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Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

Cancer Drug Resistance 2022年第1期5卷 1-14页

作者： Lara Massai Damiano Cirri tiziano marzo Luigi Messori Department of Chemistry University of FlorenceSesto Fiorentino 50019Italy Department of Chemistry and Industrial Chemistry University of PisaPisa 56124Italy Department of Pharmacy University of PisaPisa 56126Italy CISUP-Centre for Instrumentation Sharing(Centro per l’Integrazione della Strumentazione Scientifica) University of PisaPisa 56126Italy University Consortium for Research in the Chemistry of Metal ions in Biological Systems(CIRCMSB) Bari 70126Italy

Today colorectal cancer(CRC)is one of the leading causes of cancer death *** disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely *** drugs,oxaliplatin in particular,were reported to produce some significant benefit in CRC treatment,triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC *** this frame,gold compounds and,specifically,the established antiarthritic drug auranofin with its analogs,form a novel group of promising anticancer *** to its innovative mechanism of action and its favorable pharmacological profile,auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment,capable of overcoming resistance to platinum *** encouraging results in this direction have already been obtained.A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug *** perspectives of the research in this field are outlined.

关键词： Auranofin CRC colorectal cancer metallodrugs anticancer agents gold gold-based drugs

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Contrasting demographic trends and asymmetric migration rates in a spatially structured amphibian population

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Integrative Zoology 2020年第6期15卷 482-497页

作者： Berta CAPELLÀ-marzo Gregorio SÁNCHEZ-MONTES Iñigo MARTÍNEZ-SOLANO Department of Biodiversity and Evolutionary Biology Museo Nacional de Ciencias NaturalesCSICMadridSpain

N_(a)tural populations often persist at the landscape scale as metapopulations,with breeding units(subpopulations)experiencing temporal extinction and recolonization *** parameters to forecast population viability in these systems include the ratio of the effective number of breeders(N_(b))to the total number of adults(N_(a))and migration rates among ***,we present the results of a 10-year integrative monitoring program of a metapopulation of the Iberian green frog(Pelophylax perezi)in central *** characterized population dynamics at two main breeding ponds(Gravera and Laguna)using capture-mark-recapture data to estimate N_(a)in each breeding season,and multilocus genotypes to estimate the effective population size(Ne),N_(b),individual breeding success,and migration *** ponds experienced population decline after a dry season,with Gravera subsequently recovering and Laguna suffering a bottleneck associated with genetic *** this subpopulation,average allelic richness and private alleles decreased from 2010(10.87 and 1.67,respectively)to 2018(8.0 and 0.20).The N_(b)/N_(a)ratio in Laguna in 2018 was twice as high(0.95)than in Gravera(0.41)or in pre-bottleneck Laguna(0.50),suggesting plasticity or genetic compensation through increased individual breeding *** rates were asymmetric between ponds,with a stronger contribution from Gravera to Laguna(29.9%vs.16.2%in the opposite direction)that may result in a rescue *** study emphasizes the importance of integrative demographic approaches for the monitoring of natural populations based on a better understanding of their spatio-temporal dynamics,which provides valuable information for conservation actions.

关键词： bottleneck capture-mark-recapture genetic monitoring metapopulation N_(b)/N_(a)ratio

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Use of micellar liquid chromatography for rapid monitoring of fungicides post harvest applied to citrus wastewater

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Journal of Environmental Sciences 2016年第4期28卷 284-292页

作者： Juan Peris-Vicente Ana marzo-Mas Pasqual Roca-Genovés Samuel Carda-Broch Josep Esteve-Romero Departamento de Quimica Fisica i Analitica ESTCE Universitat Jaume I 12071 Castello Spain

A method based on micellar liquid chromatography has been developed to simultaneously monitor four pesticides largely post-harvest applied to citrus：thiabendazole,pyrimethanil,o-phenylphenol and *** samples were filtered and directly injected without other treatment,thus avoiding extraction *** composition of the mobile phase was optimized using a chemometrical approach to achieve and excellent resolution to 0.07 mol/L SDS/5%,V/V 1-pentanol buffered at p H *** phase run through a C18 column at 1 m L/min at room *** detection was performing by UV–Visible absorbance using a wavelength program：0–10 min,305 nm（for thiabendazole）;10–12;265 nm（for pyrimethanil）and 12–18,220 nm（o-phenylphenol and imazalil）.The developed method was validated following the guidelines of the US Environmental Protection Agency in terms of：quantitation range,（0.5–4 to 15μg/m L）,linearity（r2〉0.9995）,sensitivity（LOD,0.18–1.4μg/m L）,precision（〈9.2%）,trueness（93.9%–103.7%）,and ruggedness（〈9.9%）.It was found that the fungicides remain up to eight days in surface water at outdoor *** method was used to screen the presence of the analytes in several waste water samples,and was proved to be useful in routine analysis.

关键词： Direct injection Micellar Pesticide Pollution Validation Water

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Molecular profiling of indolent human prostate cancer： tackling technical challenges to achieve high-fidelity genome-wide data

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Asian Journal of Andrology 2012年第3期14卷 385-392,I0005页

作者： Thomas A. Dunn Helen L. Fedor Angelo M. De marzo Jun Luo Department of Urology Johns Hopkins University Baltimore MD 21287 USA Department of Pathology Johns Hopkins University Baltimore MD 21287 USA

The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded （FFPE） tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

关键词： active surveillance formalin-fixed paraffin-embedded indolent prostate cancer microarray molecular profiling prostatecancer prostate cancer progression risk stratification

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Venous thromboembolism in patients with inflammatory bowel disease:Focus on prevention and treatment

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World Journal of Gastroenterology 2014年第12期20卷 3173-3179页

作者： Alfredo Papa Viviana Gerardi Manuela marzo Carla Felice Gian Lodovico Rapaccini Antonio Gasbarrini Internal Medicine and Gastroenterology Unit Catholic University

Inflammatory bowel disease(IBD)patients have an increased risk of venous thromboembolism(VTE),which represents a significant cause of morbidity and *** most common sites of VTE in IBD patients are the deep veins of the legs and pulmonary system,followed by the portal and mesenteric ***,other sites may also be involved,such as the cerebrovascular and retinal *** aetiology of VTE is multifactorial,including both inherited and acquired risk factors that,when simultaneously present,multiply the risk to the *** prevention involves correcting modifiable risk factors,such as disease activity,vitamin deficiency,dehydration and prolonged *** role of mechanical and pharmacological prophylaxis against VTE using anticoagulants is also ***,although guidelines recommend thromboprophylaxis for IBD patients,this method is still poorly implemented because of concerns about its safety and a lack of awareness of the magnitude of thrombotic risk in these *** efforts are required to increase the rate of pharmacological prevention of VTE in IBD patients to avoid preventable morbidity and mortality.

关键词： Inflammatory bowel disease Venous thromboembolism Thromboembolic prophylaxis Anticoagulants Unfractionated heparin Low molecular weight heparin

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Management of perianal fistulas in Crohn's disease:An upto-date review

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World Journal of Gastroenterology 2015年第5期21卷 1394-1403页

作者： Manuela marzo Carla Felice Daniela Pugliese Gianluca Andrisani Giammarco Mocci Alessandro Armuzzi Luisa Guidi IBD Unit Complesso Integrato ColumbusUniversità Cattolica del Sacro Cuore00168 RomeItaly

Perianal disease is one of the most disabling manifestations of Crohn's disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula *** medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.

关键词： Crohn’s disease Perianal fistula Surgery Drug ther

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HEART RATE VARIABILITY DURING HIGH-INTENSITY EXERCISE

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Journal of Systems Science & Complexity 2013年第1期26卷 104-116页

作者： SARMIENTO Samuel GARCIA-MANSO Juan Manuel MARTIN-GONZALEZ Juan Manuel VA-AMONDE Diana CALDERóN Javier DA SILVA-GRIGOLETTO marzo Edir Department of Physical Education University of Las Palmas de Gran Canaria Spain. Physics Department University of Las Palmas de Gran Canaria Spain. Department of Morphological Sciences School of Medicine University of Cdrdoba Spain. Physical Activity Sciences Faculty Polytechnic University of Madrid Spain. Andalusian Centre of Sports Medicine Cdrdoba Spain.

The aim of this paper is to describe and analyse the behaviour of heart rate variability(HRV)during constant-load,high-intensity exercise using a time frequency analysis(Wavelet Transform).Eleven elite cyclists took part in the study(age:18.6±3.0 years;VO_(2max):4.88±0.61 litres·min^(-1)).Initially,all subjects performed an incremental cycloergometer test to determine load power in a constant load-test(379.55±36.02 W;89.0%).HRV declined dramatically from the start of testing(p<0.05).The behaviour of power spectral density within the LF band mirrored that of total energy,recording a significant decrease from the outset LF peaks fell rapidly thereafter,remaining stable until the end of the ***-VHF fell sharply in the first 20 to 30 *** relative weighting(%) of HF-VHF was inverted with the onset of fatigue,[1.6%at the start,7.1(p<0.05) at the end of the first phase,and 43.1%(p<0.05) at the end of the test].HF-VHF_(peak) displayed three phases:a moderate initial increase,followed by a slight fall,thereafter increasing to the end of the *** LF/HF-VHF ratio increased at the start,later falling progressively until the end of the first phase and remaining around minimal values until the end of the test.

关键词： Cycling heart rate variability wavelet.

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Fear of COVID-19 and emotional dysfunction problems:Intrusive,avoidance and hyperarousal stress as key mediators

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World Journal of Psychiatry 2022年第8期12卷 1088-1101页

作者： Raquel Falcó Verónica Vidal-Arenas Jordi Ortet-Walker Juan C marzo JoséA Piqueras PSICO-RECURSOS COVID-19 Study Group Department of Health Psychology and Center for Applied Psychology Universidad Miguel HernándezElche 03202AlicanteSpain Department of Basic and Clinical Psychology and Psychobiology Universitat Jaume ICastellóde la Plana 12071CastellónSpain

BACKGROUND There is mounting empirical evidence of the detrimental effects of the coronavirus disease 2019(COVID-19)outbreak on mental *** research has underscored the effects of similar destabilizing situations such as war,natural disasters or other pandemics on acute stress levels which have been shown to exacerbate current and future psychopathological *** To explore the role of acute stress responses(intrusive,avoidance and hyperarousal)as mediators in the association between fear of COVID-19 and emotional dysfunction-related problems:Depression,agoraphobia,panic,obsessivecompulsive,generalized anxiety,social anxiety and health anxiety *** A sample of 439 participants from a university community in Spain(age:mean±SD:36.64±13.37;73.1%females)completed several measures assessing their fear of COVID-19,acute stress responses and emotional dysfunction syndromes through an online *** collection was carried out from the start of home confinement in Spain until May 4,2020,coinciding with initial de-escalation *** of the dataset included descriptive and frequency analyses,Mann-Whitney U Test of intergroup comparisons and path analysis for direct and indirect *** is an observational,descriptive-correlational and crosssectional *** The prevalence of clinical symptoms in our sample,reported since the beginning of the pandemic,reached 31.44%.The female group presented higher scores although the effect size was ***,the participants who exceeded the clinical cut-off points in emotional problems showed higher levels of fear of COVID-19 and of cognitive,motor and psychophysiological responses of acute stress,unlike the group with normative *** addition,the results show significant mediated effects of hyperarousal stress among fear of COVID-19 and emotional dysfunction ***,the clinical syndromes most related to the consequences of the pandemic(e.g.,social contact avoi

关键词： Fear of COVID-19 Acute stress Emotional dysfunction Psychophysiological activation Mediated effects

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Multiple Choice Tests: Inferences Based on Estimators of Maximum Likelihood

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Open Journal of Statistics 2014年第6期4卷 466-483页

作者： Pedro Femia-marzo Antonio Martín-Andrés Biostatistics Faculty of Medicine Department of Statistics and OR University of Granada Granada Spain

This paper revises and expands the model Delta for estimating the knowledge level in multiple choice tests (MCT). This model was originally proposed by Martín and Luna in 1989 (British Journal of Mathematical and Statistical Psychology, 42: 251) considering conditional inference. Consequently, the aim of this paper is to obtain the unconditioned estimators by means of the maximum likelihood method. Besides considering some properties arising from the unconditional inference, some additional issues regarding this model are also going to be addressed, e.g. test-inversion confidence intervals and how to treat omitted answers. A free program that allows the calculations described in the document is available on the website http://***.

关键词： Model Delta Multiple-Choice Tests Agreement Guessing

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Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19

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Journal of Geriatric Cardiology 2021年第5期18卷 338-345页

作者： Vincenzo De marzo Antonio Di Biagio Roberta Della Bona Antonio Vena Eleonora Arboscello Harusha Emirjona Sara Mora Mauro Giacomini Giorgio Da Rin Paolo Pelosi Matteo Bassetti Pietro Ameri Italo Porto GECOVID study group Cardiovascular Diseases Unit IRCCS Ospedale Policlinico San MartinoGenovaItaly Department of Internal Medicine University of GenovaGenovaItaly Infectious Diseases Unit IRCCS Ospedale Policlinico San MartinoGenovaItaly Department of Health Sciences University of GenovaGenovaItaly Emergency Department IRCCS Ospedale Policlinico San MartinoGenovaItaly Department of Informatics BioengineeringRobotics and System EngineeringUniversity of GenovaGenovaItaly Laboratory Unit IRCCS Ospedale Policlinico San MartinoGenovaItaly Anesthesia and Intensive Care Unit IRCCS Ospedale Policlinico San MartinoGenovaItaly Department of Surgical Sciences and Integrated Diagnostics University of GenovaGenovaItaly

BACKGROUND Increases in cardiac troponin(cTn)in coronavirus disease 2019(COVID19)have been associated with worse ***,data about the significance of cTn in elderly subjects with COVID19 are *** From a registry of consecutive patients with COVID19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020,we selected those≥60 yearold and with cTnI measured within three days from the molecular diagnosis of SARSCoV2 *** available,a second cTnI value within 48 h was also *** relationship between increased cTnI and allcause inhospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three *** Of 343 included patients(median age:75.0(68.0−83.0)years,34.7%men),88(25.7%)had cTnI above the upperreference limit(0.046μg/L).Patients with increased cTnI had more comorbidities,greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal ***,they died more(73.9%vs.37.3%,P<0.001)over 15(6−25)days of *** association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model(HR=1.61,95%CI:1.06−2.52,P=0.039)and was linear until 0.3μg/L,with a subsequent *** 191(55.7%)patients with a second cTnI measurement,49(25.7%)had an increasing trend,which was not associated with mortality(univariate HR=1.39,95%CI:0.87−2.22,P=0.265).CONCLUSIONS In elderly COVID19 patients,an initial increase in cTn is common and predicts a higher risk of *** cTn testing may not confer additional prognostic information.

关键词： patients mortality admitted

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