Macrophage-Mediated Melanoma Reduction after HP-NAP Treatment in a Zebrafish Xenograft Model

The Helicobacter pylori Neutrophil Activating Protein (HP-NAP) is endowed with immunomodulatory properties that make it a potential candidate for anticancer therapeutic applications. By activating cytotoxic Th1 responses, HP-NAP inhibits the growth of bladder cancer and enhances the anti-tumor activity of oncolytic viruses in the treatment of metastatic breast cancer and neuroendocrine tumors. The possibility that HP-NAP exerts its anti-tumor effect also by modulating the activity of innate immune cells has not yet been explored. Taking advantage of the zebrafish model, we examined the therapeutic efficacy of HP-NAP against metastatic human melanoma, limiting the observational window to 9 days post-fertilization, well before the maturation of the adaptive immunity. Human melanoma cells were xenotransplanted into zebrafish embryos and tracked in the presence or absence of HP-NAP. The behavior and phenotype of macrophages and the impact of their drug-induced depletion were analyzed exploiting macrophage-expressed transgenes. HP-NAP administration efficiently inhibited tumor growth and metastasis and this was accompanied by strong recruitment of macrophages with a pro-inflammatory profile at the tumor site. The depletion of macrophages almost completely abrogated the ability of HP-NAP to counteract tumor growth. Our findings highlight the pivotal role of activated macrophages in counteracting melanoma growth and support the notion that HP-NAP might become a new biological therapeutic agent for the treatment of metastatic melanomas.     

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.     

Modeling of the dynamic mechanical properties of semicrystalline thermoplastic matrix composites

The modeling of the viscoelastic properties of semicrystalline polymeric matrix composites is discussed. Different mathematical models are applied to describe the development of the storage modulus, measured by dynamic mechanical analysis, as a function of the crystalline content during isothermal crystallization experiments. Best results are obtained with an empirical power law model developed in this work. The application of the Halpin-Tsai equation and of a theoretical model, based on a combination of parallel-series arrangements of viscoelastic elements representing the crystalline and amorphous phases, is also discussed. The main objective of this research is the comparison between experimental results obtained by differential scanning calorimetry and dynamic mechanical analysis during crystallization processes.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

有效控制板坯浇铸用的技术软件包

近年来，达涅利自动化公司在板坯连铸控制方面积累了相当多的经验。和达涅利威恩联合公司(薄板坯连铸机)及达涅利戴维狄斯汀顿(厚板坯连铸机)合作顺利完成的大量工程项目使本公司能够开发一套改善生产流程和优化浇铸过程的技术方案。这些方案是以技术软件包的形式，随硬件、软件、文件及服务一起提供的，它们可以安装在新建连铸机上或改造后的现有装置上。介绍了板坯连铸的主要技术软件包和成功应用的某些现有项目。     

Confinement-Shear Lattice Model for Concrete Damage in Tension and Compression: II. Computation and Validation

The concrete material model developed in the preceding Part I of this study is formulated numerically. The new model is then verified by comparisons with experimental data for compressive and tensile uniaxial tests, biaxial tests, and triaxial tests, as well as notched tests of mode I fracture and size effect.     

Effects of reinforcing fibers on the crystallization of polypropylene

The effects of the incorporation of different types of fibers on the crystallization kinetics and thermodynamics of isotactic polypropylene (iPP) are investigated. The study is mainly performed by thermal analysis, both in isothermal and constant cooling rate conditions, utilizing differential scanning calorimetry (DSC). The crystallization kinetics of the studied composites is successfully described by the Avrami model. Moreover, the effects of different kind of fibers are studied comparing the values of kinetics parameters such as the Avrami exponent n, the kinetic constant of the crystallization rate, Kn and the half‐time of crystallization, T 1/2. The results of the investigation show that the fibers behave as effective nucleant agents for the crystallization of polypropylene. In fact, a dramatic decrease of the half‐time of crystallization, T1/2, as well as a sensible increase of the overall crystallization rate, Kn, are observed in the presence of all the fibers analyzed. These effects are more marked in the presence of aramid fibers. The Avrami model is successfully applied to describe the crystallization kinetics of the composites. The kinetic curves obtained under non‐isothermal conditions confirm the results obtained under isothermal conditions and demonstrate the nucleating action of the fibers on the PP crystallization. Furthermore, the spherulite growth and the transcrystallinity on the surface of the fibers are investigated by optical polarizing microscopy. It is observed that transcrystallinity takes place in all kind of fibers studied, but also in this case, aramid fibers are the most effective in promoting transcrystallinity.     

Chemical characterisation of Thymus populations belonging from Southern Italy

The genus Thymus L. consists of many species of herbaceous perennials and sub-shrubs. A chemical characterisation of a collection of Thymus spp. originated from regions of Southern Italy was performed using GC and GC/MS. The accessions were collected from various natural habitats of the Basilicata and Puglia Regions and transferred into a new uniform environment. The study showed that amongst the 22 components of the oils the most recurrent ones were geraniol, thymol and α-terpinene followed by linalool, citral and trans-caryophillene. Cluster analysis led to the identification of two chemotypes: geraniol and thymol/α-terpinene; only a biotype remained separate from all others, probably because of its high content linalool (58%).     

Toxic metals (Hg, Cd, and Pb) in fishery products imported into Italy: suitability for human consumption

Mercury, cadmium, and lead concentrations were determined in various fishery products (fishes, cephalopod molluscs, and crustaceans) imported into Italy from many European and non-European coastal countries. Considerable differences were found in the concentrations of these metals among the products tested. The highest mean Hg concentration was found in fishes (0.21 μg g(-1) wet weight), whereas cephalopods had the highest mean Cd concentration (0.35 μg g(-1) wet weight). Swordfish (0.80 μg g(-1) wet weight), longtail tuna (0.53 μg g(-1) wet weight), and thornback ray (0.52 μg g(-1) wet weight) had the highest concentrations of Hg, whereas maximum Cd concentrations were found in samples of common cuttlefish (0.85 μg g(-1) wet weight) and common octopus (0.64 μg g(-1) wet weight). The majority of the samples analyzed were in compliance with European Union legislation, except for a few cases. The calculated mean weekly intakes of Hg, Cd, and Pb through consumption of the fishery products tested were all below the legislated respective provisional tolerable weekly intakes. In general, the samples analyzed were considered safe to eat with regard to the metal concentrations found and the allowable intakes based on legislation. Nevertheless, the consumption of some species may be of significant importance for consumer health.