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Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

Journal of Molecular Cell Biology 2024年第3期16卷 9-23页

作者： Ilaria Frasson Linda Diamante manuela Zangrossi elena Carbognin Anna Dalla Pietà Alessandro Penna Antonio Rosato Ranieri Verin Filippo Torrigiani Cristiano Salata Marìa Paula Dizanzo Lorenzo Vaccaro Davide Cacchiarelli Sara N.Richter Marco Montagner Graziano Martello Department of Molecular Medicine University of PaduaPadua 35121Italy Department of Biology Armenise/Harvard Pluripotent Stem Cell Biology LaboratoryUniversity of PaduaPadua 35131Italy Department of Surgery Oncology and GastroenterologyUniversity of PaduaPadua 35128Italy Veneto Institute of Oncology IOV-IRCCS Padua 35128Italy Department of Comparative Biomedicine and Food Science University of PaduaPadua 35020Italy Telethon Institute of Genetics and Medicine(TIGEM) Armenise/Harvard Laboratory of Integrative GenomicsPozzuoli 80078Italy Department of Translational Medicine University of Naples Federico IINaples 80138Italy School for Advanced Studies Genomics and Experimental Medicine ProgramUniversity of Naples Federico IINaples 80138Italy Microbiology and Virology Unit Padua University HospitalPadua 35128Italy

The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral *** host dependency factors,*** proteins required for viral replication,would help prevent the development of ***,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host *** this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and *** regularly interspaced short palindromic repeats screening identified host genes required for each variant during *** of the genes were shared by multiple *** validated our hits with small molecules and repurposed the US Food and Drug Administration-approved *** the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral *** such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse *** study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.

关键词： SARS-CoV-2 variants of concern host dependency factors antivirals N-acetyl cysteine

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Postmortem Nasopharyngeal Swabs Performed during the COVID-19 Infection:Analysis of Preliminary Clinical Records by the Genoa Institute of Legal Medicine(North-West Italy)

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Journal of Forensic Science and Medicine 2022年第1期8卷 24-31页

作者： Martina Drommi Rosario Barranco Arianna Bal bo Stefano Errico Francesca Maria elena Frigiolini manuela Mangioni Giulia Molinari Alessandra Zappi Patrizia Caligiuri Francesco De Stefano Francesco Ventura Department of Forensic and Legal Medicine University of GenovaGenovaItaly Department of Health Sciences University of GenovaGenoaItaly Department of Hygiene San Martino Polyclinic HospitalGenovaItaly

COVID-19,the disease caused by the SARS-CoV-2 virus,is highly *** persistence of the virus after infected individuals die remains *** article reports the findings taken from postmortem nasopharyngeal swabs performed to investigate the presence of SARS-CoV-2 in the corpses transferred to the Genoa District Mortuary from the outset of the Italian lockdown(March 9)to the end of the first emergency phase(July 13).One hundred and eighty swabs were carried out:13 corpses resulted positive for the virus,with the diagnosis being reached only after *** were male and 6 female with an average age of 73.5 years *** most frequent comorbidities recorded were arterial hypertension,diabetes,Alzheimer 5s,and pulmonary *** two cases,the swab tested positive at a distance of 125 h and 165 h from actual *** nasopharyngeal swab results a useful way to screen corpses for COVID-19 and to handle bodies in Legal Medicine Centers where safe autoptic rooms are not *** are also a means of safeguarding forensic pathologists,identifying the presence of breeding grounds in the community and providing information for the Public Prosecutor's Office in legal *** are able to produce reliable results up to at least 7 days following death,provided that the corpse is correctly preserved.

关键词： Autopsy forensic pathology legal medicine managing of the corpses naso-pharyngeal swab SARS-CoV-2

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Modulation Possibilities of the Tissue Wettability, Marker of the Physical Modifications Produced by Senescence versus Photo Senescence at Tegument Level

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Journal of Biomedical Science and Engineering 2014年第13期7卷 1049-1055页

作者： Laurentiu Badescu Carmen elena Cotrutz Raoul Lupusoru Bogdan-Mihail Diaconescu manuela Ciocoiu Magda Badescu Department of Cell and Molecular Biology University of Medicine and Pharmacy “Grigore T. Popa” Iasi Romania Department of Pathophysiology University of Medicine and Pharmacy “Grigore T. Popa” Iasi Romania Department of Pathophysiology University of Medicine and Pharmacy “Grigore T. Popa” Iasi Romania

We used an experimental model involving white Westar rats (young and old) who were subjected to precise doses of ultraviolet radiation (UV). The experiment aims to examine the influence of epidermis potential protection factors in photo senescence versus senescence. We have studied the in vivo effect of some natural polyphones extracted from black grapes seeds and zinc aspartate and in vitro effect of AED (deuterium depleted water). The substances were administered by intragastric gavages, at two days intervals for two weeks prior to UV irradiation and during the entire period of the experiment (28 days). In the end, we determined the degree of hydrophilicity of the skin, in vitro, by measuring the contact angle value, which was inversely proportional to the hydrophilicity of the tissue (the angle formed at the contact between a liquid and a solid surface). Using this method we found a large variability depending on the hydrophilicity of the epidermis (abdomen and back), the age of the animal and UV/non UV irradiation. The maintenance of the epidermis fragments in AED (for 6 hours) increased significantly the tissue wet ability degree both in the young rats subject to UV and in the senescent ones subject to UV (photo senescence).

关键词： Skin Photoimmunology Phototherapy

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Evaluation of the Controlled Release Ability of Theophylline from Xanthan/Chondroitin Sulfate Hydrogels

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Journal of Biomaterials and Nanobiotechnology 2013年第2期4卷 123-131页

作者： Ana-Maria Oprea manuela-Tatiana Nistor Lenuta Profire Marcel Ionel Popa Catalina elena Lupusoru Cornelia Vasile Department of Pharmacology and Algesiology “Gr. T. Popa” Medicine and Pharmacy University Iasi Romania Department of Physical Chemistry of Polymers Romanian Academy “P. Poni” Institute of Macromolecular Chemistry Iasi Romania Faculty of Chemical Engineering and Environmental Protection “Gh. Asachi” Technical University Iasi Romania

The xanthan/chondroitin sulfate (X/CS) hydrogels, obtained by a crosslinking technique, were evaluated in vitro and in vivo as matrices for theophylline release. The influence of pH of simulated physiological media on the X/CS swelling behaviour at 37°C was investigated. The hydrogels theophylline loading degree was evaluated by near infrared chemical imaging (NIR-CI) technique and confirmed also by FT-IR spectroscopy;the drug loading was about 77.5% based on PLS-DA prediction (Partial least squares-Discriminate Analysis). The release profiles of theophylline from X/CS hydrogels in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) depend on CS content. The release mechanisms were controlled by the drug solubility and ionic properties of the polymers. In vivo theophylline delivery was done by oral administration. Pharmacokinetic analysis revealed sustained-release characteristics for 50/50 X/CS theophylline-loaded formulation compared with raw theophylline which was rapidly absorbed, distributed and eliminated. A good in vitro-in vivo correlation was found.

关键词： Polysaccharide Hydrogels Theophylline Swelling In Vitro/In Vivo Release Pharmacokinetics

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Risk factors distribution and cardiovascular disease prevalence in the Italian population: The CHECK study

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Open Journal of Epidemiology 2012年第4期2卷 90-100页

作者： elena Tragni Alessandro Filippi manuela Casula Giampiero Favato Ovidio Brignoli Claudio Cricelli Andrea Poli Alberico L. Catapano Epidemiology and Preventive Pharmacology Centre (SEFAP) University of Milano Milano Italy IRCCS Multimedica Sesto S. Giovanni Milano Italy Italian Society of General Medicine (SIMG) Firenze Italy Kingston University Kingston upon Thames UK

Objective: To evaluate the distribution of cardiovascular risk factors and the prevalence of cardiovascular disease in a sample of the Italian population. Methods: CHECK (Cholesterol and Health: Education, Control and Knowledge) is a cross-sectional observational study in a randomised sample of the Italian adult population aged 40 - 79 years, in the setting of general practice. Results: 5846 subjects (50.3% male) were included in the analysis. The mean age [±SD] of the observed cohort was 57.8 (±10.3) years. One out of five subjects smoked cigarettes and almost 80% didn’t engage in regular leisure-time physical activity. The mean blood pressure was 132.0 [±14.7]/81.2 [±7.9] mmHg. The total and LDL-cholesterol levels were respectively 205.3 [±35.9] mg/dL and 124.9 [±29.9] mg/dL. The mean glucose concentration was 98.3 [±28.2] mg/dL. The prevalence rate of hypertension, hypercholesterolemia, and type 2 diabetes were respectively 51.8%, 55.6%, and 13.0%. 8.9% of the observed subjects had a history of cardiovascular events, while in the primary prevention group the 10-year-risk of coronary heart disease (Framingham algorithm) was 10.1% [±8.3%] and of cardiovascular disease (CUORE algorithm) was 5.2% [±5.9%]. Conclusion: The CHECK study provides a detailed description of a randomised sample of the Italian population, contributing to evaluate the prevalence of cardiovascular risk factors and the main cardiovascular disease in Italy and to provide a baseline to set priorities and objectives for future intervention of health policy.

关键词： Italian Population Epidemiological Study Cardiovascular Risk Factors Prevalence of Cardiovascular Disease

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Evaluation of the Efficacy of 99.9% Pure Silver Trilaminate Cups in the Prevention and Treatment of Nipple Pain and Fissures

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Open Journal of Nursing 2023年第10期13卷 686-698页

作者： Monica Pilloni Pierina Zedda Carla Orrù elena Fassina Maria Carmela Forte Rossana Mazzulla Brunella Celestino Maria Francesca Marotto manuela Neri Gian Benedetto Melis Anna Maria Paoletti University Hospital of Cagliari (UHC) Cagliari Italy Department of Surgical Sciences University of Cagliari Cagliari Italy Maternal and Child Family Counselling Quartu Sant’Elena Cagliari Italy Caruso’s Medical Office Cusago Italy Hospital of Castrovillari Cosenza Italy Hospital of Cosenza Cosenza Italy Maternal and Child Family Counselling Argentano Cosenza Italy Company of National Importance and High Specialization (CNIHS) Giovanni Brotzu Cagliari Italy Women’s Wellness Foundation Cagliari Italy

Breastfeeding is drastically decreasing over time and nipple trauma constitutes one of the most significant reasons for its discontinuation. In this context, this study aimed at evaluating the effectiveness and tolerability of a topical treatment device, namely Silver Cap® (Depofarma S.P.A.), when used to prevent pain and nipple fissure formation. The medical device consists in a silver trilaminate cup to be placed on the nipple, providing physical protection and creating a moist environment. The study involved 187 women: 38 started to apply the device prior to lactation (PL group) and 149 during lactation (DL group). Aiming to collect safety and performance data, both groups were provided with questionnaires during 6 consecutive visits (120 days of follow-up). At last visit, absence of painful symptoms was reported by the 98.8% and the 100% of women in DL and PL groups, respectively. Moreover, no nipple fissures were observed and no adverse events directly correlated to use of the device were reported. According to these findings, it can be concluded that Silver Cap® is a safe and effective device for nipple pain and fissure prevention. .

关键词： Silver Cap Breastfeeding Breast Pain Nipple Fissures

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Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma

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World Journal of Gastroenterology 2007年第37期13卷 4986-4995页

作者： Guido Rasi Annalucia Serafino Lia Bellis Maria Teresa Lonardo Federica Andreola manuela Zonfrillo Giovanni Vennarecci Pasquale Pierimarchi Paola Sinibaldi Vallebona Giuseppe Maria Ettorre Eugenio Santoro Claudio Puoti Institute of Neurobiology and Molecular Medicine National Research Council Rome Italy Hepatic Haemodynamic Unit Marino Hospital Rome Italy Division of Surgical Oncology and Liver Transplantation Regina Elena Cancer Institute Rome Italy Department of Experimental Medicine and Biochemical Science University of Rome "Tor Vergata" Rome Italy Department of Internal Medicine and DigestiveDiseases Marino Hospital Rome Italy

AIM: To define NGF (nerve growth factor) and its high- affinity receptor trkANGF presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC. METHODS: Intracellular distribution of NGF and trkANGF were assessed by immunohistochemistry and immuno- electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels. RESULTS: NGF and trkANGF were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkANGF were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls. CONCLUSION: NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.

关键词： Nerve growth factor Hepatocellular carcinoma Liver cirrhosis Confocal microscopy Transmission electron microscopy

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Risk of Upper Extremity Biomechanical Overload in Automotive Facility

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Biomedical and Environmental Sciences 2013年第1期26卷 70-75页

作者： Angela SANCINI Assunta CAPOZZELLA Tiziana CACIAR Francesco TOMEI Nadia NARDONE Barbara SCALA Maria FIASCHETTI Carlotta CETICA Lara SCIMITTO PierAgostino GIOFFRè Federica SINIBALDI Claudia Di PASTENA Paola CORBOSIERO Maria Pia SCHIFANO Gianfranco TOMEI manuela CIARROCCA University of Rome "Sapienza" Department of AnatomyHistologyMedical-Legal and OrthopedicsUnit of Occupational MedicineViale Regina Elena 33600161 RomeItaly University of Rome "Sapienza" Department of Psychiatric and Psychological SciencePiazzale Aldo Moro 500185 RomeItaly

Objective To assess the risk factors for upper extremity-work-related musculoskeletal disorders（UE-WMSD） on 13 prod ucti on lines in an airbag factory using the threshold limit values-American conference of industrial hygienists-hand activity level（TLV-ACGIH-HAL） method and introduce the ergonomic improvement to reduce the repe titi veness and the peak force（Pf）.Methods Professional exposure level on 13 production lines in a automobile factory was measured using the TLV-ACGIH-HAL method and a further risk was assessed according to the ergonomic *** The first assessment of 9 produc tion lines showed that the professional exposure level was above the TLV or HAL *** second assessment showed that the professional exposure level was below the AL limit on all production lines except 1,in which the professional exposure level was between TLV and *** The assessment of UE-WMSD-related risk can ide ntif y the riskiest emplacements and evaluate the reduc tion of risk in professional exposure through interventi ons of structuralorganizati onal type.

关键词： Repe titi ve acti vity Work-related musculoskeletal disorders Assessment of work-related risk Threshold limit values-American conference of industrial hygienists Hand activity level.

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