Satellite cells (SC) are the stem cells of skeletal muscles. They are quiescent in adult animals but resume proliferation to allow muscle hypertrophy or regeneration after injury. The mechanisms ...balancing quiescence, self-renewal, and differentiation of SC are difficult to analyze in vivo owing to their complexity and in vitro because the staminal character of SC is lost when they are removed from the niche and is not adequately reproduced in the culture models currently available. To overcome these difficulties, we set up a culture model of the myogenic C2C12 cell line in suspension. When C2C12 cells are cultured in suspension, they enter a state of quiescence and form three-dimensional aggregates (myospheres) that produce the extracellular matrix and express markers of quiescent SC. In the initial phase of culture, a portion of the cells fuses in syncytia and abandons the myospheres. The remaining cells are mononucleated and quiescent but resume proliferation and differentiation when plated in a monolayer. The notch pathway controls the quiescent state of the cells as shown by the fact that its inhibition leads to the resumption of differentiation. Within this context, notch3 appears to play a central role in the activity of this pathway since the expression of notch1 declines soon after aggregation. In summary, the culture model of C2C12 in suspension may be used to study the cellular interactions of muscle stem cells and the pathways controlling SC quiescence entrance and maintenance.
The ideal level of ligation of the inferior mesenteric artery (IMA) during resection for colorectal cancer is still controversial. The aim of this study was to demonstrate the real advantages and, ...above all, the adequacy of oncological staging after a low ligation of the IMA with additional LN retrieval in patients undergoing surgery for colorectal cancer.
Between January 2013 and December 2020, 157 patients who underwent curative resection of a primary colorectal tumor were retrospectively included: 64 patients underwent high ligation of the IMA and 93 patients underwent low ligation of the IMA with additional LN retrieval. Results - Mean number of lymphnodes harvested (the median number of harvested nodes was 16.2 in "high ligation" group vs 15.4 in "low ligation" group), operation time (272 minutes vs 293 minutes), intraoperative blood loss (40 cc vs 53 cc) and recovery time (median postoperative hospitalization was 6.4 days in both groups) were not significantly different between the groups.
High ligation of the IMA preserves an adequate length of the colon to perform a successful anastomosis and facilitates apical LN dissection. However, it may be associated with an increased risk of anastomotic leakage. Low ligation of the IMA is less invasive and it is associated with a better preservation of genitourinary function and, futhermore, with an accurate oncological clearance.
Low ligation of the IMA with additional LN retrieval might be an oncologically safe and less invasive procedure in the surgical management of patients with colorectal cancer.
Colorectal cancer, Inferior mesenteric artery, Ligation.
Abstract Background Wild type RAS ( RAS -wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We ...examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS -wt/ BRAF- mutant ( BRAF -mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS -wt/ BRAF -mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS -wt /BRAF -mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF -mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67–1.14; p = 0.33), OS (HR, 0.91; 95% CI, 0.62–1.34; p = 0.63) and ORR (relative risk, 1.31; 95% CI 0.83–2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS -wt/ BRAF -mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.
Abstract
Animals living on small islands are more drastically exposed to environmental changes, such as food or water starvation, and rapid temperature shifts. Facing such conditions, and probably ...thank to adaptive plasticity mechanisms, some animals display a Reversed Island Syndrome (RIS), a suite of traits, including skin pigmentation, voracity, sexual dimorphism, showed differently from mainland relatives. Here, we analyse a so far poorly explored aspect of RIS: the effect of this on the microbiota composition of host Italian wall lizard (
Podarcis siculus
), strongly influenced by the animal’s lifestyle, and conditioning the same. We compare mainland and island populations, assessing the difference between their microbial communities and their response under unexpected food, experimentally provided. Our observations showed a significant difference in microbiota communities between island and mainland groups, depended mainly from changes in relative abundance of the shared genera (difference due to decrease/increase). Exposure to experimental diet regimes resulted into significative reshaping of bacterial composition of microbiota and a greater variation in body mass only in the island population. Our results could be an evidence that gut microbial community contributes to adaptive plasticity mechanisms of island lizards under RIS to efficiently respond to unexpected changes.
Stromboli (Italy) is a basaltic volcano characterized by persistent, mild strombolian activity, occasionally interrupted by lava effusion and more violent explosive events, named major explosions and ...paroxysms depending on their intensity and magnitude. The normal activity is fed by a shallow and degassed highly porphyritic (HP) shoshonitic basalt carrying about 50 vol.% crystals settled in a shoshonitic glassy matrix (K
2
O > 3.8 wt.%). The more energetic explosions erupt a deep, volatile-rich, low-porphyritic (LP) magma with < 10 vol.% crystals in a shoshonitic basaltic glassy matrix (K
2
O < 2.4 wt.%). Products with intermediate glass composition are also found in the more violent explosive events. In this study, we present a new data set of major and trace element contents in matrix glasses and minerals performed in products from different types of explosive activity that occurred at Stromboli between 1998 and 2020. This large data set is used to put constraints on the evolution and architecture of the intermediate plumbing system, where the transformation from LP to HP occurs. Results indicate that, compared to paroxysms, the glassy matrices of the LP pumices from major explosions are richer in incompatible trace elements (and K
2
O wt.%) due to < 15 wt.% fractionation of clinopyroxene and olivine. This points to a chemical zoning of the deep reservoir and suggests that major explosions are fed by magmas residing in its upper part. Among the major explosions, the homogeneous intermediate glasses in the products from the 19 July 2020 event originate from the interplay of mixing and crystal fractionation processes. The crystallization of euhedral microphenocrysts of An-rich plagioclase suggests that batches of magma can pond and crystallize for few days (< 11) at the base of the intermediate zone of the plumbing system, at pressure coinciding with the entering of plagioclase into the system (< 100 MPa). As a relevant point for understanding the pre- and syn-eruptive magma dynamics, data indicate a positive correlation between the magnitude of the explosions and the depth of the supply magma.
Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models ...recapitulating human hepatocellular carcinoma (HCC) are then used to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the resistant‐hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin‐19, indicating that several HCC‐associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene‐target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the nuclear factor erythroid related factor 2 (NRF2) pathway and up‐regulation of the miR‐200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR‐200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3‐induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin‐19‐positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated with human HCC as well underlines the translational value of our results. Conclusion: This study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target. (Hepatology 2014;58:228–241)
The Italian hare (Lepus corsicanus) is endemic to Central-Southern Italy and Sicily, classified as vulnerable due to habitat alterations, low density and fragmented populations and ecological ...competition with the sympatric European hare (Lepus europaeus). Despite this status, only few and local studies have explored its ecological features. We provided some key traits of the ecological niche of the Italian hare as well as its potential distribution in the Italian peninsula. All data derived from genetically validated presences. We generated a habitat suitability model using maximum entropy distribution model for the Italian hare and its main competitor, the European hare. The dietary habits were obtained for the Italian hare with DNA metabarcoding and High-Throughput Sequencing on faecal pellets. The most relevant environmental variables affecting the potential distribution of the Italian hare are shared with the European hare, suggesting a potential competition. The variation in the observed altitudinal distribution is statistically significant between the two species.The diet of the Italian hare all year around includes 344 plant taxa accounted by 62 families. The Fagaceae, Fabaceae, Poaceae, Rosaceae and Solanaceae (counts > 20,000) represented the 90.22% of the total diet. Fabaceae (60.70%) and Fagaceae (67.47%) were the most abundant plant items occurring in the Spring/Summer and Autumn/Winter diets, respectively. The Spring/Summer diet showed richness (N = 266) and diversity index values (Shannon: 2.329, Evenness: 0.03858, Equitability: 0.4169) higher than the Autumn/Winter diet (N = 199, Shannon: 1.818, Evenness: 0.03096, Equitability: 0.3435). Our contribution adds important information to broaden the knowledge on the environmental (spatial and trophic) requirements of the Italian hare, representing effective support for fitting management actions in conservation planning.
To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax ...(previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit-risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories.
The Eurasian otter (
) underwent a strong decline in large areas of the Central-Western part of its distribution range, during the second half of the twentieth century. In Italy, only residual ...fragmented nuclei survive in the Central-Southern part of the peninsula. Nowadays, the otter is one of the most endangered mammals in Italy, and increasing the knowledge about the ecology of this species is a key step in defining fitting management strategies. Here we provide information about the diet of otter on the Agri river system, one of the most important presence sites in Italy, to understand both the species' food requirements and the impact on fish communities.
DNA metabarcoding and High Throughput Sequencing were used on DNA extracted from spraints. We amplified DNA with a primer set for vertebrates, focusing efforts on the bulk of the otter's diet (fishes and amphibians).
Our findings showed that the diet of the otter was dominated by cyprinids (97.77%, and 99.14% of fishes), while amphibians represented 0.85% of the sequences analyzed. Results are in general accordance with previous studies based on morphological characterization; however, molecular analyses allow the resolving of some morphological uncertainties. Although the study area offers a very wide range of available prey, the diet of the otters shows marked selectivity. We highlighted a variation in prey consumed, in accordance with the typology of water system (i.e., river, lake, tributary). Some of the preys found in the diet were alien species introduced by man for sport fishing. Our findings could help define strategies useful for the conservation of the otter population in Southern Italy, suggesting management actions directed at avoiding fish community alterations through illegal stockings without severe controls on their taxonomic status. These introductions could result in a general reduction in the diversity of the otter's preys, affecting its predatory behavior.
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