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Calcium-sensing receptor in colorectal inflammation and cancer:Current insights and future perspectives

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World Journal of Gastroenterology 2018年第36期24卷 4119-4131页

作者： luca Iamartino Taha Elajnaf Eniko Kallay Martin Schepelmann Institute of Pathophysiology and Allergy Research Medical University of ViennaVienna 1090Austria

The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the Ca SR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitisassociated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.

关键词： Calcium-sensing receptor Colon Cancer Inflammation Calcimimetics Calcilytics

Resilience of aging structures and infrastructure systems with emphasis on seismic resilience of bridges and road networks:Review

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Resilient Cities and Structures 2022年第2期1卷 23-41页

作者： luca Capacci Fabio Biondini Dan M.Frangopol Department of Civil and Environmental Engineering Politecnico di MilanoPiazza Leonardo da Vinci32Milan 20133Italy Department of Civil and Environmental Engineering ATLSS Engineering Research CenterLehigh University117 ATLSS Dr.BethlehemPA 18015-4729United States

Risk assessment and mitigation programs have been carried out over the last decades in the attempt to reduce transportation infrastructure downtime and post-disaster recovery ***,the concept of resilience gained increasing importance in design,assessment,maintenance,and rehabilitation structures and infrastructure systems,particularly bridges and transportation networks,exposed to natural and man-made *** the field of disaster mitigation,frameworks have been proposed to provide a basis for development of qualitative and quantitative models quantifying the functionality and resilience at various scales,including components,groups and systems within infrastructure networks and *** these frameworks,the effects of aging and environmental aggressiveness must be explicitly considered,affecting the structural performance and functionality of civil infrastructure *** efforts have been made to incorporate risk and resilience assessment frameworks into informed decision making to decide how to best use resources to minimize the impact of hazards on civil infrastructure *** review paper is part of these *** presents an overview of the main principles and concepts,methods and strategies,advances and accomplishments in the field of life-cycle reliability,risk and resilience of structures and infrastructure systems,with emphasis on seismic resilience of bridges and road networks.

关键词： Resilience Seismic hazards Aging structures Highway bridges Infrastructure systems

Do large brains of long-living mammals prefer non-newly generated,immature neurons？

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Neural Regeneration Research 2018年第4期13卷 633-634页

作者： Ottavia Palazzo Chiara La Rosa Matteo Piumatti luca Bonfanti Neuroscience Institute Cavalieri Ottolenghi(NICO) OrbassanoItaly institute of zoology-neurogenetics universitat regensburgGermany department of veterinary sciences university of turinGrugliasco(TO)Italy universitélibre de bruxelles(ulb) institute for interdisciplinary research in human biology(iribhm)BrusselsBelgium

Brain plasticity is heterogeneous in mammals：Brain regeneration and repair are the dream of every neurobiologist as well as every common citizen in the world who knows that most neurological diseases,dementia and other age-related problems affecting the central nervous system（CNS）do represent a heavy health and social *** re-generative processes are not＂ a natural property of the mammalian CNS, rather, due to evolutionary constraints they seem substantially reduced （if compared to those occurring in non-mammalian vertebrates） and hardly inducible by therapeutic approaches （reviewed in Martino et al., 2011）.

关键词： PSA Figure DCX Do large brains of long-living mammals prefer non-newly generated,immature neurons

Chronic hepatitis C,atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments?

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World Journal of Gastroenterology 2018年第41期24卷 4617-4621页

作者： Luigi Elio Adinolfi luca Rinaldi Riccardo Nevola Department of Medical SurgicalNeurologicalMetabolicand Geriatric SciencesUniversity of Campania "L.Vanvitelli"

Hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, among these there is an increased risk of atherosclerosis and cardiovascular disease as well as an increased cardiovascular mortality. Several direct and indirect HCV pro-atherogenic mechanisms have been proposed. HCV lives and replicates within carotid plaques, promoting a local environment of pro-atherogenic factors. In addition, it causes conditions such as insulin resistance, diabetes, hepatic steatosis, cryoglobulinemia and endotoxinemia that are associated with the development of atherosclerosis and cardiovascular disease. Therapeutic regimens based on direct-acting antiviral agents (DAA) are currently available with high efficacy in HCV clearance and improvement of liver disease, but does HCV eradication also improve atherosclerosis and the risk of cardiovascular disease? Recently, a multi-center study has shown that elimination of HCV improves carotid atherosclerosis. Two studies have shown that DAA treatments significantly reduce the risk of cardiovascular events. Several studies have assessed the impact of HCV clearance on pro-atherosclerosis metabolic conditions showing improvement in cardiovascular risk biomarkers, disappearance or improvement of insulin resistance, reduction of risk of developing diabetes and improvement of glycemic control. There are also evidences that HCV clearance promotes the recovery of cytokines and inflammatory markers associated with atherosclerosis and the disappearance of cryoglobulinemia. Available data show that clearance of HCV by DAAs is associated with an improvement in atherosclerosis and metabolic and immunological conditions that promote the development of cardiovascular disease. However, the data are not sufficient to allow definitive conclusions and further studies will be needed to definitively clarify the impact of HCV clearance on atherosclerosis and cardiovascular disease.

关键词： Direct-acting antiviral agents Hepatitis C virus Atherosclerosis Insulin resistance Cardiovascular disease

Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

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World Journal of Gastroenterology 2016年第38期22卷 8447-8458页

作者： Michele Merli Giuseppe Carli luca Arcaini Carlo Visco Division of Hematology University Hospital Ospedale di Circolo & Fondazione MacchiUniversity of Insubria Department of Cell Therapy and Hematology San Bortolo Hospital Department of Molecular Medicine University of Pavia

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

关键词： Non-hodgkin lymphomas Hepatitis C virus Antiviral therapy Interferon Ribavirin Sofosbuvir Direct-acting antiviral agents Marginal zone lymphomas

Partitioned and Monolithic Algorithms for the Numerical Solution of Cardiac Fluid-Structure Interaction

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Communications in Computational Physics 2022年第10期32卷 1217-1256页

作者： Michele Bucelli luca Dede Alfio Quarteroni Christian Vergara MOX Dipartimento di MatematicaPolitecnico di MilanoP.zza Leonardo da Vinci 3220133MilanItaly Mathematics Institute EPFLAv.PiccardCH-1015 LausanneSwitzerland(Professor Emeritus) LABS Dipartimento di ChimicaMateriali e Ingegneria Chimica“Giulio Natta”Politecnico di MilanoP.zza Leonardo da Vinci 3220133MilanItaly

We reviewand compare different fluid-structure interaction(FSI)numerical methods in the context of heart modeling,aiming at assessing their computational efficiency for cardiac numerical simulations and selecting the most appropriate method for heart *** dynamics within the human heart is characterized by active muscular action,during both contraction and relaxation phases of the *** efficient solution of the FSI problem in this context is challenging,due to the added-mass effect(caused by the comparable densities of fluid and solid,typical of biomechanics)and to the complexity,nonlinearity and anisotropy of cardiac consitutive *** this work,we review existing numerical coupling schemes for FSI in the two classes of strongly-coupled partitioned and monolithic *** schemes are compared on numerical tests that mimic the flow regime characterizing the heartbeat in a human ventricle,during both systole and *** mechanics is treated in both the active stress and active strain *** costs suggest the use of a monolithic *** employ it to simulate a full heartbeat of a human ventricle,showing how it allows to efficiently obtain physiologically meaningful results.

关键词： Heartmodeling activemechanics fluid structure interaction monolithic algorithms partitioned algorithms

Central pancreatectomy: The Dagradi Serio Iacono operation. Evolution of a surgical technique from the pioneers to the robotic approach

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World Journal of Gastroenterology 2014年第42期20卷 15674-15681页

作者： Calogero Iacono Andrea Ruzzenente luca Bortolasi Alfredo Guglielmi Department of Surgery Division of General Surgery "A" Unit of Hepato-Biliary-Pancreatic Surgery University of Verona Medical School "GB Rossi" University Hospital

Central pancreatectomy(CP) is a parenchyma-sparing surgical procedure. The aims are to clarify the history and the development of CP and to give credits to those from whom it came. Ehrhardt, in 1908, described segmental neck resection(SNR) followed, in 1910, by Finney without reconstructive part. In 1950 Honjyo described two cases of SNR combined with gastrectomy for gastric cancer infiltrating the neck of the pancreas. Guillemin and Bessot(1957) and Letton and Wilson(1959) dealt only with the reconstructive aspect of CP. Dagradi and Serio, in 1982, performed the first CP including the resective and reconstructive aspects. Subsequently Iacono has validated it with functional endocrine and exocrine tests and popularized it worldwide. In 2003, Baca and Bokan performed laparoscopic CP and, In 2004, Giulianotti et al performed a robotic assisted CP. CP is performed worldwide either by open surgery or by using minimally-invasive or robotic approaches. This confirms that the operation does not belong to whom introduced it but to everyone who carries out it; however credit must be given to those from whom it came.

关键词： Pancreatic history Pancreatic surgery Central pancreatectomy Conservative pancreatectomy

Is precision medicine for colorectal liver metastases still a utopia?New perspectives by modern biomarkers,radiomics,and artificial intelligence

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World Journal of Gastroenterology 2022年第6期28卷 608-623页

作者： luca Viganò Visala S Jayakody Arachchige Francesco Fiz Department of Hepatobiliary and General Surgery IRCCS Humanitas Research HospitalRozzano 20089MIItaly Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20072MIItaly Nuclear Medicine IRCCS Humanitas Research HospitalRozzano 20089MIItaly

The management of patients with liver metastases from colorectal cancer is still *** therapeutic options and treatment strategies are available for an extremely heterogeneous clinical *** prediction of patients’outcomes and of the effectiveness of chemotherapy and loco-regional treatments are crucial to reach a precision medicine *** has been an unmet need for a long time,but recent studies have opened new *** morphological biomarkers have been *** dynamic evaluation of the metastases across a time interval,with or without chemotherapy,provided a reliable assessment of the tumor *** have been explored and,thanks to their strong association with prognosis,have the potential to drive treatment *** liver-tumor interface has been identified as one of the main determinants of tumor progression,and its components,in particular the immune infiltrate,are the focus of major *** mining and analyses provided new insights on tumor biology and are expected to have a relevant impact on clinical *** intelligence is a further step *** present paper depicts the evolution of clinical decision-making for patients affected by colorectal liver metastases,facing modern biomarkers and innovative opportunities that will characterize the evolution of clinical research and practice in the next few years.

关键词： Colorectal liver metastases Biomarkers Genetics Immune infiltrate Radiomics Artificial Intelligence

Managing osteoporosis in ulcerative colitis: Something new?

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World Journal of Gastroenterology 2014年第39期20卷 14087-14098页

作者： luca Petruccio Piodi Alessandro Poloni Fabio Massimo Ulivieri Fondazione Irccs Ca’ Granda Ospedale Maggiore Policlinico of Milan 2nd Gastroenterology Unit 20122 Milan Italy Scuola di Specializzazione in Radiodiagnostica Università degli Studi di Milano Radiology Unit 20097 San Donato Milanese Italy Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico Nuclear MedicineBone Metabolic Unit 20122 Milan Italy

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX® tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other

关键词： Ulcerative colitis Osteoporosis Fragility fracture Bone mineral density Trabecular bone score Hip structural analysis Fracture assessment risk tool Dual energy X-ray absorptiometry