Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.     

Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.     

Gas Sensing of NiO‐SCCNT Core–Shell Heterostructures: Optimization by Radial Modulation of the Hole‐Accumulation Layer

Hierarchical core–shell (C–S) heterostructures composed of a NiO shell deposited onto stacked‐cup carbon nanotubes (SCCNTs) are synthesized by atomic layer deposition (ALD). A film of NiO particles (0.80–21.8 nm in thickness) is uniformly deposited onto the inner and outer walls of the SCCNTs. The electrical resistance of the samples is found to increase of many orders of magnitude with the increasing of the NiO thickness. The response of NiO–SCCNT sensors toward low concentrations of acetone and ethanol at 200 °C is studied. The sensing mechanism is based on the modulation of the hole‐accumulation region in the NiO shell layer upon chemisorption of the reducing gas molecules. The electrical conduction mechanism is further studied by the incorporation of an Al₂O₃ dielectric layer at NiO and SCCNT interfaces. The investigations on NiO–Al₂O₃–SCCNT, Al₂O₃–SCCNT, and NiO–SCCNT coaxial heterostructures reveal that the sensing mechanism is strictly related to the NiO shell layer. The remarkable performance of the NiO–SCCNT sensors toward acetone and ethanol benefits from the conformal coating by ALD, large surface area of the SCCNTs, and the optimized p‐NiO shell layer thickness followed by the radial modulation of the space‐charge region.     

Fibrosis of Peritoneal Membrane as Target of New Therapies in Peritoneal Dialysis

Peritoneal dialysis (PD) is an efficient renal replacement therapy for patients with end-stage renal disease. Even if it ensures an outcome equivalent to hemodialysis and a better quality of life, in the long-term, PD is associated with the development of peritoneal fibrosis and the consequents patient morbidity and PD technique failure. This unfavorable effect is mostly due to the bio-incompatibility of PD solution (mainly based on high glucose concentration). In the present review, we described the mechanisms and the signaling pathway that governs peritoneal fibrosis, epithelial to mesenchymal transition of mesothelial cells, and angiogenesis. Lastly, we summarize the present and future strategies for developing more biocompatible PD solutions.     

The Role of NLRP3 Inflammasome Activation and Oxidative Stress in Varicocele-Mediated Male Hypofertility

Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

A real time FFT-based impedance meter with bias compensation

A real time FFT-based impedance meter is here presented. It is realized simply by a standard PC in addition to a low cost two channels hardware device, and is based on a cost-effective algorithm to meaningfully reduce the known problem of the bias introduced by the relative phase and amplitude error between channels. The impedance meter exploits the implementation of an ad hoc cost-effective algorithm and a synchronous sampling allows eliminating the leakage error. The aliasing and the spectral interference are eliminated by means of an anti-aliasing filter and the use of very low distortion sinusoidal signals. Automatic measurements can be managed too, capturing different measures at different test frequencies and displaying them graphically on the PC screen. To validate the measured results comparative test were performed with respect to certified and calibrated commercially available multimeters known with good accuracies.Finally, this novel impedance meter integrates a home-made software, previously reported [1] capable to implement real time virtual instruments.     

Measurement involving human perception and interpretation

The measurement of features related to human perception and interpretation is discussed. After a brief review of the historical framework, the state of the art is presented on the basis of the authors’ experience in the field and their participation in related European projects, with development of experiments, and co-ordination activities. Future research needs and challenges are then addressed.     

The relationship between scientists’ research performance and the degree of internationalization of their research

Policy makers, at various levels of governance, generally encourage the development of research collaboration. However the underlying determinants of collaboration are not completely clear. In particular, the literature lacks studies that, taking the individual researcher as the unit of analysis, attempt to understand if and to what extent the researcher’s scientific performance might impact on his/her degree of collaboration with foreign colleagues. The current work examines the international collaborations of Italian university researchers for the period 2001–2005, and puts them in relation to each individual’s research performance. The results of the investigation, which assumes co-authorship as proxy of research collaboration, show that both research productivity and average quality of output have positive effects on the degree of international collaboration achieved by a scientist.     

Disturbed Exploitation compact Differential Evolution for limited memory optimization problems

This paper proposes a novel and unconventional Memetic Computing approach for solving continuous optimization problems characterized by memory limitations. The proposed algorithm, unlike employing an explorative evolutionary framework and a set of local search algorithms, employs multiple exploitative search within the main framework and performs a multiple step global search by means of a randomized perturbation of the virtual population corresponding to a periodical randomization of the search for the exploitative operators. The proposed Memetic Computing approach is based on a populationless (compact) evolutionary framework which, instead of processing a population of solutions, handles its statistical model. This evolutionary framework is based on a Differential Evolution which cooperatively employs two exploitative search operators: the first is based on a standard Differential Evolution mutation and exponential crossover, and the second is the trigonometric mutation. These two search operators have an exploitative action on the algorithmic framework and thus contribute to the rapid convergence of the virtual population towards promising candidate solutions. The action of these search operators is counterbalanced by a periodical stochastic perturbation of the virtual population, which has the role of “disturbing” the excessively exploitative action of the framework and thus inhibits its premature convergence. The proposed algorithm, namely Disturbed Exploitation compact Differential Evolution, is a simple and memory-wise cheap structure that makes use of the Memetic Computing paradigm in order to solve complex optimization problems. The proposed approach has been tested on a set of various test problems and compared with state-of-the-art compact algorithms and with some modern population based meta-heuristics. Numerical results show that Disturbed Exploitation compact Differential Evolution significantly outperforms all the other compact algorithms present in literature and reaches a competitive performance with respect to modern population algorithms, including some memetic approaches and complex modern Differential Evolution based algorithms. In order to show the potential of the proposed approach in real-world applications, Disturbed Exploitation compact Differential Evolution has been implemented for performing the control of a space robot by simulating the implementation within the robot micro-controller. Numerical results show the superiority of the proposed algorithm with respect to other modern compact algorithms present in literature.