Marine-Derived Secondary Metabolites as Promising Epigenetic Bio-Compounds for Anticancer Therapy

Sessile organisms such as seaweeds, corals, and sponges continuously adapt to both abiotic and biotic components of the ecosystem. This extremely complex and dynamic process often results in different forms of competition to ensure the maintenance of an ecological niche suitable for survival. A high percentage of marine species have evolved to synthesize biologically active molecules, termed secondary metabolites, as a defense mechanism against the external environment. These natural products and their derivatives may play modulatory roles in the epigenome and in disease-associated epigenetic machinery. Epigenetic modifications also represent a form of adaptation to the environment and confer a competitive advantage to marine species by mediating the production of complex chemical molecules with potential clinical implications. Bioactive compounds are able to interfere with epigenetic targets by regulating key transcriptional factors involved in the hallmarks of cancer through orchestrated molecular mechanisms, which also establish signaling interactions of the tumor microenvironment crucial to cancer phenotypes. In this review, we discuss the current understanding of secondary metabolites derived from marine organisms and their synthetic derivatives as epigenetic modulators, highlighting advantages and limitations, as well as potential strategies to improve cancer treatment

CEUS Retrograde Cystography Is Helpful in Percutaneous Drainage of Complex Posttransplant Lymphocele

After monolateral dual kidney transplantation, a 69 years old male patient developed symptomatic lymphocele with mild hydroureteronephrosis, impaired renal function, and right inferior limb oedema. A percutaneous ultrasound-guided drainage of the fluid collection was planned, but the complex mutual relations between the collection and the renal hilus did not allow to identify a suitable route for a safe drainage insertion during conventional ultrasound examination. A retrograde cystography using echographic contrast agent was, therefore, performed, and it clarified the position of both ureters and the renal vessels, permitting an harmless ultrasound-guided percutaneous lymphocele drainage. In conclusion contrast-enhanced ultrasound retrograde cystography may be helpful in percutaneous drainage of complex posttransplant lymphocele

Combined Approach to Treat Medication-Related Osteonecrosis of the Jaws.

Introduction: The proper therapeutic plan for medication-related osteonecrosis of the Jaw (MRONJ) is still lacking long-term data up to today. They were several high-technological appliances proposed for the different intervention steps, in addition to tissue repair promoters. The reason for proposing an integrated technique is justified, beyond better compliance of the patients associated to the pain and inflammation reduction and bleeding control, there is also achieving better hard and soft tissues healing.Methods: Patients diagnosed with bisphosphonates-related osteonecrosis of the jaws (BRONJ) at the Odontostomatology and Maxillo-Facial Surgery Unit of the Hospital of Piacenza undergone surgical intervention. The intervention was performed by using different devices: Piezosurgery for removing the necrotic bone tissue and for obtaining the bone specimen essential for histological analysis; Er:YAG laser (2940 nm) to vaporize necrotic hard tissue until reaching the bleeding bone; platelet-rich plasma (PRP) to stimulate hard and soft tissue healing; and finally diode laser (808 nm) to perform a biostimulation of the surgical site.Results: All treated patients demonstrated a good postoperative comfort even without using painkillers, no bleeding, and a fast healing process. Most of the patients (92.85%) reached complete healing with a minimum follow up at 6 months. Histological exams demonstrated a good quality without artifacts.Conclusion: Sequential utilization of different high-technologies devices during all the steps of MRONJ treatment allows to perform a faster and less invasive surgery with a more comfortable postoperative healing process and it may represent a new and original approach for treating this severe adverse event

Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine

The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase‐independent mechanism. Inhibition of this complex in a model of glutamate‐induced cell death in HT‐22 neuronal cells by an AIF peptide (AIF(370‐394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia‐ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH‐SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370‐394) confers resistance to STS‐induced apoptosis in SH‐SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD

Knockout of the Glucocorticoid Receptor Impairs Reproduction in Female Zebrafish

none8The pleiotropic effects of glucocorticoids in metabolic, developmental, immune and stress response processes have been extensively investigated; conversely, their roles in reproduction are still less documented. It is well known that stress or long-lasting therapies can cause a strong increase in these hormones, negatively affecting reproduction. Moreover, the need of glucocorticoid (GC) homeostatic levels is highlighted by the reduced fertility reported in the zebrafish glucocorticoid receptor mutant (nr3c1ia30/ia30) line (hereafter named gr-/-). Starting from such evidence, in this study, we have investigated the role of glucocorticoid receptor (Gr) in the reproduction of female zebrafish. Key signals orchestrating the reproductive process at the brain, liver, and ovarian levels were analyzed using a multidisciplinary approach. An impairment of the kiss-GnRH system was observed at the central level in (gr-/-) mutants as compared to wild-type (wt) females while, in the liver, vitellogenin (vtg) mRNA transcription was not affected. Changes were instead observed in the ovary, particularly in maturing and fully grown follicles (classes III and IV), as documented by the mRNA levels of signals involved in oocyte maturation and ovulation. Follicles isolated from gr-/- females displayed a decreased level of signals involved in the acquisition of competence and maturation, causing a reduction in ovulation with respect to wt females. Fourier transform infrared imaging (FTIRI) analysis of gr-/- follicle cytoplasm showed major changes in macromolecule abundance and distribution with a clear alteration of oocyte composition. Finally, differences in the molecular structure of the zona radiata layer of gr-/- follicles are likely to contribute to the reduced fertilization rate observed in mutants.openMaradonna, Francesca; Gioacchini, Giorgia; Notarstefano, Valentina; Fontana, Camilla Maria; Citton, Filippo; Dalla Valle, Luisa; Giorgini, Elisabetta; Carnevali, OlianaMaradonna, Francesca; Gioacchini, Giorgia; Notarstefano, Valentina; Fontana, Camilla Maria; Citton, Filippo; Dalla Valle, Luisa; Giorgini, Elisabetta; Carnevali, Olian

Optical techniques for the characetrization of surface-subsurface defects in painted layers

3D optical techniques are proven to be useful for the study of the artwork's surface morphology because they allow noncontact and noninvasive measurements. Detailed topographic analysis of the surface including a quantitative evaluation of defects related to the painting layers can be performed by means of holographic conoscopy on a micron scale. Moreover, artwork surfaces can be examined with suitable 2D optical techniques in the IR range to investigate defects at a subsurface level. In particular, thermography in the Mid-IR band 3-5 micron allows the detection and spatial mapping at a suitable resolution of the delamination of painted layers. An integrated model of the surface-subsurface defect distribution can be obtained by superimposing the results of the two above techniques, for a more effective analysis and monitoring of the delamination decay typology according to the specific case study. The delamination of organic paint layers from inorganic support is a decay that affects many wall paintings based on both traditional (oil and tempera) and synthetic media (acrylic and vinyl copolymers). Defining the factors that cause delamination, finding out strategies to restore the adhesion between paint layers and support, and monitoring the restoration intervention are fundamental conservation objectives. This paper investigates the feasibility of a joint use of holographic conoscopy and IR thermography for exploring the delamination decay typology of ad hoc laboratory samples. Set up includes a scanning micro-profilometer, and a thermal PtSi camera with a controlled IR source to provide heating stimulation