Search

Since Paul Ehrlich’s introduction of the “magic bullet” concept in 1908, drug developers have been seeking new ways to target drug activity to diseased cells while limiting effects on normal tissues. In recent years, it has been proposed that coupling riboswitches capable of detecting RNA biomarkers to small interfering RNAs (siRNAs) to create siRNA pro-drugs could selectively activate RNA interference (RNAi) activity in specific cells. However, this concept has not been achieved previously. We report here that we have accomplished this goal, validating a simple and programmable new design that functions reliably in mammalian cells. We show that these conditionally activated siRNAs (Cond-siRNAs) can switch RNAi activity against different targets between clearly distinguished OFF and ON states in response to different cellular RNA biomarkers. Notably, in a rat cardiomyocyte cell line (H9C2), one version of our construct demonstrated biologically meaningful inhibition of a heart-disease-related target gene protein phosphatase 3 catalytic subunit alpha (PPP3CA) in response to increased expression of the pathological marker atrial natriuretic peptide (NPPA) messenger RNA (mRNA). Our results demonstrate the ability of synthetic riboswitches to regulate gene expression in mammalian cells, opening a new path for development of programmable siRNA pro-drugs.

RB1 mutations are seen in 40-60% of sporadic osteosarcoma. Here, the authors demonstrate a selective sensitivity to PARP inhibitors in RB1-mutated osteosarcoma-derived cell lines that is not associated with canonical signatures indicative of a homologous recombination defect.

Global warming is affecting habitat quality and availability on our planet and some species are predicted or are by now changing their distribution range. Here we show that loggerhead turtles have already started to expand their nesting range into the Western Mediterranean, which has until recently hosted only sporadic nests. We compiled information on nesting activity from beaches surrounding the Western Mediterranean and collected metadata on loggerhead turtle nests in Spain, France, Italy, and Tunisia between 2010 and 2020 to provide an exhaustive overview on the phenomenon of emerging new nest sites for loggerhead turtles. The number of recorded nests has increased drastically since 2013 from 1 to 3 nests/year to a record number of 84 registered in 2020. While this increase may partly be explained by grown awareness and reporting by citizens, there is no doubt of an upward trend in nesting activity. The nests are unevenly distributed over the study area with most nests occurring on the coasts of the warmer Tyrrhenian Sea. A hotspot analysis identified beaches in SW Italy, SE Sardinia, and NW Tunisia with statistically significant clustering of nests. Within these hotspots, three beaches in SW Italy and one in Tunisia had nests at least four out of the five last years. Nesting phenology corresponds to that of Eastern Mediterranean rookeries, and mean hatching success of naturally incubating, non-manipulated nests was 66 %, although there was variability across the region. Mean incubation durations also varied between countries indicating a diversity in inferred sex ratios, with sufficient female production to foster future colonisation of this region. Unfortunately, these beaches are already under high tourist pressure and subject to intense coastal development, imposing many threats to the females, eggs, and hatchlings. Thus, while this study reveals the unique opportunity to witness and study an ongoing new colonisation process in loggerhead turtles, it also calls for urgent proactive conservation actions to mitigate these threats and allow the turtles to establish new rookeries.

The Mediterranean Diet plays a critical role in the prevention of primary cardiovascular disease (CVD). Actually, there is a scarcity of evidence for secondary prevention. The current study aims to assess adherence to the Mediterranean diet (MD) in patients recently admitted to the Cardiac Rehabilitation Unit following acute cardiovascular disease. Adherence to MD was assessed in 111 patients admitted to the Cardiac Rehabilitation Unit of the Federico II Hospital in Naples. The Medi-Lite score was used to assess adherence to MD. The main determinant of reduced MD compliance was assessed using Pearson’s correlation analysis and a multivariable regression model. The population had a median MD adherence score of 11 and a mean score of 10.9. The lowest possible score was 5 (indicating poor adherence), and the highest possible score was 15 (excellent adherence index). There were 3 participants with a poor score (

Salmonella is one of the most common agents of foodborne illness. The genus Salmonella includes two species (Salmonella bongori and S. enterica) and six subspecies (enterica I, salamae II, arizonae IIIa, diarizonae IIIb, houtenae IV, and indica VI), each of which contains multiple serotypes associated with animal and human infections. The aim of the study was to evaluate the presence of Salmonella spp. in carcasses of food-producing animals and foods in southern Italy and the serovar distribution among different sources. From 2011 to 2021, a total of 12,246 foods and 982 samples from animal carcasses were collected and analyzed. The overall percentage of positive samples was 5.84% (N = 773) and a significant increase in prevalence was observed by comparing the years 2011–2015 (257, 3.27%) and 2016–2021 (516, 9.61%; p < 0.05). The highest percentage of positive food samples was observed in “Meat and Meat Products” (N = 327/2,438, 13.41%) followed by “Fish and fishery products” (N = 115/1,915, 6.01%). In carcasses, the highest percentage of positive samples was reported from broilers (N = 42/81, 51.85%) followed by buffalo (N = 50/101, 49.50%) and pork (N = 140/380, 36.84%). After typing, the isolates were assigned to the species S. enterica and to the subspecies: enterica (N = 760, 98.32%), diarizonae (N = 8, 1.03%), salamae (N = 3, 0.39%) and houtenae (N = 2, 0.26%). S. Infantis was the most frequently detected (N = 177, 24.76%), followed by S. Derby (N = 77, 10.77%), monophasic S. Typhimurium (N = 63, 8.81%), S. Typhimurium (N = 54, 7.55%), and S. Rissen (N = 47, 6.57%). By comparing the sampling period 2011–2015 with that of 2016–2021, an increase in the prevalence of S. Infantis and monophasic S. Typhimurium and a decrease of S. Typhimurium were recorded (p < 0.05). Thus, present data suggest that, despite the implementation of national and European control strategies to protect against Salmonella, the prevalence of this pathogen in southern Italy is still increasing and a change of national control programs to protect against Salmonella are necessary.

This study employs a life cycle assessment (LCA) approach to investigate the environmental burden of photovoltaic power generation systems that use multi-crystalline silicon (multi-Si) modules in Pakistan. This study evaluates the energy payback time (EPBT) of this class of systems, and considers various environmental impacts, including climate change, acidification, and eutrophication. The assessment accounts for upstream, midstream, and downstream processes, including cell as well as module production. The critical stages in the production cycle were identified, including the metallic silicon transformation into solar silicon and the assembly of the panels, which involve energy-intensive materials such as aluminum frames and glass roofing. Despite using the most efficient conversion technology, the former stage consumes a significant amount of electricity. This study reveals that multi-Si PV systems in Pakistan have an EPBT that is considerably less than their lifespan, ranging from 2.5 to 3.5 years. These findings suggest that the development of PV systems in Pakistan is a very interesting option for energy production. Additionally, this study compares solar PV and wind power generation systems in various regions of Pakistan. The study outcomes can facilitate evidence-based decision-making processes in the renewable energy sector and contribute significantly to Pakistan’s endeavor to transition toward a sustainable energy system.

SARS-CoV-2 can be detected in the feces of infected people, consequently in wastewater, and in bivalve mollusks, that are able to accumulate viruses due to their ability to filter large amounts of water. This study aimed to monitor SARS-CoV-2 RNA presence in 168 raw wastewater samples collected from six wastewater treatment plants (WWTPs) and 57 mollusk samples obtained from eight harvesting sites in Campania, Italy. The monitoring period spanned from October 2021 to April 2022, and the results were compared and correlated with the epidemiological situation. In sewage, the ORF1b region of SARS-CoV-2 was detected using RT-qPCR, while in mollusks, three targets—RdRp, ORF1b, and E—were identified via RT-dPCR. Results showed a 92.3% rate of positive wastewater samples with increased genomic copies (g.c.)/(day*inhabitant) in December–January and March–April 2022. In the entire observation period, 54.4% of mollusks tested positive for at least one SARS-CoV-2 target, and the rate of positive samples showed a trend similar to that of the wastewater samples. The lower SARS-CoV-2 positivity rate in bivalve mollusks compared to sewages is a direct consequence of the seawater dilution effect. Our data confirm that both sample types can be used as sentinels to detect SARS-CoV-2 in the environment and suggest their potential use in obtaining complementary information on SARS-CoV-2.

Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments.

Being overweight or obese can predispose people to chronic diseases and metabolic disorders such as cardiovascular illnesses, diabetes, Alzheimer’s disease, and cancer, which are costly public health problems and leading causes of mortality worldwide. Many people hope to solve this problem by using food supplements, as they can be self-prescribed, contain molecules of natural origin considered to be incapable of causing damage to health, and the only sacrifice they require is economic. The market offers supplements containing food plant-derived molecules (e.g., primary and secondary metabolites, vitamins, and fibers), microbes (probiotics), and microbial-derived fractions (postbiotics). They can control lipid and carbohydrate metabolism, reduce appetite (interacting with the central nervous system) and adipogenesis, influence intestinal microbiota activity, and increase energy expenditure. Unfortunately, the copious choice of products and different legislation on food supplements worldwide can confuse consumers. This review summarizes the activity and toxicity of dietary supplements for weight control to clarify their potentiality and adverse reactions. A lack of research regarding commercially available supplements has been noted. Supplements containing postbiotic moieties are of particular interest. They are easier to store and transport and are safe even for people with a deficient immune system.

Fermentable sugar dosage helps oenologists to establish a harvest’s moment and control the fermentation process of the musts. The official analyses recommended for their determination are long, laborious, and must be carried out by specialized personnel. On the contrary, instrumental analysis automation limits human errors, increases precision, and reduces the time and cost of the analyses. In the food production sector, to use methods other than those recommended by supranational bodies in official reports, it is necessary to validate the analytical processes to establish the conformity of the results between the new methods and the reference ones. This work validated an automated enzymatic apparatus to determine the sum of glucose and fructose levels in wine samples. The validation was carried out on wine samples (dry red wine, dry white wine, moderately sweet wine, and sweet wine) containing different sugar concentrations by comparing data obtained using the OIV-MA-AS311-02 method performed by a specialized operator (reference method) and the same method performed by an automated apparatus. The difference between the results’ means obtained with the two procedures was significant. Nevertheless, the automated procedure was considered suitable for the intended use since the differences between the averages were lower than the measurement uncertainty at the same concentration, and the repeatability results were better for the automated procedure than the reference method.

Environmental pollution, particularly in the marine environment, has become a significant concern due to the increasing presence of pollutants and their adverse effects on ecosystems and human health. This study focuses on the bioaccumulation of trace elements in the muscle tissue of the blackmouth catshark (Galeus melastomus) from different areas in the Mediterranean Sea. Trace elements are of interest due to their persistence, toxicity, and potential for bioaccumulation. This research aims to assess the distribution and accumulation of trace elements in the muscle tissue of G. melastomus and investigate their potential impact on the deep-sea environment of the Mediterranean. The focused areas include the Ligurian Sea, the northern and central Tyrrhenian Sea, the southern Tyrrhenian Sea, the Ionian Sea, the Pantelleria Waters, and the Gela Waters. Samples were collected following established protocols, and trace element analysis was conducted using inductively coupled plasma mass spectrometry. The study provides data on the concentrations of 17 trace elements, namely aluminum, arsenic, cadmium, cobalt, copper, manganese, molybdenum, nickel, zinc, selenium, strontium, lead, chromium, iron, barium, bismuth, and uranium. The findings contribute to a better understanding of trace element bioaccumulation patterns in elasmobranch species, specifically G. melastomus, and highlight the potential risks associated with chemical contamination in the Mediterranean Sea. This research emphasizes the importance of studying the impacts of pollutants on marine organisms, particularly those occupying key ecological roles, like sharks, to support effective conservation and management strategies.

BackgroundArterial hypertension, especially when coexisting with other cardiovascular risk factors, could determine an imbalance between myocardial energetic demand and altered efficiency, leading to an early left ventricular (LV) systolic dysfunction, even in terms of echo-derived mechano-energetic efficiency indexed for myocardial mass (MEEi). We aim to analyse an improvement in LV MEEi, if any, in a population of hypertensive patients with a long-term follow-up and to identify clinical, metabolic and therapeutic determinants of LV MEEi amelioration.Materials and methodsIn total, 7,052 hypertensive patients, followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, underwent echocardiographic and clinical evaluation. LV MEEi was obtained as the ratio between stroke volume and heart rate and normalized per grams of LV mass and ΔMEEi was calculated as difference between follow-up and baseline MEEi. Patients in the highest ΔMEEi quartile (≥0.0454 mL/s/g) (group 1) were compared to the merged first, second and third quartiles (

Between 2007 and 2022, 112 specimens of newborn and young pelagic sharks were recorded in the waters of Tuscany Region, in the South Ligurian–North Tyrrhenian Seas (north-western Mediterranean basin). The sharks belonged to the Carcharhinus plumbeus (n = 14), Prionace glauca (n = 66), Isurus oxyrinchus (n = 16), Mobula mobular (n = 5) Alopias vulpinus (n = 7) and Hexanchus griseus (n = 4) species. Each animal was correctly identified thanks to the photographs or videos collected. All specimens were incidentally captured with set nets in inshore shallow waters, except bluntnose six-gill sharks, which were bycatch of deep-water bottom-trawl fishery. Body mass, sex, total length and biometric measurements were recorded in 34 baby sharks following the Mediterranean Large Elasmobranches Monitoring (MEDLEM) protocol. The presence of very evident and often non-healed umbilical scar confirmed that some of the sample specimens were newborn. Further confirmation came from the comparison between the total length observed and the size at birth known for the sampled species as reported in the literature. Some baby sharks were preserved in the Museums of Natural History of Pisa and Florence University collections. The importance of the coastal area studied as a possible shark nursery is discussed.

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5–22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study’s primary end-point was the change from baseline in peak VO2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.