Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review

Since the discovery of the Hedgehog(Hh)pathway in drosophila melanogaster,our knowledge of the role of Hh in embryonic development,inflammation,and cancerogenesis in humans has dramatically increased over the last decades.This is the case especially concerning the pancreas,however,real therapeutic breakthroughs are missing until now.In general,Hh signaling is essential for pancreatic organogenesis,development,and tissue maturation.In the case of acute pancreatitis,Hh has a protective role,whereas in chronic pancreatitis,Hh interacts with pancreatic stellate cells,leading to destructive parenchym fibrosis and atrophy,as well as to irregular tissue remodeling with potency of initiating cancerogenesis.In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment.The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials(phases 1 and 2).Furthermore,a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach.In this review,we give a structured survey of the role of the Hh pathway in pancreatic development,pancreatitis,pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

Role of histone deacetylases in pancreas: Implications for pathogenesis and therapy

In the last years, our knowledge of the pathogenesis in acute and chronic pancreatitis(AP/CP) as well as in pancreatic cancerogenesis has significantly diversified. Nevertheless, the medicinal therapeutic options are still limited and therapeutic success and patient outcome are poor. Epigenetic deregulation of gene expression is known to contribute to development and progression of AP and CP as well as of pancreatic cancer. Therefore, the selective inhibition of aberrantly active epigenetic regulators can be an effective option for future thera-pies. Histone deacetylases(HDACs) are enzymes that remove an acetyl group from histone tails, thereby causing chromatin compaction and repression of transcri-ption. In this review we present an overview of the currently available literature addressing the role of HDACs in the pancreas and in pancreatic diseases. In pancreatic cancerogenesis, HDACs play a role in the important process of epithelial-mesenchymal-transition, ubiquitin-proteasome pathway and, hypoxia-inducible-factor-1-angiogenesis. Finally, we focus on HDACs as potential therapeutic targets by summarizing currently available histone deacetylase inhibitors.

Additive Manufacturing of Ceramics from Liquid Feedstocks

In this review,we summarize the research activities carried out by our research group at the University of Padova on the additive manufacturing of ceramics from liquid feedstocks.Particularly,we evaluate the use of preceramic polymers,geopolymers,and sol-gel solutions.We mainly focus on processing with liquid feedstocks because they have some advantages with respect to slurry-based feedstocks in which powders are present.Particularly,lower viscosity,enhanced transparency,and lack of scattering and sedimentation are advantageous features for vat photopolymerization processes,whereas the absence of particulates reduces clogging problems at the nozzle for extrusion-based processes.Simultaneously,preceramic polymers and geopolymers have some limitations in terms of the range of ceramic compositions that can be obtained;sol-gel solutions are intrinsically unstable,whereas printed objects suffer from drying issues.Nevertheless,we successfully produced high-quality parts using a variety of additive manufacturing techniques,some of which(e.g.,volumetric additive manufacturing)have been proposed for the fabrication of ceramic components for the first time.