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Neural Regeneration Research 2025年第6期20卷 1703-1704页

作者： Paolo Abondio Francesco Bruno irccs istituto delle Scienze Neurologiche di Bologna BolognaItaly Association for Neurogenetic Research(ARN) Lamezia TermeCatanzaroItaly

The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural *** traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain *** the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.

关键词： function artificial landscape

Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous *** copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple *** review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper ***,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

Assessing the response of human primary macrophages to defined fibrous architectures fabricated by melt electrowriting

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Bioactive Materials 2023年第3期21卷 209-222页

作者： Carlotta Mondadori Amit Chandrakar Silvia Lopa Paul Wieringa Giuseppe Tal`o Silvia Perego Giovanni Lombardi Alessandra Colombini Matteo Moretti Lorenzo Moroni irccs istituto ortopedico galeazzi Cell and Tissue Engineering LaboratoryMilanItaly Complex Tissue Regeneration Department MERLN Institute for Technology-Inspired Regenerative MedicineMaastrichtthe Netherlands irccs istituto ortopedico galeazzi Laboratory of Experimental Biochemistry and Molecular BiologyMilanItaly Department of Athletics Strength and ConditioningPozna´n University of Physical EducationPozna´nPoland irccs istituto ortopedico galeazzi Orthopaedic Biotechnology LabMilanItaly Regenerative Medicine Technologies Lab Ente Ospedaliero CantonaleBellinzonaSwitzerland Service of Orthopaedics and Traumatology Department of SurgeryEnte Ospedaliero CantonaleLuganoSwitzerland Euler Institute Faculty of Biomedical SciencesUniversit`a della Svizzera ItalianaLuganoSwitzerland

The dual role of macrophages in the healing process depends on macrophage ability to polarize into phenotypes that can propagate inflammation or exert anti-inflammatory and tissue-remodeling *** scaf-fold geometry has been proposed as a strategy to influence macrophage behavior and favor the positive host response to ***,we fabricated Polycaprolactone(PCL)scaffolds by Melt Electrowriting(MEW)to investigate the ability of scaffold architecture to modulate macrophage *** human macrophages unpolarized(M0)or polarized into M1,M2a,and M2c phenotypes were cultured on PCL films and MEW scaffolds with pore geometries(square,triangle,and rhombus grid)characterized by different angles.M0,M2a,and M2c macrophages wrapped along the fibers,while M1 macrophages formed clusters with rounded *** bridges were formed only for angles up to 90◦.No relevant differences were found among PCL films and 3D scaffolds in terms of surface ***206 and CD163 were highly expressed by M2a and M2c macrophages,with M2a macrophages presenting also high levels of CD86.M1 macrophages expressed moderate levels of all *** rhombus architecture promoted an increased release by M2a macrophages of IL10,IL13,and sCD163 compared to PCL *** proangiogenic factor IL18 was also upregulated by the rhombus configuration in M0 and M2a macrophages compared to PCL *** interesting findings obtained for the rhombus architecture represent a starting point for the design of scaffolds able to modulate macrophage phenotype,prompting investigations addressed to verify their ability to facilitate the healing process in vivo.

关键词： Macrophage Melt electrowriting Additive manufacturing Scaffold design Scaffold geometry

Primary malignant tumors of bone surface:a review with emphasis in differential diagnosis

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 632-646页

作者： Marina Pacheco Alberto Righi Department of Pathology IRCCS Istituto Ortopedico RizzoliBologna 40136Italy

Surface tumors of the bone are broadly defined as a diverse group of osteogenic and chondrogenic benign and malignant neoplasms that arise adjacent to the outer surface of cortical *** may be a cause of diagnostic difficulty due to a degree of histological overlap,rarity,and *** this review we summarize the different histological types of primary malignant tumors of bone surface,namely,secondary peripheral chondrosarcoma,periosteal chondrosarcoma,parosteal osteosarcoma,dedifferentiated parosteal osteosarcoma,periosteal osteosarcoma,and high-grade surface *** provide a comprehensive updated review of their pathogenesis and highlight radiological,macroscopic,and histopathological features and recently available ancillary diagnostic tools that may aid in the differential diagnosis.

关键词： Secondary peripheral chondrosarcoma periosteal chondrosarcoma parosteal osteosarcoma periosteal osteosarcoma high-grade surface osteosarcoma

Preoperative and postoperative risk factors for periprosthetic joint infection in primary total hip arthroplasty:A 1-year experience

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World Journal of Orthopedics 2022年第10期13卷 903-910页

作者： Giuseppe Ferdinando Tella Cesare Donadono Francesco Castagnini Barbara Bordini Monica Cosentino Michele Di Liddo Francesco Traina Ortopedia-Traumatologia e Chirurgia protesica e dei reimpianti d'anca e di ginocchio IRCCS Istituto Ortopedico RizzoliBologna 40125Italy Laboratorio di Tecnologia Medica IRCCS Istituto Ortopedico RizzoliBologna 40125Italy

BACKGROUND Periprosthetic joint infection(PJI)in primary total hip replacement(THR)is one of the most important threats in orthopedic surgery,so one important surgeon’s target is to avoid or early diagnose a *** the incidence of PJI is very low(0.69%)in our department,with an average follow-up of 595 d,this infection poses a serious threat due to the difficulties of treatment and the lower functional outcomes after *** To study the incidence of PJI in all operations occurring in the year 2016 in our department to look for predictive signs of potential *** We counted 583 THR for 578 patients and observed only 4 cases of infection(0.69%)with a mean follow-up of 596 d(min 30,max 1451).We reviewed all medical records to collect the data:duration and time of the surgery,presence,type and duration of the antibiotic therapy,preoperative diagnosis,blood values before and after surgery,transfusions,presence of preoperative drugs(in particularly anticoagulants and antiaggregant,corticosteroids and immunosuppressants),presence of some comorbidities(high body mass index,blood hypertension,chronic obstructive pulmonary disease,cardiac ischemia,diabetes,rheumatological conditions,previous local infections).RESULTS No preoperative,intraoperative,or postoperative analysis showed a higher incidence of *** did not find any class with evident major odds of *** our study,we did not find any border value to predict PJI and all patients had similar values in both groups(non-PJI and PJI).Only some categories,such as female patients,showed more frequency of PJI,but this difference related to sex was not statistically *** We did not find any category with a higher risk of PJI in THR,probably due to the lack of few cases of infection.

关键词： Primary total hip replacement Periprosthetic joint infection Preoperative risk factors Postoperative risk factors Preoperative and postoperative blood value Total hip arthroplasty

Metrically measuring liver biopsy:A chronic hepatitis B and C computer-aided morphologic description

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World Journal of Gastroenterology 2008年第48期14卷 7335-7344页

作者： Nicola Dioguardi Fabio Grizzi Barbara Fiamengo Carlo Russo Laboratories of Quantitative Medicine Istituto Clinico Humanitas IRCCS Department of Pathology Istituto Clinico Humanitas IRCCS

AIM： To describe a quantitative analysis method for liver biopsy sections with a machine that we have named ＂Dioguardi Histological Metriser＂ which automatically measures the residual hepatocyte mass （including hepatocytes vacuolization）, inflammation, fibrosis and the loss of liver tissue ***： We analysed digitised images of liver biopsy sections taken from 398 patients, The analysis with Dioguardi Histological Metriser was validated by comparison with semi-quantitative scoring ***： The method provides：（1） the metrical extension in two-dimensions （the plane） of the residual hepatocellular set, including the area of vacuoles pertinent to abnormal lipid accumulation; （2） the geo- metric measure of the inflammation basin, which distinguishes intra-basin space and extra-basin dispersed parenchymal leukoo/tes; （3） the magnitude of collagen islets, （which were considered truncated fractals and classified into three degrees of magnitude）; and （4） the tectonic index that quantifies alterations （disorders） in the organization of liver tissue. Dioguardi Histological Metriser machine allows to work at a speed of 0.1 mm^2/s, scanning a whole section in 6-8 ***： The results are the first standardized metrical evaluation of the geometric properties of the parenchyma, inflammation, fibrosis, and alterations in liver tissue tectonics of the biopsy sections. The present study confirms that biopsies are still valuable, not only for diagnosing chronic hepatitis, but also for quantifying changes in the organization and order of liver tissue structure.

关键词： Liver measurement Image analysis Liverlesion Liver tectonics

Correction of hypovitaminosis D improved global longitudinal strain earlier than left ventricular ejection fraction in cardiovascular older adults after orthopaedic surgery

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Journal of Geriatric Cardiology 2018年第8期15卷 519-522页

作者： Matteo Briguglio Luigi Gianturco Daniele Stellat Chiara Colombo Marika Bonadies Oscar Salat Mauro Anselmi Giuseppe Banff Maurizio Turiel Cardiology Unit IRCCS Orthopaedic Institute Galeazzi Milan Italy Scientific Direction IRCCS Orthopaedic Institute Galeazzi Milan Italy University Vitae Salute San Raffaele Milan Italy

Background Cardiovascular diseases and insufficient levels of vitamin D are risk factors for adverse surgical outcomes, and they are both commonly present among older adults undergoing orthopaedic surgery. Giving the cardiovascular effects of vitamin D, pre-operative diagnosis of hypovitaminosis D would be a valuable step for the implementation of supplementation protocols. We investigated if the nor- malization of serum 25 [OH] D could ameliorate cardiac performance of older adults suffering from cardiovascular diseases. Methods We enrolled 47 older adults scheduled for major orthopaedic surgery and suffering from hypovitaminosis D. Patients underwent 6-months cal- cifediol supplementation with a starting dose at first post-operative day of 50 ~tg/die in liquid preparation. Down-titration to 20 Ixg/die at 3-months assessment was planned. Cardiac performance was evaluated by measuring left ventricular ejection fraction （LVEF） and global longitudinal strain （GLS） during pre-operative assessments and at 1-month, 3-months, 6-months follow-ups. Results Six months of cal- cifediol supplementation were associated with a significant improvement of both LVEF （＋ 3.94%; 95% CI： -4.0789 to -0.8232; P 〈 0.01） and GLS （＋ 18.56%; Z = -5.895; P 〈 0.0001）. Conclusions Calcifediol supplementation normalized serum 25 [OH] D concentration after 1-month treatment. GLS offered better insights into myocardial contractile amelioration than LVEF, thus being useful for detecting earlier subclinical changes that may anticipate hemodynamic modifications.

关键词： Global longitudinal strain Left ventricular ejection fraction Orthopedic surgery Transthoracic echocardiography Vitamin D

Exercise-Dependent Modulation of Bone Metabolism and Bone Endocrine Function:New Findings and Therapeutic Perspectives

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Journal of Science in Sport and Exercise 2019年第1期1卷 20-28页

作者： Giovanni Lombardi irccs istituto ortopedico galeazzi Laboratory of Experimental Biochemistry and Molecular BiologyVia Riccardo Galeazzi420161 MilanItaly Department of Physiology and Pharmacology Gdańsk University of Physical Education and SportKazimierza Górskiego 180-336 GdańskPomorskiePoland

Physical inactivity is the fourth leading cause of mortality worldwide;regardless of geographic location and income,it is a contributing risk factor to the other three *** activity is really a drug,a poly-pill;its“regular use”can reduce this risk throughout the activation of a plethora of responses in virtually all the body *** beneficial effects of physi-cal activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle,adipose tissue and the immune system via the usage,delivery and distribution of metabolic substrates and improvement in inflammatory *** is emerging evidence for exercise-dependent changes in bone metabolism as well;with improved bone quality,reduced fracture risk and increased bone endocrine function,the last of which modulates energy metabolism through its effects on pancreatic islet cells,skeletal muscle and adipose *** endocrine function relies on the integration of biomechani-cal stimuli and endocrine signals from other organs and *** I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body *** molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and,among these,Wnt signaling,fibroblast growth factor-23,bone morphogenic protein-7,osteocalcin,RANK/RANKL/OPG axis,and lipocalin-2 gave the largest *** conclusion,beside the controversies surrounding technical aspects of the exercise,the efficacy of physi-cal activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.

关键词： Bone metabolism Bone endocrine function Osteokines Biomechanical loading

Proteomic insights on the metabolism in inflammatory bowel disease

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World Journal of Gastroenterology 2020年第7期26卷 696-705页

作者： Laura Francesca Pisani Manuela Moriggi Cecilia Gelfi Maurizio Vecchi Luca Pastorelli Gastroenterology and Digestive Endoscopy Unit IRCCS Policlinico San DonatoSan Donato Milanese 20097Italy Department of Biomedical Science for Health University of the Study of MilanIRCCS Istituto Ortopedico GaleazziMilan 20122Italy Gastroenterology and Endoscopy Unit IRCCS Ca'Granda FoundationPoliclinico HospitalUniversity of the Study of MilanMilan 20122Italy Department of Biomedical Science for Health University of the Study of MilanMilan 20122Italy

Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative *** pathogenesis of IBD is not completely unraveled,IBD are multi-factorial diseases with reported alterations in the gut microbiota,activation of different immune cell types,changes in the vascular endothelium,and alterations in the tight junctions’structure of the colonic epithelial *** represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal *** is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of *** a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful *** some non-invasive biomarkers have been described,none can be considered as the“gold standard”for IBD diagnosis,disease activity and therapy *** these reason new studies have proposed an“IBD signature”,which consists in a panel of biomarkers used to assess *** above described approach characterizes“omics”and in this review we will focus on proteomics.

关键词： Proteomics Inflammatory bowel disease Cronh’s disease Ulcerative colitis Proteins Biomarkers discovery