Evaluation of SCO1 deletion on Saccharomyces cerevisiae metabolism through a proteomic approach

The Saccharomyces cerevisiae gene SCO1 has been shown to play an essential role in copper delivery to cytochrome c oxidase. Biochemical studies demonstrated specific transfer of copper from Cox17p to Sco1p, and physical interactions between the Sco1p and Cox2p. Deletion of SCO1 yeast gene results in a respiratory deficient phenotype. This study aims to gain a more detailed insight on the effects of SCO1 deletion on S. cerevisiae metabolism. We compared, using a proteomic approach, the protein pattern of SCO1 null mutant strain and wild-type BY4741 strain grown on fermentable and on nonfermentable carbon sources. The analysis showed that on nonfermentable medium, the SCO1 mutant displayed a protein profile similar to that of actively fermenting yeast cells. Indeed, on 3% glycerol, this mutant displayed an increase of some glycolytic and fermentative enzymes such as glyceraldehyde-3-phosphate dehydrogenase 1, enolase 2, pyruvate decarboxylase 1, and alcohol dehydrogenase 1. These data were supported by immunoblotting and enzyme activity assay. Moreover, the ethanol assay and the oxygen consumption measurement demonstrated a fermentative activity in SCO1 mutant on respiratory medium. Our results suggest that on nonfermentable carbon source, the lack of Sco1p causes a metabolic shift from respiration to fermentation

Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography

Atypical presentation of ewing’s sarcoma with a single left orbital metastasis

BACKGROUND: We present an uncommon case of Ewing' sarcoma in a 16-year-old boy. CASE REPORT: This case can be considered unique because of the atypical presentation, normal laboratory tests and absence of the typical symptoms such as pain, masses or swelling, fatigue or weight loss, breathing problems linked to lung metastases or pathologic fractures. The only event that brought the patient to our attention was the sudden onset of left proptosis. CONCLUSIONS: The final histopathology together with CT and PET-CT findings led to the diagnosis of a multi-metastatic Ewing's sarcoma involving the orbit, skeleton, bone marrow and lymph nodes

Device's dehiscence 3 months after implant for mitral perivalvular leak

Our case is about a complication in a case of percutaneous closure of a perimitral leak in a patient with beleaflet mechanical mitral prosthesis. An Amplatzer vascular plug III was implanted. At the time of procedure the leak was successfully closed, however after three months a device's dehiscence developed. Percutaneous closure of mitral perivalvular leak is currently a feasible alternative in highly selected individuals, whose symptoms are not adequately palliated by medical therapy and who are at high surgical risk. Our case demonstrates that the presence of a wide calcification of the native annulus may represent a contraindication to this kind of treatment. Further studies on percutaneous approaches to perivalvular prosthetic regurgitation in presence of heavy calcification are needed, in order to define optimal patient selection and the late complications of this procedure. Moreover it will also be useful to design a device adapted for the anatomy of such defects in various sizes

The molecular mechanisms of antimetastatic ruthenium compounds explored through DIGE proteomics

<p>DIGE (difference in gel electrophoresis) proteomics is exploited here to gain insight into the molecular mechanisms of two established ruthenium-based antimetastatic agents, namely trans-[tetrachloro (DMSO) (imidazole)ruthenate(III)] (NAMI-A) and [Ru(eta(6)-toluene)Cl-2(PTA)] (RAPTA-T), where PTA is 1,3,5-triaza-7-phosphaadamantane. Following 24 h exposure of A2780/S human ovarian carcinoma cells to pharmacologically relevant concentrations of either ruthenium compound, 2D-DIGE proteomic analysis evidenced only few differentially expressed proteins with respect to controls. Successive mass spectrometry measurements, MALDI-TOF (matrix assisted laser desorption ionization-time of flight) or LC-ESI/MS-MS (liquid chromatography-electrospray ionization/multi-stage mass spectrometry), allowed identification of most altered protein spots, some of which were associated to perturbations in specific cellular functions. Direct insight into the cellular effects of the investigated metallodrugs is thus achieved. Notably, the patterns of protein alterations induced by NAMI-A and RAPTA-T are quite similar to each other while being deeply different from those of cisplatin. To the best of our knowledge this is the first proteomic study on human cancer cells investigating responses to antimetastatic ruthenium drugs. The key role of new "omic" approaches for deciphering the elusive and complex biochemical mechanisms through which anticancer metallodrugs produce their pharmacological effects is further documented. (C) 2012 Elsevier Inc. All rights reserved.</p>

Natural Active Ingredients for Poly (Lactic Acid)-Based Materials: State of the Art and Perspectives

This review describes the state of the art in the field of poly (lactic acid) (PLA)-based materials activated by natural compounds and extracts (active ingredients, AIs) from plant sources for food and biomedical applications. With a multidisciplinary approach, after a description of the synthesis and properties of PLA, special attention was paid to the chemical properties and unconventional extraction technologies of AIs used for PLA activation. Innovative techniques for the incorporation of AIs into PLA; characterization and the antioxidant and antimicrobial properties of the novel materials were discussed. In view of future perspectives, this study has evidenced that some aspects need to be further investigated from joint research between academia and industry, according to the green chemistry principles and circular economy strategy

Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds

Platinum-based chemotherapy is the primary treatment for human ovarian cancer. Overcoming platinum resistance has become a critical issue in the current chemotherapeutic strategies of ovarian cancer as drug resistance is the main reason for treatment failure. Cytotoxic gold compounds hold great promise to reach this goal; however, their modes of action are still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2-DE and MS analysis to identify differential protein expression in a cisplatin-resistant human ovarian cancer cell line (A2780/R) following treatment with two representative gold compounds, namely Auranofin and Auoxo6. It is shown that Auranofin mainly acts by altering the expression of Proteasome proteins while Auoxo6 mostly modifies proteins related to mRNA splicing, trafficking and stability. We also found that Thioredoxin-like protein 1 expression is greatly reduced after treatment with both gold compounds. These results are highly indicative of the likely sites of action of the two tested gold drugs and of the affected cellular functions. The implications of the obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold agents

Effects of Long COVID on Psycho-Physical Conditions in the Italian Population: A Statistical and Large Language Model Combined Description

Background: Long COVID refers to the persistence or development of signs and symptoms well after the acute phase of COVID-19. Objective of the study: To investigate the long-term outcomes of the SARS-CoV-2 infection in terms of psychological, social, and relational consequences within the Italian population. Materials and methods: We conducted an observational, cross-sectional, and multicenter study using an online questionnaire distributed to a sample of the Italian population. By utilizing the Short Form 12 Health Survey (SF-12) and the Hikikomori scale, we assessed perceived quality of life and social isolation, respectively. The questionnaire also included an open-answer question: “What will you remember about the pandemic period?”. We used generative artificial intelligence to analyze and summarize the corresponding answers. Results: A total of 1097 people participated in this study. A total of 79.3% (n = 870) of participants declared that they had been hospitalized and 62.8% (n = 689) received home care. Physical symptoms included headaches (43%, n = 472) and asthma (30.4%, n = 334). Additionally, 29.2% (n = 320) developed an addiction during the pandemic and, among these, 224 claimed internet addiction while 73 declared an emotional addiction. Furthermore, 51.8% (n = 568) experienced limitations in carrying out daily life activities. According to the Hikikomori scale, participants with positive SARS-CoV-2 infection exhibited higher levels of isolation compared to the others (p p < 0.001). Our semiautomatic analysis of the open-ended responses, obtained by a procedure based on a free large language model, allowed us to deduce and summarize the main feelings expressed by the interviewees regarding the pandemic. Conclusions: The data collected emphasize the urgent need to investigate the consequences of long COVID in order to implement interventions to support psychological well-being

Epidemiological Significance of SARS-CoV-2 RNA Dynamic in Naso-Pharyngeal Swabs

From 16 March to 15 December 2020, 132,357 naso-pharyngeal/oropharyngeal swabs were collected in the province of Teramo, Abruzzo Region, Italy, and tested for the presence of SARS-CoV-2 genomic RNA by a commercially available molecular assay. A total of 12,880 swabs resulted positive. For 8212 positive patients (4.150 women and 4.062 men) the median age was statistically different between women (median: 49.55 ± 23.9 of SD) and men (median: 48.35 ± 23.5 of SD) while no differences were found in the comparison between the cycle threshold for the N protein-encoding gene (CT N) median values and gender. Differences were observed in the CT N gene median values of swabs collected from March to September as well as in the pairwise comparison between September and October and between November and December. The CT N gene median values observed in specific periods characterizing the SARS-CoV-2 epidemic in 2020 were also compared with the incidence of COVID-19 cases; a strong inverse correlation was highlighted (Pearson correlation coefficient = −0.978). Our findings confirm the usefulness of the CT N values as an indirect detection parameter to monitor viral loads in the population

SARS-CoV-2 RNA Persistence in Naso-Pharyngeal Swabs

Since February 2020, Italy has been seriously affected by the SARS-CoV-2 pandemic. To support the National Health Care system, naso-pharyngeal/oropharyngeal swabs collected from suspected cases of Teramo province, Abruzzo region, are tested at Istituto Zooprofilattico Sperimentale dell&rsquo;Abruzzo e del Molise G. Caporale, for the presence of SARS-CoV-2 RNA. Out of 12,446 tested individuals, 605 returned positive results at least once, with prevalence significantly higher in men. A reduction of the level of viral RNA in the first swab per each positive patient collected over time was also observed. Moreover, 81 patients had at least one positive sample and two final negative tests: positivity in swabs lasted from 14 to 63 days, with a median value of 30 days. This shows the potential for the virus to coexist with patients for a long time, although we highlighted intermittent positivity in several cases. The evolution of the SARS-CoV-2 epidemiological situation and knowledge on viral shedding should be closely monitored, to interpret the findings correctly and adjust accordingly the surveillance activities