The Activation Status of the TGF-β Transducer Smad2 is Associated with a Reduced Survival in Gastrointestinal Cancers: a Systematic Review and Meta-Analysis

Aberrant function of Smad2, a crucial member of the transforming growth factor beta (TGF-β) signalling, is associated with the development of malignancies, particularly in the gastrointestinal district. However, little is known about its possible prognostic role in such tumor types. With the first meta-analysis on this topic, we demonstrated that the lack of the activated form of Smad2 (phosphor-Smad2 or pSmad2), which meant to be the C-terminally phosphorylated form, showed a statistically significant association with an increased risk of all-cause mortality in patients with gastrointestinal cancers (RR, 1.58; 95% CI, 1.05–2.37, p = 0.029, I2 = 84%), also after having adjusted for potential confounders (RR, 1.65; 95% CI, 1.24–2.18; p < 0.001; I2 = 4%). This finding highlights the importance of the TGF-β signaling in this type of cancers. In this line, further studies are needed to explore more in depth this important molecular pathway, focusing also on potential therapeutic strategies based on its effectors or molecular targets

Modelling Large, Dynamic, and Heterogeneous Populations Using DNA Libraries

AbstractThe study of any population of large size and high diversity is limited by the lack of data and associated insights. For a pool of individuals, each associated with a unique characteristic feature, as the pool size grows, the possible interactions increase exponentially, quickly beyond the scope of computation, not to mention experimental manipulation and analysis. Herein, we report a facile RT-PCR-based method, to correlate the amplification curves with various DNA libraries of defined diversity, and perform operations with groups of quaternary numbers as input and diversity as output. An attractive feature of this approach is the possibility of realizing parallel computation with an eventually unlimited number of variables. We demonstrate that DNA libraries can be used to model heterogeneous populations, exhibiting functions such as self-protection, subjected to biased expansion, and to evolve into complex structures. Moreover, the method can be applied to drug discovery using DNA-encoded chemical library (DECL) technology, to optimize selection conditions for identifying potent and specific bio-molecular interactions.</jats:p

Winner(s)-take-all: nonlinear amplification of DNA-encoded library

AbstractInformation processing functions are essential for biological organisms to perceive and react to their complex enviornment, as well as for human to analyze and rationalize them. While our brain has an extraordinary power to process complex information, winner(s)-take-all computation is one of the simplest models of lateral inhibition and competition among biological neurons. It has been implemented as DNA-based neural networks, for example, to mimic pattern recognition. However, the utility of DNA-based computation in information processing for real biotechnological applications remains to be demonstrated. In this paper, we developed a winner(s)-take-all method for non-linear amplification of mixtures of DNA sequences. Unlike conventional biological experiments, selected species were not directly subjected to analysis. Instead, parallel computation among myriad of different DNA sequences was carried out with a neural network-inspired winner-take-all function, to reduce the information complexity. The method could be used for various oligonucleotide-encoded libraries, as we have demonstrated its application in decoding and data analysis for selection experiment with DNA-encoded chemical library against protein target.</jats:p

Protective Effect of Extra Virgin Olive Oil on Cancers, Gastrointestinal Cancers, and All-Cause Mortality: A Competing Risk Analysis in a Southern Italian Cohort

Background/Objectives: This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. Methods: In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005&ndash;2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: &lt;30 g/day, 30&ndash;50 g/day, and &gt;50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Results: Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30&ndash;50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63&ndash;0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65&ndash;0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21&ndash;0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31&ndash;0.81). Conclusions: The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO&rsquo;s potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet&rsquo;s overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms