Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS

<p>Abstract</p> <p>Background</p> <p>Treatment of feline immunodeficiency virus (FIV) infection has been hampered by the absence of a specific combination antiretroviral treatment (ART). Integrase strand transfer inhibitors (INSTIs) are emerging as a promising new drug class for HIV-1 treatment, and we evaluated the possibility of inhibiting FIV replication using INSTIs.</p> <p>Methods</p> <p>Phylogenetic analysis of lentiviral integrase (IN) sequences was carried out using the PAUP* software. A theoretical three-dimensional structure of the FIV IN catalytic core domain (CCD) was obtained by homology modeling based on a crystal structure of HIV-1 IN CCD. The interaction of the transferred strand of viral DNA with the catalytic cavity of FIV IN was deduced from a crystal structure of a structurally similar transposase complexed with transposable DNA. Molecular docking simulations were conducted using a genetic algorithm (GOLD). Antiviral activity was tested in feline lymphoblastoid MBM cells acutely infected with the FIV Petaluma strain. Circular and total proviral DNA was quantified by real-time PCR.</p> <p>Results</p> <p>The calculated INSTI-binding sites were found to be nearly identical in FIV and HIV-1 IN CCDs. The close similarity of primate and feline lentivirus IN CCDs was also supported by phylogenetic analysis. In line with these bioinformatic analyses, FIV replication was efficiently inhibited in acutely infected cell cultures by three investigational INSTIs, designed for HIV-1 and belonging to different classes. Of note, the naphthyridine carboxamide INSTI, L-870,810 displayed an EC₅₀in the low nanomolar range. Inhibition of FIV integration <it>in situ </it>was shown by real-time PCR experiments that revealed accumulation of circular forms of FIV DNA within cells treated with L-870,810.</p> <p>Conclusion</p> <p>We report a drug class (other than nucleosidic reverse transcriptase inhibitors) that is capable of inhibiting FIV replication <it>in vitro</it>. The present study helped establish L-870,810, a compound successfully tested in human clinical trials, as one of the most potent anti-FIV agents ever tested <it>in vitro</it>. This finding may provide new avenues for treating FIV infection and contribute to the development of a small animal model mimicking the effects of ART in humans.</p

Human Arboviral Infections in Italy: Past, Current, and Future Challenges

: Arboviruses represent a public health concern in many European countries, including Italy, mostly because they can infect humans, causing potentially severe emergent or re-emergent diseases, with epidemic outbreaks and the introduction of endemic circulation of new species previously confined to tropical and sub-tropical regions. In this review, we summarize the Italian epidemiology of arboviral infection over the past 10 years, describing both endemic and imported arboviral infections, vector distribution, and the influence of climate change on vector ecology. Strengthening surveillance systems at a national and international level is highly recommended to be prepared to face potential threats due to arbovirus diffusion

Validation of the T-Lymphocyte Subset Index (TLSI) as a Score to Predict Mortality in Unvaccinated Hospitalized COVID-19 Patients

Lymphopenia has been consistently reported as associated with severe coronavirus disease 2019 (COVID-19). Several studies have described a profound decline in all T-cell subtypes in hospitalized patients with severe and critical COVID-19. The aim of this study was to assess the role of T-lymphocyte subset absolute counts measured at ward admission in predicting 30-day mortality in COVID-19 hospitalized patients, validating a new prognostic score, the T-Lymphocyte Subset Index (TLSI, range 0–2), based on the number of T-cell subset (CD4+ and CD8+) absolute counts that are below prespecified cutoffs. These cutoff values derive from a previously published work of our research group at Policlinico Tor Vergata, Rome, Italy: CD3+CD4+ &lt; 369 cells/µL, CD3+CD8+ &lt; 194 cells/µL. In the present single-center retrospective study, T-cell subsets were assessed on admission to the infectious diseases ward. Statistical analysis was performed using JASP (Version 0.16.2. JASP Team, 2022, The Amsterdam, The Netherlands) and Prism8 (version 8.2.1. GraphPad Software, San Diego, CA, USA). Clinical and laboratory parameters of 296 adult patients hospitalized because of COVID-19 were analyzed. The overall mortality rate was 22.3% (66/296). Survivors (S) had a statistically significant lower TLSI score compared to non-survivors (NS) (p &lt; 0.001). Patients with increasing TLSI scores had proportionally higher rates of 30-day mortality (p &lt; 0.0001). In the multivariable logistic analysis, the TLSI was an independent predictor of in-hospital 30-day mortality (OR: 1.893, p = 0.003). Survival analysis showed that patients with a TLSI &gt; 0 had an increased risk of death compared to patients with a TLSI = 0 (hazard ratio: 2.83, p &lt; 0.0001). The TLSI was confirmed as an early and independent predictor of COVID-19 in-hospital 30-day mortalit

Marine anticancer agents: An overview with a particular focus on their chemical classes

UID/Multi/04378/2019 IF/00700/2014 grant number 216Z167 grant RTA 2015-00010-C03-02 No. PBA/MB/16/01 PDOC/19/02/01The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.publishersversionpublishe

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

The European Emission Trading System and its followers: Comparative analysis and linking perspectives

During the past decades there has been a wide debate on which economic instruments are more suitable to fight climate change in a way that is both economically efficient and legally rigorous. Among the various instruments, Emission Trading has gained increasing importance worldwide. Following the example of the European Emission Trading System (henceforth EU ETS), which set up in 2005 the first international carbon market, many other countries have decided to set up their own ETS at the national or regional level, generating a sort of rapid sprawling of the ETSs around the world. Given the difficulties encountered in the post-Kyoto phase (and actually during the Kyoto phase too) to pursue a multilateral solution to climate change problems, many scholars and policy-makers started looking at linking ETSs as a possible way to progressively achieve a common instrument to reduce polluting emissions. Linking ETSs implies deep economic and legal difficulties: it requires a rigorous legal framework for its proper economic functioning. Still, it might become one of the main routes to fight climate change in the near future. To get a deeper understanding on this issue, this book provides a detailed analysis of the main ETSs from both the legal and economic perspectives with the intent to compare their features and examine whether and how to link them in the future. It is the effort of a joint legal and economic team based at the University of Siena where we collaborate within the research group R4S-Regulation for Sustainability

The Impact of Social Enterprises: A Bibliometric Analysis From 1991 to 2020

The aim of this work is to provide, through a bibliometric analysis of the last 30 years of thematic literature, an overview on the contribution of social enterprises to the achievement of global goals. A bibliometric method has been used to analyze the characteristics, citation patterns and content of 3318 documents published in international academic journals, books review and chapters, editorial material and proceedings papers. Considering our findings, the bibliometric analysis has shown that there are journals that have had a greater production on the topic with an impact on research. Thanks to the work of the most impactful authors, it emerges that the case study is the most used method to demonstrate the centrality of social enterprises in social innovation. The analysis also shows that the centrality of the themes is linked to innovation, impact, management and performance, demonstrating the assumption that the driver of innovation in terms of social impact is given by these types of companies. The research also shows the keyword evolution through the years. Through the coding activity, it has also been possible to demonstrate that by transposing the global sustainability objectives to the local that the more in-depth ones are addressed on the issues of sustainable economy and fair, responsible and sustainable innovation, while there is much shortcoming regarding the achievement of gender equality, sustainable water management but even more on the reduction of inequality between nations. The latter is probably conditioned by the more global target and therefore not easily approachable to social enterprises

I tumori cistici del pancreas. Revisione della letteratura e proposta di un percorso diagnostico-terapeutico

In questo lavoro, gli Autori esaminano gli aspetti epidemiologici, clinici, anatomo-patologici, morfologico-strumentali e chimico-fisici propri di ogni singolo tipo di lesione cistica del pancreas e li paragonano tra di loro in maniera critica. In tal modo riescono ad individuare per ogni singola categoria le caratteristiche più salienti. Un percorso composto di quattro gruppi principali di esami strumentali e di laboratorio (ecografia addominale standard / EUS, TC, RM, FNA / biopsia / dosaggio di oncomarkers ed amilasi del contenuto cistico) è stato prescelto per l’acquisizione di tutti questi dati in virtù di precisi criteri di specificità, sensibilità ed accuratezza diagnostica forniti dalla letteratura scientifica internazionale. Per ogni sottogruppo di tumore cistico del pancreas viene proposto, infine, il piano terapeutico accreditato di miglior successo, sempre secondo la comune opinione scientifica internazional