Estimations of length-weight relationships and consumption rates of odontocetes in the Mediterranean Sea from stranding data

Stranding data provide fundamental information on biometric traits of cetaceans useful to increase knowledge on ecological traits and their consumption patterns. In this study, the length weight (L-W) relationships through the power regression model (W = a ×Lb ) were calculated for three dolphin species (the striped dolphin, the common bottlenose dolphin and the Risso’s dolphin) in several Mediterranean subregions and at the scale of the entire basin. Length (L) and weight (W) data were collected from stranding records during the period from 1983 to 2021 acquired from several databases and the literature. Starting from L-W relationships, a bootstrap method was applied to estimate the mean body weights, the daily ingested biomass (IB) and annual food consumption (AFC) rates of different dolphin species. In particular, four different equations were used to estimate the IB rates. Prey consumption by dolphin species was calculated through AFC rates and the available diet information (expressed in weight fractions) of dolphin species for different Mediterranean subregions. Considering the L-W relationships in the Mediterranean Sea, b coefficient values were equal to 2.578, 2.975 and 2.988 for the striped, the common bottlenose and the Risso’s dolphin, respectively. At the Mediterranean scale, the AFC values estimated were 3913 kg (CI 2469–5306) for the Risso’s dolphin, 2571 kg (1372–3963) for the common bottlenose dolphin and 1118 kg (531–1570) for the striped dolphin. Prey consumption pattern showed a clear partitioning among the investigated species, where the common bottlenose dolphin exploits neritic demersal and pelagic fishes (e.g. eel fishes, sparids), the striped dolphin exploits mesopelagic fishes and myctophids, and the Risso’s dolphin was specialized on bathyal cephalopods of Histioteuthidae family. The results obtained in this study provide new information for the investigated species in several Mediterranean subregions providing a first consistent baseline to support the population dynamics modelling. At the same time, the wide uncertainty ranges of some parameters, as well as the lack of information for some species, stress the necessity of improving the data collection associated to stranding events, especially in the southern Mediterranean areas

Synergistic effect induced by gold nanoparticles with polyphenols shell during thermal therapy: Macrophage inflammatory response and cancer cell death assessment

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment

Application of a multi-species bio-economic modelling approach to explore fishing traits within eligible cetacean conservation areas in the Northern Ionian Sea (Central Mediterranean Sea)

The assessment of the spatial overlap between eligible cetacean conservation areas (CCAs) and fishing grounds could be a strategic element in the implementation of effective conservation measures in the pelagic offshore areas. A multi-species bio-economic modelling approach has been applied to estimate the fishing traits in eligible CCAs in the Northern Ionian Sea (NIS, Central Mediterranean Sea) between 10-800 m of depth, adopting the Spatial MAnagement of demersal Resources for Trawl fisheries model (SMART). Four possible CCAs were defined according to the distribution of cetacean species, their bio-ecological needs, as well as socio-economic needs of human activities, identifying a Blue, Red, Orange and Green CCAs in the NIS. SMART spatial domain was a grid with 500 square cells (15x15 NM). The analysis was conducted for the period 2016-2019, considering the Otter Trawl Bottom (OTB) fleet activities in the study areas through the Vessel Monitoring System. The spatial extension of fishing activities, hourly fishing effort (h), landings (tons) and economic value (euros) for each CCA and the NIS were estimated as yearly median values. Fishing activities were absent in the Blue CCA, where the presence of the submarine canyon head does not offer accessible fishing grounds. The hourly fishing effort in the Green area accounted for about 22% (3443 h) of the total hourly effort of the NIS, while the Orange and Red areas were about 8% (1226 h) and 2% (295 h), respectively. The Green CCA corresponded to about 14% (36 tons) of the total landings in the NIS, whereas the Orange and Red areas represented about 9% (22 tons) and 6% (16 tons), respectively. The Green CCA accounted for about 13% (156 thousand euros) of the total economic value of the NIS, while the Orange and Red areas represented about 6% (69 thousand euros) and 4% (44thousand euros), respectively. Results showed no or negligible negative effects on trawl activities by potential spatial restrictions due to the establishment of CCAs highlighting the importance to consider spatially integrated information during the establishment process of conservation areas for cetacean biodiversity according to the principles of Ecosystem Based Management

Addressing cetacean–fishery interactions to inform a deep-sea ecosystem-based management in the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea)

Understanding of cetaceans’ trophic role and the quantification of their impacts on the food web is a critical task, especially when data on their prey are linked to deep-sea ecosystems, which are often exposed to excessive exploitation of fishery resources due to poor management. This aspect represents one of the major issues in marine resource management, and trade-offs are needed to simultaneously support the conservation of cetaceans and their irreplaceable ecological role, together with sustainable fishing yield. In that regard, food web models can represent useful tools to support decision-making processes according to an ecosystem-based management (EBM) approach. This study provides a focus on the feeding activity occurrence and the trophic interactions between odontocetes and the fishery in the marine food web of the Gulf of Taranto (Northern Ionian Sea, Central Mediterranean Sea), by zooming in on cetaceans’ prey of commercial interest. In particular, the quantification of trophic impacts is estimated using a food web mass-balance model that integrates information on the bathymetric displacement of both cetaceans’ prey and fishing activity. The results are discussed from a management perspective to guide future research and knowledge enhancement activities as well as support the implementation of an EBM approach

Characterisation of the immune-related transcriptome in resected biliary tract cancers

Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906

Programmed cell death 4 (PDCD4) as a novel prognostic marker for papillary thyroid carcinoma

Background: The primary goal of papillary thyroid cancer (PTC) management was to stratify patients at pre- and post-surgical level to identify the small proportion of cases with potentially aggressive disease. Purpose: The aim of our study is to evaluate the possible role of programmed cell death 4 (PDCD4) and BRAF status as prognostic markers in PTC. Patients and methods: We investigate programmed cell death 4 (PDCD4) immunohistochemical expression in 125 consecutive PTCs with median follow-up of 75.3 months (range, 15\u201398 months) to verify the possible correlation between BRAF status and correlate the classical clinicopathological prognostic factors and PTC outcome with PDCD4 expression. To further support the data, miR-21 expression was tested (by quantitative real-time PCR and in situ hybridization) in a different series of 30 cases (15 PTCs BRAFwt and 15 PTCs BRAFV600E). Moreover, we validated our results using TGCA thyroid carcinoma dataset. Results: We found that 59.8% of the patients showed low-grade PDCD4 nuclear expression and low-grade expression correlated with BRAF V600E. Compared with BRAF 15 wild-type tissue samples, a significant miR-21 up-regulation was associated with BRAF V600E mutations. Lowgrade PDCD4 resulted, and was associated with aggressive histological variants, higher cancer size, extra-thyroidal extension, multifocality, lymph-node metastasis and lymph nodal ratio at the diagnosis. Concerning the outcome, the low-grade PDCD4 expression correlated at univariate and multivariate analysis, with lower levels of recurrence-free survival rate (RFS) and with poor outcome. Moreover, there was significant association between BRAF V600E patients with PDCD4 nuclear loss and lower RFS, whilet here was significant association between BRAF wild-type patients with PDCD4 nuclear expression and better outcome. Conclusion: These results showed that PDCD4 could predict PTC outcome and that the sum of PDCD4 and BRAF alterations increases the prognostic power of BRAF mutation alone

DEVELOPMENT AND VALIDATION OF A PET RADIOMICS PROGNOSTIC MODEL FOR DIFFUSE LARGE B CELL LYMPHOMA

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MIR21-induced loss of junctional adhesion molecule A promotes activation of oncogenic pathways, progression and metastasis in colorectal cancer.

Junctional adhesion molecules (JAMs) play a critical role in cell permeability, polarity and migration. JAM-A, a key protein of the JAM family, is altered in a number of conditions including cancer; however, consequences of JAM-A dysregulation on carcinogenesis appear to be tissue dependent and organ dependent with significant implications for the use of JAM-A as a biomarker or therapeutic target. Here, we test the expression and prognostic role of JAM-A downregulation in primary and metastatic colorectal cancer (CRC) (n = 947). We show that JAM-A downregulation is observed in ~60% of CRC and correlates with poor outcome in four cohorts of stages II and III CRC (n = 1098). Using JAM-A knockdown, re-expression and rescue experiments in cell line monolayers, 3D spheroids, patient-derived organoids and xenotransplants, we demonstrate that JAM-A silencing promotes proliferation and migration in 2D and 3D cell models and increases tumour volume and metastases in vivo. Using gene-expression and proteomic analyses, we show that JAM-A downregulation results in the activation of ERK, AKT and ROCK pathways and leads to decreased bone morphogenetic protein 7 expression. We identify MIR21 upregulation as the cause of JAM-A downregulation and show that JAM-A rescue mitigates the effects of MIR21 overexpression on cancer phenotype. Our results identify a novel molecular loop involving MIR21 dysregulation, JAM-A silencing and activation of multiple oncogenic pathways in promoting invasiveness and metastasis in CRC

Papillary Thyroid Carcinoma: Molecular Distinction by MicroRNA Profiling

Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription–PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted