Extracellular vesicles in cardiac repair and regeneration: Beyond stem-cell-based approaches.

The adult human heart poorly regenerate after injury due to the low self-renewal capability retained by adult cardiomyocytes. In the last two decades, several clinical studies have reported the ability of stem cells to induce cardiac regeneration. However, low cell integration and survival into the tissue has limited stem-cell-based clinical approaches. More recently, the release of paracrine mediators including extracellular vesicles (EV) has been recognized as the most relevant mechanism driving benefits upon cell-based therapy. In particular, EV have emerged as key mediators of cardiac repair after damage, in terms of reduction of apoptosis, resolution of inflammation and new blood vessel formation. Herein, mechanisms involved in cardiac damage and regeneration, and current applications of EV and their small non-coding RNAs (miRNAs) in regenerative medicine are discussed

HIV-Reverse Transcriptase Inhibition: Inclusion of Ligand-Induced Fit by Cross-Docking Studies

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) have, in addition to the nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), a definitive role in the treatment of HIV-1 infections. Since the appearance of HEPT and TIBO, more than 30 structurally different classes of compounds have been reported as NNRTIs, which are specific inhibitors of HIV-1 replication, targeting the HIV-1 reverse transcriptase (RT). Nevirapine and delavirdine are the first formally licensed for clinical use, and others have been licensed afterward, while several are in preclinical or clinical development. The NNRTIs interact with a specific site of HIV-1 RT (nonnucleoside binding site, NNBS) that is close to, but distinct from, the NRTI binding site. In this work we report the application of the Autodock program assessing its usability through reproduction of 41 NNRTI experimental bound conformations. Moreover, cross-docking experiments on the wild-type and mutated RT forms were conducted to take into account the enzyme flexibility as a valuable tool for structure-based drug design (SBDD) studies and to gain insight on the mode of action of new anti-HIV agents active against both wild-type and resistant strains

Fluorescence spectroscopy of normal and follicular cancer samples from human thyroid

An autofluorescence analysis has been performed on healthy as well as tumour thyroid tissue samples to distinguish follicular cancer from normal thyroid. Complete spectra and synchronous spectra have been recordered from properly stored samples. Fluorescence bands located at 350 nm and 400 nm has been observed in the analysed cancer samples

Machine Learning Can Predict the Timing and Size of Analog Earthquakes

Despite the growing spatiotemporal density of geophysical observations at subduction zones, predicting the timing and size of future earthquakes remains a challenge. Here we simulate multiple seismic cycles in a laboratory‐scale subduction zone. The model creates both partial and full margin ruptures, simulating magnitude M_w 6.2–8.3 earthquakes with a coefficient of variation in recurrence intervals of 0.5, similar to real subduction zones. We show that the common procedure of estimating the next earthquake size from slip‐deficit is unreliable. On the contrary, machine learning predicts well the timing and size of laboratory earthquakes by reconstructing and properly interpreting the spatiotemporally complex loading history of the system. These results promise substantial progress in real earthquake forecasting, as they suggest that the complex motion recorded by geodesists at subduction zones might be diagnostic of earthquake imminence