The role of the two splice variants and extranuclear pathway on Ki-67 regulation in non-cancer and cancer cells

Ki-67 is a nuclear protein that has been used in cancer diagnostic because of its specific cell-cycle dependent expression profile. After quantifying and characterising the expression level of Ki-67, as a function of the cell cycle, we found out that the two main splice variants of the protein (i.e. α and β) are differently regulated in non-cancerous and cancerous cells both at mRNA and protein level. We were able to correlate the presence of the α variant of the protein with the progression through the interphase of cell cycle. We also observed that the different expression profiles correspond to different degradation pathways for non-cancerous and cancerous cells. Furthermore, Ki-67 is continuously regulated and degraded via proteasome system in both cell types, suggesting an active control of the protein. However we also observed a putative extranuclear elimination pathway of Ki-67 where it is transported to the Golgi apparatus. Our evidence in the different expression of the splice variants may represent a milestone for the development of new targets for cancer diagnostic and prognostic. Additionally, the unexpected extranuclear elimination of Ki-67 strongly suggests that this protein must be looked at also outside of the "nuclear box", as thought to date

Engineering polymeric nanosystems against oral diseases

Nanotechnology and nanoparticles (NPs) are at the forefront of modern research, par-ticularly in the case of healthcare therapeutic applications. Polymeric NPs, specifically, hold high promise for these purposes, including towards oral diseases. Careful optimisation of the production of polymeric NPs, however, is required to generate a product which can be easily translated from a laboratory environment to the actual clinical usage. Indeed, considerations such as biocompati-bility, biodistribution, and biodegradability are paramount. Moreover, a pre-clinical assessment in adequate in vitro, ex vivo or in vivo model is also required. Last but not least, considerations for the scale-up are also important, together with an appropriate clinical testing pathway. This review aims to eviscerate the above topics, sourcing at examples from the recent literature to put in context the current most burdening oral diseases and the most promising polymeric NPs which would be suitable against them

Use of selected lactic acid bacteria for the fermentation of legume-based water extracts

In this study, the effect of selected Lactobacillus acidophilus ATCC 4356, Limosilactobacillus fermentum DSM 20052, and Lacticaseibacillus paracasei subsp. paracasei DSM 20312 strains on the sensory characteristics, and protein and amino acid content of fermented water extracts derived from lupin, pea, and bean grains is reported. Even though all strains were able to grow over 7 log cfu mL(-1) and to decrease pH in the range of -0.52 to -1.25 within 24 h, the release of an unpleasant ferric-sulfurous off-odor from the fermented bean water extract prohibited further characterization. Lupin and pea grain-based beverages underwent an in-depth sensory evaluation using a simplified check-all-that-apply (CATA) method, finding new and appreciable sensory notes such as cooked ham, almonds, and sandalwood. Fermented lupin water extract showed higher total protein content (on average, 0.93 mg mL(-1)) in comparison to that of pea grains (on average, 0.08 mg mL(-1)), and a free amino acid content (on average, 3.9 mg mL(-1)) close to that of cow milk. The concentrations of these nutrients decreased during refrigerated storage, when the lactic acid bacteria load was always higher than 7 log cfu mL(-1). The results of this study indicated that lactic fermentation improves the sensory characteristics of these innovative legume-based beverages, which sustained high loads of viable lactobacilli up to the end of cold storage

Polypyrrole and polyaniline nanocomposites with high photothermal conversion efficiency

The simple and scalable synthesis of poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC)-coated conducting polymer (CP) nanocomposites is described. These functional nanocomposites exhibit tunable absorption in the near-infrared region with relatively high photothermal efficiencies. More importantly, their potential for bio-imaging and therapeutic treatment is proven by cellular uptake and cytotoxicity studies

Engineering Polymeric Nanosystems against Oral Diseases

Nanotechnology and nanoparticles (NPs) are at the forefront of modern research, particularly in the case of healthcare therapeutic applications. Polymeric NPs, specifically, hold high promise for these purposes, including towards oral diseases. Careful optimisation of the production of polymeric NPs, however, is required to generate a product which can be easily translated from a laboratory environment to the actual clinical usage. Indeed, considerations such as biocompatibility, biodistribution, and biodegradability are paramount. Moreover, a pre-clinical assessment in adequate in vitro, ex vivo or in vivo model is also required. Last but not least, considerations for the scale-up are also important, together with an appropriate clinical testing pathway. This review aims to eviscerate the above topics, sourcing at examples from the recent literature to put in context the current most burdening oral diseases and the most promising polymeric NPs which would be suitable against them

Macrophage Targeting pH Responsive Polymersomes for Glucocorticoid Therapy

Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)–poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC–PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy

Synergistic effect induced by gold nanoparticles with polyphenols shell during thermal therapy: Macrophage inflammatory response and cancer cell death assessment

Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment

Osservazioni sulla mortalita di ircinia spinosula (schmidt) ed ircinia sp. (porifera, demospongiae) nell’insenatura della strea di porto cesareo

EnA long-term investigation (1994-1996) was carried out on two species of Ircinia, I. spinosula and Ircinia sp., coexisting in a Mediterranean coastal basin (Porto Cesareo, South-Western Apulia). During 1994 both species were affected by a disease which caused a decrease of their density. In I. spinosula the maximum decrement was observed in January 1996 (about 27%), while, in the same period Ircinia sp. was almost completely disappeared from the investigated area. In July1996 a successive slow restarting of the two species was observed. SEM observations of the skeleton of damaged specimens showed a decay of spongine fibres. Even though these ones were frequently broken, they did not show grooves in their external surface, nor they seemed excavated inside. Tissue reparation processes were observed; they seemed to consist in the isolation of affected areas, permitting a recovery and regeneration of many specimens.ItE’ stato condotto un monitoraggio temporale (1994-1996) su due specie del genere Ircinia, I. spinosula e Ircinia sp,, coesistenti in un bacino costiero mediterraneo (Porto Cesareo, Puglia Sud-Occidentale). Ne1 1994 entrambe le specie sono state colpite da una malattia che ha provocato un decremento della loro densita. In I. spinosula il decremento massimo è stato osservato in gennaio 1996 (circa il27%), mentre nello stesso periodo Ircinia sp è quasi del tutto scomparsa dall’area d’indagine. Nel luglio 1996 è stata osservata una successiva e lenta ripresa delle due specie. Le indagini ultrastrutturali (SEM) hanno permesso di osservare che in entrambe le specie lo scheletro degli esemplari danneggiati presentava una trama discontinua con le fibre di spongina frequentemente spezzate. Sebbene tali fibre risultassero sfaldate non apparivano mai erose al loro interno. Sono stati osservati, inoltre, probabili meccanismi di riparo dei tessuti; tali meccanismi, consistenti nell'isolamento delle aree affette da malattia, sono probabilmente alla base dei processi di ripresa e di rigenerazione di molti esemplari

Infliximab in the treatment of Crohn's disease

The recent introduction of infliximab, a chimeric monoclonal antibody against tumor necrosis factor-alpha, has greatly modified the treatment of Crohn's disease (CD). Data from the literature show encouraging results after intravenous infusion both for closure of intestinal or perianal fistulas and for induction and maintenance of remission in patients with moderate to severe intestinal disease unresponsive to other treatments. However, some contraindications such as fibrostenosing CD and sepsis have been identified. In addition, the data on long-term outcomes and safety is still limited. Our initial experience showed that in selected cases local injection of infliximab is effective in the treatment of complex perianal disease offering the possibility of using such treatment even in small bowel obstructing disease with minimal systemic effects. This paper analyzes the state of the use of both intravenous and local injection of infliximab in patients with CD