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Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal–lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic–ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 ( Ambra1 +/gt ) . Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.

Jingmen tick virus (JMTV) is a novel flavi-like virus first identified in 2010 in Rhipicephalus microplus in the Jingmen region of Hubei Province, China and has been reported in different Asian countries, Central and South America, Africa, and Europe. Beyond ticks, JMTV has been detected in a range of other arthropods and in vertebrate hosts. In humans, JMTV has been found in patients with Crimean-Congo hemorrhagic fever in Kosovo and Turkey, and in febrile patients with a history of tick bites in China, suggesting it may be a novel human pathogen. To investigate the presence of JMTV in Italy, we developed a One-step real-time RT-PCR assay and applied it to individually screen 1150 ticks collected from northeastern, central, and southern Italy. JMTV RNA was detected in multiple tick species, including Ixodes ricinus, Rhipicephalus bursa, Rhipicephalus sanguineus s.l., Dermacentor marginatus, and Hyalomma marginatum with a prevalence ranging from 0.52% to 18.42% in questing ticks. The detection of JMTV in ticks from all surveyed areas, indicates that the virus is geographically widespread in Italy. These findings highlight the need for comprehensive surveillance strategies to identify new areas of active virus circulation and to investigate the potential impact of JMTV on public health.

Monitoring stranded cetaceans represents a strategic method to assess their health, conservation status, and ecological role in the marine ecosystem. Efficient stranding networks and standardized protocols are essential to monitor this phenomenon and investigate its causes. This study assesses the evidence of fishery interaction on stranded cetacean carcasses found along the Italian coastline from 1986 to 2023. Evidence assessment and post-mortem investigation methods evolved over three macro-periods, from non-standardized reporting (1986–2014) to an integrated national stranding network (2015–2019), and finally to the creation of a new standardized, evidence-based diagnostic framework under the EU-funded LIFE DELFI project (LIFE18 NAT/IT/000942) (2020–2023). A total of 5355 cases were selected for this analysis. A literature review and evidence of interaction on stranded carcasses supported the categorization of findings, ranging from case history to pathological observations, allowing the assessment of temporal variation, demographic parameters, geographical distribution, and fishing gear identification. Evidence of fishery interaction was found in 12.89% of the cases (690/5355), with an annual average of 18.15 affected animals, and fishery interaction was identified as the likely cause of death in 10.32% of the cases. The most frequently reported species were Stenella coeruleoalba and Tursiops truncatus , showing significant differences in fishery interactions, particularly in relation to sex, age class, and geographical distribution. Adult male Tursiops truncatus exhibited a higher susceptibility to gillnet interaction in the Adriatic Sea. The results of this study emphasize the importance of standardized post-mortem investigations and long-term monitoring to identify risk hotspots, implement species- and region-specific mitigation strategies, and establish threshold values for cetacean conservation.

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.

Excitotoxicity has been implicated in the retinal neuronal loss in several ocular pathologies including glaucoma. Dysfunction of Excitatory Amino Acid Transporters is often a key component of the cascade leading to excitotoxic cell death. In the retina, glutamate transport is mainly operated by the glial glutamate transporter GLAST and the neuronal transporter GLT-1. In this study we evaluated the expression of GLAST and GLT-1 in a rat model of acute glaucoma based on the transient increase of intraocular pressure (IOP) and characterized by high glutamate levels during the reperfusion that follows the ischemic event associated with raised IOP. No changes were reported in GLAST expression while, at neuronal level, a reduction of glutamate uptake and of transporter reversal-mediated glutamate release was observed in isolated retinal synaptosomes. This was accompanied by modulation of GLT-1 expression leading to the reduction of the canonical 65 kDa form and upregulation of a GLT-1-related 38 kDa protein. These results support a role for neuronal transporters in glutamate accumulation observed in the retina following an ischemic event and suggest the presence of a GLT-1 neuronal new alternative splice variant, induced in response to the detrimental stimulus.

This article introduces a new web-based and freely accessible tool, the Nitrate Fate tool (NFt), for the assessment of groundwater vulnerability to nitrate pollution in a variety of pedoclimatic conditions. The contamination of water resources by nitrate, in fact, represents a growing and persistent global environmental problem, and the utilization of practical tools to assist personnel working in the agricultural sector is key for mitigating the impact on land use, while maintaining farmers’ incomes. The (NFt) has been developed and integrated into the geospatial decision support system, LandSupport, as a way to support multiple stakeholders in conducting the so-called what-if scenario analysis (e.g., what would happen to the crop production if I substitute a quote of inorganic fertilizer with the same quote of an organic one?). The tool couples a state-of-art crop-growth model—which simulates crop growth dynamics, the nitrogen and carbon cycles—with a novel transfer function model in order to assess the transport of nitrate through the unsaturated zone to the groundwater table. Within the LandSupport platform, the results are shown both as coloured maps and as cumulative charts representing the travel times and the concentrations of root leachate to groundwater table depths. This work details the tool’s rationale, the coupling of the models, and their implementation. Moreover, this article shows examples of applications supporting several public authorities and end-users, underlining that, by combining all of the information on soils, groundwater table depths, management and climates, it is possible to obtain a comprehensive understanding of nitrogen transport dynamics. Two case studies are presented: the Piana del Sele and the eastern plain of Naples, both located in the Campania region of Italy. The results of the tool’s applications reveal significant groundwater vulnerability in both plains, mainly due to the shallow groundwater table depths, resulting in remarkably fast mean nitrate travel times ranging from 0 to 6 years. Finally, the tool provides a reproducible and replicable solution, and future implementation is foreseen for additional case studies all over the world.

The anisakid nematode Sulcascaris (S.) sulcata is one of the most frequently reported pathogenic parasites of the gastrointestinal tract of sea turtles, with a wide distribution in warm marine ecosystems of the Pacific, Atlantic, and Mediterranean basins. Sea turtles, including the Mediterranean loggerhead turtle (Caretta caretta), act as definitive hosts by ingesting infected bivalve and gastropod mollusks containing fourth-stage larvae. Infected sea turtles typically develop ulcerative gastritis and chronic mucosal inflammation. We molecularly characterized 19 anisakid nematodes collected from the gastric tract of stranded C. caretta (n = 19) along the Adriatic and Ionian coasts and examined them at local Zooprophylactic Institutes. Stomach samples from five severely infested turtles were also submitted to histological analysis. Species identification was performed through two conventional PCRs targeting MT-CO1 and MT-CO2, and sequencing of 35 amplicons confirmed their identity as S. sulcata, revealing high genetic homogeneity. Phylogenetic analyses showed no clustering by geographic origin or host. Pathological examination revealed mucocatarrhal gastritis with ulcerative lesions, while histological analysis showed chronic gastritis characterized by lymphocytic infiltration. These findings refine current knowledge on S. sulcata distribution and host–parasite dynamics, with implications for marine turtle health and intermediate-host ecology.

Immunotherapy has emerged as promising treatment in sarcomas, but the high variability in terms of histology, clinical behavior and response to treatments determines a particular challenge for its role in these neoplasms. Tumor immune microenvironment (TiME) of sarcomas reflects the heterogeneity of these tumors originating from mesenchymal cells and encompassing more than 100 histologies. Advances in the understanding of the complexity of TiME have led to an improvement of the immunotherapeutic responsiveness in sarcomas, that at first showed disappointing results. The proposed immune-classification of sarcomas based on the interaction between immune cell populations and tumor cells showed to have a prognostic and potential predictive role for immunotherapies. Several studies have explored the clinical impact of immune therapies in the management of these histotypes leading to controversial results. The presence of Tumor Infiltrating Lymphocytes (TIL) seems to correlate with an improvement in the survival of patients and with a higher responsiveness to immunotherapy. In this context, it is important to consider that also immune-related genes (IRGs) have been demonstrated to have a key role in tumorigenesis and in the building of tumor immune microenvironment. The IRGs landscape in soft tissue and bone sarcomas is characterized by the connection between several tumor-related genes that can assume a potential prognostic and predictive therapeutic role. In this paper, we reviewed the state of art of the principal immune strategies in the management of sarcomas including their clinical and translational relevance.

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

Background Soft tissue sarcomas (STS) are a rare group of solid neoplasm including among others liposarcoma, leiomyosarcoma (L-sarcoma) and undifferentiated pleomorphic sarcoma (UPS) entities. The current first-line treatment is represented by anthracycline based- regimens, second-line may include trabectedin. Currently the activity of trabectedin and its mechanism of action is not completely elucidated. Methods Taking the advantages of our 3D patient-derived primary culture translational model we performed genomic-, chemobiogram, proteomic- and in vivo analysis in a UPS culture (S1). Furthermore pharmacological profiling of a UPS and L-sarcoma patient-derived case series and in silico analysis were carried out. Results Trabectedin exhibited an increased activity in 3D respect to 2D cultures suggesting an extracellular matrix (ECM) and timp1 involvement in its mechanism of action. Moreover 3D S1 xenotranspanted zebrafish model showed an increased sensitivity to trabectedin. Finally the results were further validated in a UPS and L-sarcoma case series. Conclusions Taken together these results confirmed the activity of trabectedin in these STS histotypes. Moreover the data underline the ECM involvement in the cytotoxic effect mediated by trabectedin and could open the door for researches aimed to focus on the patient setting that could benefit from this agent.