Mario Troisi michele Rinaldi Raffaele Piscopo Salvatore Troisi Ciro Costagliola Corneal Transplant Center Pellegrini HospitalVia Portamedina alla Pignasecca 41Napoli 80127Italy Eye Clinic Department of NeurosciencesReproductive and Odontostomatological SciencesUniversity of Naples Federico IINaples 80131Italy Public Health Department University of Naples Federico IINaples 80131Italy Salerno Hospital University Ophthalmologic UnitBaronissiCampania 84131Italy

Keratoconus is an ectatic condition characterized by gradual corneal thinning,corneal protrusion,progressive irregular astigmatism,corneal fibrosis,and visual impairment.The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages,gas-permeable rigid contact lenses,scleral lenses,implantation of intrastromal corneal ring or corneal transplants for most advanced stages.In keratoconus cases showing disease progression corneal collagen crosslinking(CXL)has been proven to be an effective,minimally invasive and safe procedure.CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation,resulting in stromal crosslinks formation.The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models,from the original Dresden protocol to the most recent developments in the technique,reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols.Finally,the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

关键词： corneal collagen cross linking keratoconus custom fast protocol Dresden protocol lambert-beer law Bunsen-roscoe law

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Potential of GSHP coupled with PV systems for retrofitting urban areas in different European climates based on archetypes definition

Energy and Built Environment

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Energy and Built Environment 2024年第3期5卷 374-392页

作者： Laura Carnieletto Antonino Di Bella Davide Quaggiotto Giuseppe Emmi Adriana Bernardi michele De Carli Department of Industrial Engineering–DII University of Padovavia Venezia 1PadovaItaly University of Ferrara Italy CNR–National Research Council PadovaItaly

According to the recent policies regarding energy use in buildings and the need of retrofit strategies,the aim of this work is to support policies concerning the installation of ground source heat exchangers in urban and historical areas,raising the awareness on the potential energy saving achievable with optimal sizing and limited impact on the urban environment.Archetypes have been developed distinguishing among existing and historic buildings,focusing on single-family terrace houses,which are the typical residential buildings in European historic centres.A methodology for the optimal sizing of ground source heat pumps,eventually considering dual-source system or air system has been developed combining simulations of a photovoltaic system to estimate the self-sufficiency and the self-consumption for five orientations of the building.Extreme results have been obtained for warm cli-mates,with negligible heating energy demand and possibly free cooling systems rather than traditional cooling systems needed in wintertime.Penalty temperature was acceptable despite unbalanced energy demands.With proper inclination,photovoltaic systems could provide up to 40%of self-sufficiency share also in northern cli-mates.An energy-economic analysis was carried out obtaining a variety of cases representing a general overview of the European building stock and the potential benefits achievable in terms of renewable energy share,energy savings and economic investments needed to be extended to simulations at urban scale.

关键词： Energy use database Ground source heat exchangers Urban context Energy retrofit Integrated renewables

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Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

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World Journal of Gastroenterology 2024年第15期30卷 2081-2086页

作者： michele Nardolillo Fabiola Rescigno Mario Bartiromo Dario Piatto Stefano Guarino Pierluigi Marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

关键词： Metabolic(dysfunction)associated fatty liver disease Renal Function Children Obesity

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