Novel Ti6Al4V Surface Treatment for Subperiosteal Dental Implants (Part II): Matrix Deposition and Osteogenic Markers Valentina Schiavoni, Lucia Memé, Giovanni Tossetta, Daniela Marzioni, Fabrizio Bambini, et al. Materials, 2026 In a previous study, we demonstrated that a novel surface treatment applied to laser-melted Ti6Al4V substrates supports osteoblast-like cell adhesion, proliferation, and the activation of early osteogenic pathways. Building on these preliminary findings, the present work aimed to further investigate the ability of the same surface to promote extracellular matrix (ECM) deposition, organization, and osteogenic maturation, which are critical events for the establishment of a stable bone–implant interface in subperiosteal dental implants. Human osteoblast-like MG-63 cells were cultured on Ti6Al4V discs subjected to different surface treatments, including a proprietary surface modification (ATcs) specifically designed for subperiosteal applications. ECM formation and maturation were evaluated through scanning electron microscopy coupled with energy-dispersive spectroscopy, immunofluorescence, and semiquantitative analyses of osteogenic markers type I collagen (COL1A1), secreted protein acidic and rich in cysteine (SPARC), and dentin matrix protein 1 (DMP1) through Western blotting. The results showed that, while all tested surfaces supported cell adhesion, the ATcs surface promoted a distinct osteogenic profile characterized by enhanced DMP1 expression, organized collagen deposition, and the formation of calcium–phosphate–rich mineralized structures. Compared to surfaces that primarily stimulated cell proliferation or early matrix production, ATcs appeared to favour progression toward late-stage osteogenic maturation and matrix mineralization. Taken together, these findings extend our previous observations and indicate that this novel surface treatment not only supports osteoblast viability and early differentiation but also promotes extracellular matrix maturation, a key prerequisite for effective osseointegration. Although further in vivo studies are required, the present data provide additional biological rationale for the use of ATcs-treated Ti6Al4V surfaces in next-generation custom-made subperiosteal implant designs.
Short and Long Non-Coding RNAs in Renal Cell Carcinoma Monia Cecati, Valentina Pozzi, Valentina Schiavoni, Giuseppina Barrasso, Veronica Pompei, et al. Non Coding RNA, 2026 Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shape tumor behavior and therapeutic response in RCC. This review summarizes current knowledge on the biological and clinical relevance of ncRNAs in RCC, highlighting their dual roles as oncogenic drivers or tumor suppressors through the modulation of pathways involved in proliferation, apoptosis, angiogenesis, invasion, immune evasion, metabolic reprogramming, and ferroptosis. Particular emphasis is placed on mechanistically defined ncRNA regulatory axes controlling ferroptosis, autophagy, metabolic reprogramming, and immune escape, as well as on ncRNA-mediated intercellular communication via extracellular vesicles, which promotes the dissemination of resistance to targeted therapies. The review also addresses ncRNA-based diagnostic and prognostic applications, including miRNA signatures capable of discriminating RCC subtypes and circulating ncRNAs as minimally invasive biomarkers. Moreover, the manuscript discusses ncRNA-mediated mechanisms of resistance to targeted therapies such as sunitinib, sorafenib, and axitinib, emphasizing regulatory networks involving miRNA targets, lncRNA–miRNA sponging, RNA-binding proteins, extracellular vesicle transfer, and epigenetic modulation. Emerging therapeutic opportunities are also addressed, including strategies aimed at inhibiting oncogenic ncRNAs or restoring tumor-suppressive ncRNAs to enhance drug sensitivity and improve patient stratification.
Dose-dependent effects of curcumin on 22Rv1 prostate cancer cell line Giovanni Tossetta, Sonia Fantone, Elena Marinelli Busilacchi, Daniela Marzioni, Roberta Mazzucchelli Molecular Biology Reports, 2025 Background Prostate cancer (PCa) is the second most frequent cancer type in the male population over 66 years. Curcumin is a polyphenolic natural compound extract from the rhizomes of Curcuma longa Linn (Zingiberaceae family) which showed important anticancer effects by inhibiting cell proliferation and inducing apoptosis in several cancer types. Recently, some studies reported that oral curcumin lowered PSA levels, but it did not modify the clinical outcomes in patients with prostate cancer who received intermittent androgen deprivation (IAD). Other studies reported that high concentrations of curcumin were toxic for patients. Methods and results In this study we showed that low doses of curcumin can induce senescence-like effects in 22Rv1 cell line while higher concentrations have cytotoxic effects. Five,15 and 30 µM curcumin blocked cell cycle in G2/M phase but only 15 and 30 µM curcumin induced cell death. In addition, an increased expression of p21, a known senescence marker, was detected in 22Rv1 cells treated with curcumin in every experimental condition. However, the expression of p16, another known senescence marker, increased only to 30 µM curcumin. Conclusion In the context of personalized approach in PCa care, we suggest that the appropriate concentration of curcumin used in combination with radiotherapy or with androgen deprivation therapy (ADT) could be taken into consideration.
Effect of natural compounds on NRF2/KEAP1 signaling in periodontitis: a potential use to prevent age-related disorders Giovanni Tossetta, Sonia Fantone, Fabiola Olivieri, Roberta Mazzucchelli, Lucrezia Togni, et al. Molecular Biology Reports, 2025 40% of the population over 60 years of age is affected by periodontitis which is characterized by chronic inflammation, periodontal damage and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/ Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis modulating redox balance and periodontium inflammation. However, NRF2 expression decreases in gingival tissues of severe periodontitis patients while Reactive Oxygen Species (ROS) levels are increased during periodontitis. ROS and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory cytokines, then causing periodontal inflammation and favoring alveolar bone loss (due to excessive osteoclast formation and activation). Periodontitis has also been associated to the development of age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases since the increased cytokines levels and the bacteria themselves present in the periodontium can easily reach the brain due to their anatomical proximity. Thus, periodontitis could be considered a risk factor for the development of Alzheimer’s and Parkinson’s diseases. In this review we explored the role of NRF2/KEAP1 signaling activation in in vitro and in vivo models of periodontitis to suggest potential treatments of periodontitis and avoid/delay the development of age-related neurodegenerative diseases.
Importance of STAT3 signaling in preeclampsia (Review) Daniela Marzioni, Federica Piani, Nicoletta Di Simone, Stefano Giannubilo, Andrea Ciavattini, et al. International Journal of Molecular Medicine, 2025 Placentation is a key process that is tightly regulated that ensures the normal placenta and fetal development. Preeclampsia (PE) is a hypertensive pregnancy-associated disorder characterized by increased oxidative stress and inflammation. STAT3 signaling plays a key role in modulating important processes such as cell proliferation, differentiation, invasion and apoptosis. The present review aimed to analyse the role of STAT3 signaling in PE pregnancies, discuss the main natural and synthetic compounds involved in modulation of this signaling both in vivo and in vitro and summarize the main cellular modulators of this signaling to identify possible therapeutic targets and treatments to improve the outcome of PE pregnancies.
Role of SLC7A11/xCT in Ovarian Cancer Sonia Fantone, Federica Piani, Fabiola Olivieri, Maria Rita Rippo, Angelo Sirico, et al. International Journal of Molecular Sciences, 2024
The Role of NQO1 in Ovarian Cancer Giovanni Tossetta, Sonia Fantone, Gaia Goteri, Stefano Raffaele Giannubilo, Andrea Ciavattini, et al. International Journal of Molecular Sciences, 2023
Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) signal through MAPK/ERK pathway in human prostate tissues: A morphological and biomolecular study European Journal of Histochemistry, 2020
RKIP and cytotrophoblast motility Pasquapina Ciarmela, Daniela Marzioni, Md. Soriful Islam, Peter Clarke Gray, Luigi Terracciano, et al. Journal of Cellular Physiology, 2012
Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic diseases Histology and Histopathology, 2009
PUNLMP or not PUNLMP? This is the problem Analytical and Quantitative Cytology and Histology, 2009
