CXCL12/SDF-1 from perisynaptic Schwann cells promotes regeneration of injured motor axonterminals

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter-cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12, also abbreviated as stromal-derived factor-1 (SDF-1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by -latrotoxin. CXCL12 acts via binding to the neuronal CXCR4 receptor. A CXCL12-neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration invivo. Recombinant CXCL12 invivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons invitro. These findings indicate that the CXCL12-CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage

Virus contamination and infectivity in beach environment: Focus on sand and stranded material

To assess the exposure of beachgoers to viruses, a study on seawater, sand, and beach-stranded material was carried out, searching for human viruses, fecal indicator organisms, and total fungi. Moreover, for the first time, the genome persistence and infectivity of two model viruses was studied in laboratory-spiked sand and seawater samples during a one-week experiment. Viral genome was detected in 13.6 % of the environmental samples, but it was not infectious (Human Adenovirus – HAdV, and enterovirus). Norovirus and SARS-CoV-2 were not detected. The most contaminated samples were from sand and close to riverine discharges. In lab-scale experiments, the infectivity of HAdV5 decreased by ~1.5-Log10 in a week, the one of Human Coronavirus-229E disappeared in <3 h in sand. The genome of both viruses persisted throughout the experiment. Our results confirm viral contamination of the beach and suggest HAdV as an index pathogen for beach monitoring and quantitative risk assessment

Hepatitis C Virus Infection and Human Pancreatic β-Cell Dysfunction

n/

CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by α‐latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α‐neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo. Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro. These findings indicate that the CXCL12α‐CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury. The present results have important implications in the effort to find therapeutics and protocols to improve recovery of function after different forms of motor axon terminal damage

Cancer astrocytes have a more conserved molecular status in long recurrence free survival (RFS) IDH1 wild-type glioblastoma patients: New emerging cancer players

Glioblastoma is a devastating disease that despite all the information gathered so far, its optimal management remains elusive due to the absence of validated targets from clinical studies. A better clarification of the molecular mechanisms is needed. In this study, having access to IDH1 wild-type glioblastoma of patients with exceptionally long recurrence free survival (RFS), we decided to compare their mutational and gene expression profile to groups of IDH1 wild-type glioblastoma of patients with shorter RFS, by using NGS technology. The exome analysis revealed that Long-RFS tumors have a lower mutational rate compared to the other groups. A total of 158 genes were found differentially expressed among the groups, 112 of which distinguished the two RFS extreme groups. Overall, the exome data suggests that shorter RFS tumors could be, chronologically, in a more advanced state in the muli-step tumor process of sequential accumulation of mutations. New players in this kind of cancer emerge from the analysis, confirmed at the RNA/DNA level, identifying, therefore, possible oncodrivers or tumor suppressor genes

ANKRd44 gene silencing: a putative role in trastuzumab resistance in HER2-like breast cancer

Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance

I want to be safe: understanding the main drivers behind vaccination choice throughout the pandemic

Abstract Background Despite being a major advancement in modern medicine, vaccines face widespread hesitancy and refusal, posing challenges to immunization campaigns. The COVID-19 pandemic accentuated vaccine hesitancy, emphasizing the pivotal role of beliefs in efficacy and safety on vaccine acceptance rates. This study explores the influence of efficacy and safety perceptions on vaccine uptake in Italy during the pandemic. Methods We administered a 70-item questionnaire to a representative sample of 600 Italian speakers. Participants were tasked with assessing the perceived effectiveness and safety of each vaccine dose, along with providing reasons influencing their vaccination choices. Additionally, we conducted an experimental manipulation, exploring the effects of four framing messages that emphasized safety and/or efficacy on participants’ willingness to receive a hypothetical fourth vaccine dose. Furthermore, participants were asked about their level of trust in the scientific community and public authorities, as well as their use of different information channels for obtaining COVID-19-related information. Results Our study reveals a dynamic shift in vaccine efficacy and safety perceptions throughout the COVID-19 pandemic, potentially influencing vaccination compliance. Initially perceived as more effective than safe, this assessment reversed by the time of the third dose. Beliefs regarding safety, rather than efficacy, played a significant role in anticipating future vaccinations (e.g., the booster dose). Safety-focused messages positively affected vaccination intent, while efficacy-focused messages showed limited impact. We also observed a changing trend in reasons for vaccination, with a decline in infection-related reasons and an increase in social related ones. Furthermore, trust dynamics evolved differently for public authorities and the scientific community. Conclusions Vaccine perception is a dynamic process shaped by evolving factors like efficacy and safety perceptions, trust levels, and individual motivations. Our study sheds light on the complex dynamics that underlie the perception of vaccine safety and efficacy, and their impact on willingness to vaccinate. We discuss these results in light of bounded rationality, loss aversion and classic utility theory

Tumor growth-arrest effect of tetrahydroquinazoline-derivative human topoisomerase II-alpha inhibitor in HPV-negative head and neck squamous cell carcinoma

Abstract Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. There is a persisting demand for new approaches to establish more efficient strategies for their treatment. In this regard, the human topoisomerase II (topoII) enzyme is a validated chemotherapeutics target, as topoII regulates vital cellular processes such as DNA replication, transcription, recombination, and chromosome segregation in cells. TopoII inhibitors are currently used to treat some neoplasms such as breast and small cells lung carcinomas. Additionally, topoII inhibitors are under investigation for the treatment of other cancer types, including oral cancer. Here, we report the therapeutic effect of a tetrahydroquinazoline derivative (named ARN21934) that preferentially inhibits the alpha isoform of human topoII. The treatment efficacy of ARN21934 has been evaluated in 2D cell cultures, 3D in vitro systems, and in chick chorioallantoic membrane cancer models. Overall, this work paves the way for further preclinical developments of ARN21934 and possibly other topoII alpha inhibitors of this promising chemical class as a new chemotherapeutic approach for the treatment of oral neoplasms

Beach pollution from marine litter: Analysis with the DPSIR framework (driver, pressure, state, impact, response) in Tuscany, Italy

Beaches are affected by the accumulation of natural and anthropogenic material; however, this environmental issue has not yet been explored from a One Health perspective. In this paper, the conceptual framework of DPSIR (Drivers-Pressures-State-Impact-Response) was used to understand the beach-stranded material issue in a systemic way and a data-based classification for some environmental indicators was developed to support the DPSIR analysis. The model was applied to an Italian coastal municipality as a case study, through the collection of data from a variety of data sources: publicly accessible database, data from a stakeholders’ network (i.e., coastal authority, solid waste company, sewerage company, drainage consortium), and fieldwork consisting in microbiological analysis of stranded material and underlying sand, visual census of macrolitter along beach and waterways. In the study area, solid wastes production was a high pressure (768 kg/capita/year), but in situ visual observations of floating wastes at the outlet of the canals revealed that the contribution of local waterways to marine litter was negligible, thus suggesting the effectiveness of the measures adopted along local waterways by the drainage consortium (i.e., grids at the drainage pumping stations). Nevertheless, very high quantity of anthropogenic wastes was counted during the beach litter surveys (603 items/100 m), probably as a result of coastal current pathway that transported material from major watercourses (>100 km2 drainage basin size; 23 items/h). On the contrary, local sewage production represented a very high pressure (>33,000 m3/km) that impacted on the microbiological quality of the stranded material with moderate to high level of fecal bacteria indicators detected in the beach cast. The underlying sand was affected by such contamination, with most of the sample within the provisional limit set by WHO for enterococci in beach sand (60 CFU/g) that was associated to a health risk of<5 % of gastroenteritis attributable to accidental ingestion of sand; nevertheless, some enterococci peak values (980 MPN/g) could be associated to a health risk for gastroenteritis>10 %. The beach-stranded material was collected without separating the sand, with annual quantity of 1,243 kg/m, that was processed in a dedicated facility allowing to recover up to 98 % of sand and biomass after the treatment, with moderate expenditure for the coastal municipality (22 €/m). Overall, this study allowed to better figure out the cause-effect relationships underlying the accumulation of stranded material along shoreline and the effectiveness of the management practices toward beach-stranded material. Therefore, the usage of the DPSIR framework as structuring model to understand the problem of stranded material could be useful for beach managers and administrators, and its adoption within beach management programs is worth for improving beach quality