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Nowadays, hyaluronic acid (HA) eye drops are widely used to combat ophthalmic dry eye disease (DED). Till the date, almost all commercialized HA eye drops are single-ingredient despite not displaying significantly different clinical effects (Artelac Splash®). Consequently, scientists are making great efforts to combine HA with other compounds to overcome more successfully DED (trometamol in Hyabak®, sorbitol in HyloComod®). Gamma-polyglutamic acid (γ-PGA) is another novel polymer that could induce a powerful synergistic effect on HA for DED treatment. To the best of our knowledge, eye drops combining HA and γ-PGA neither have been marketed nor scientific studies have been published so far. Fortunately, DayDrop Advanced® eye drop has been recently commercialized with HA + γ-PGA technology. In this work, DayDrop Advanced®, Hyabak®, HyloComod® and Artelac Splash® were compared evaluating their efficacy to treat DED and residence time in eye due to their distinct physicochemical and rheological properties. As key research point, DayDrop Advanced® demonstrated an improved immediate hydration, protection against corneal dehydration, anti-inflammatory, anti-hyaluronidase and ocular mucoadhesion activities than the rest of artificial tears. These phenomena highlight new generation DayDrop Advanced® combining HA + γ-PGA technology as the leading eye drops to treat more durably and effectively DED.

A significant number of people worldwide suffers from knee osteoarthritis (KOA), a chronic and painful disease that is linked to aging, traumatological events and sports medicine. Clinical research indicates that KOA exhibit an altered synovial fluid (SF) with lower endogenous hyaluronic acid (HA) concentration and viscoelastic properties. Nowadays, viscosupplementation by intra-articular HA injections is the most common treatment to restore endogenous HA performance in osteoarthritic SF. In this work, TrHCROSS®, Durolane®, Regenflex®Bio-plus and Monovisc® commercial crosslinked HA viscosupplements were compared in vitro against enzymatic degradation. As key research point, TrHCROSS® demonstrated a considerably increased enzymatic stability compared to the rest of examined viscosupplements, which highlights TrHCROSS® prolonged residence time in joint space reducing more durably and effectively osteoarthritic knee pain. Subsequently, an in-depth physicochemical characterization was realized to support efficacy and stability results of viscosupplements. All in all, TrHCROSS®, developed by SARE® technology, was found to be more successful in treating more durably and effectively KOA based on the remarkable outcomes of conducted trials, which were appropriate findings for the current research investigation.

Prostate-specific antigen (PSA) is the gold-standard marker to screen prostate cancer (PCa) nowadays. Unfortunately, its lack of specificity and sensitivity makes the identification of novel tools to diagnose PCa an urgent medical need. In this context, microRNAs (miRNAs) have emerged as potential sources of non-invasive diagnostic biomarkers in several pathologies. Therefore, this study was aimed at assessing for the first time the dysregulation of the whole plasma miRNome in PCa patients and its putative implication in PCa from a personalized perspective (i.e., obesity condition). Plasma miRNome from a discovery cohort (18 controls and 19 PCa patients) was determined using an Affymetrix-miRNA array, showing that the expression of 104 miRNAs was significantly altered, wherein six exhibited a significant receiver operating characteristic (ROC) curve to distinguish between control and PCa patients (area under the curve [AUC] = 1). Then, a systematic validation using an independent cohort (135 controls and 160 PCa patients) demonstrated that miR-107 was the most profoundly altered miRNA in PCa (AUC = 0.75). Moreover, miR-107 levels significantly outperformed the ability of PSA to distinguish between control and PCa patients and correlated with relevant clinical parameters (i.e., PSA). These differences were more pronounced when considering only obese patients (BMI > 30). Interestingly, miR-107 levels were reduced in PCa tissues versus non-tumor tissues (n = 84) and in PCa cell lines versus non-tumor cells. In vitro miR-107 overexpression altered key aggressiveness features in PCa cells (i.e., proliferation, migration, and tumorospheres formation) and modulated the expression of important genes involved in PCa pathophysiology (i.e., lipid metabolism [i.e., FASN] and splicing process). Altogether, miR-107 might represent a novel and useful personalized diagnostic and prognostic biomarker and a potential therapeutic tool in PCa, especially in obese patients.

Cement removal during hip or knee arthroplasty revision surgery is technically demanding and prone to severe complications such as periprosthetic fractures, incomplete cement removal, or perforations. Several alternative techniques have been developed to enable complete, accurate, and safe removal of cement from bone, including osteotomies and cortical windows, endoscopic instruments, ultrasound devices, lithotripsy, and laser-assisted removal. We describe a cement-on-cement technique with a sterile, single-use tool for cement removal. The cement is removed piece by piece using a specifically designed device, without osteotomies or cortical windows.

Background: Dysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g. AR-v7/sst5TMD4/etc.) is associated to prostate-cancer (PCa) aggressiveness and/or castration-resistant PCa (CRPC) development, whether the molecular reason behind such phenomena might be linked to a dysregulation of the cellular machinery responsible for the splicing process [spliceosome-components (SCs) and splicing-factors (SFs)] has not been yet explored. Methods: Expression levels of 43 key SCs and SFs were measured in two cohorts of PCa-samples: 1) Clinically-localized formalin-fixed paraffin-embedded PCa-samples (n = 84), and 2) highly-aggressive freshly-obtained PCa-samples (n = 42). Findings: A profound dysregulation in the expression of multiple components of the splicing machinery (i.e. 7 SCs/19 SFs) were found in PCa compared to their non-tumor adjacent-regions. Notably, overexpression of SNRNP200, SRSF3 and SRRM1 (mRNA and/or protein) were associated with relevant clinical (e.g. Gleason score, T-Stage, metastasis, biochemical recurrence, etc.) and molecular (e.g. AR-v7 expression) parameters of aggressiveness in PCa-samples. Functional (cell-proliferation/migration) and mechanistic [gene-expression (qPCR) and protein-levels (western-blot)] assays were performed in normal prostate cells (PNT2) and PCa-cells (LNCaP/22Rv1/PC-3/DU145 cell-lines) in response to SNRNP200, SRSF3 and/or SRRM1 silencing (using specific siRNAs) revealed an overall decrease in proliferation/migration-rate in PCa-cells through the modulation of key oncogenic SVs expression levels (e.g. AR-v7/PKM2/XBP1s) and alteration of oncogenic signaling pathways (e.g. p-AKT/p-JNK). Interpretation: These results demonstrate that the spliceosome is drastically altered in PCa wherein SNRNP200, SRSF3 and SRRM1 could represent attractive novel diagnostic/prognostic and therapeutic targets for PCa and CRPC. Keywords: Prostate cancer, Splicing, Spliceosome, SNRNP200, SRSF3, SRRM1, Therapeutic target

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths among men. Consequently, the identification of novel molecular targets for treatment is urgently needed to improve patients' outcomes. Our group recently reported that some elements of the cellular machinery controlling alternative-splicing might be useful as potential novel therapeutic tools against advanced PCa. However, the presence and functional role of RBM22, a key spliceosome component, in PCa remains unknown. Therefore, RBM22 levels were firstly interrogated in 3 human cohorts and 2 preclinical mouse models (TRAMP/Pbsn-Myc). Results were validated in in silico using 2 additional cohorts. Then, functional effects in response to RBM22 overexpression (proliferation, migration, tumorspheres/colonies formation) were tested in PCa models in vitro (LNCaP, 22Rv1, and PC-3 cell-lines) and in vivo (xenograft). High throughput methods (ie, RNA-seq, nCounter PanCancer Pathways Panel) were performed in RBM22 overexpressing cells and xenograft tumors. We found that RBM22 levels were down-regulated (mRNA and protein) in PCa samples, and were inversely associated with key clinical aggressiveness features. Consistently, a gradual reduction of RBM22 from non-tumor to poorly differentiated PCa samples was observed in transgenic models (TRAMP/Pbsn-Myc). Notably, RBM22 overexpression decreased aggressiveness features in vitro, and in vivo. These actions were associated with the splicing dysregulation of numerous genes and to the downregulation of critical upstream regulators of cell-cycle (i.e., CDK1/CCND1/EPAS1). Altogether, our data demonstrate that RBM22 plays a critical pathophysiological role in PCa and invites to suggest that targeting negative regulators of RBM22 expression/activity could represent a novel therapeutic strategy to tackle this disease., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is one of the most common cancers types among men. Development and progression of PCa is associated with aberrant expression of oncogenic splicing-variants (eg, AR-v7), suggesting that dysregulation of the splicing process might represent a potential actionable target for PCa. Expression levels (mRNA and protein) of SF3B1, one of the main components of the splicing machinery, were analyzed in different cohorts of PCa patients (clinically localized [n = 84], highly aggressive PCa [n = 42], and TCGA dataset [n = 497]). Functional and mechanistic assays were performed in response to pladienolide-B in nontumor and tumor-derived prostate cells. Our results revealed that SF3B1 was overexpressed in PCa tissues and its levels were associated with clinically relevant PCa-aggressive features (eg, metastasis/AR-v7 expression). Moreover, inhibition of SF3B1 activity by pladienolide-B reduced functional parameters of aggressiveness (proliferation/migration/tumorspheres-formation/apoptosis) in PCa cell lines, irrespective of AR-v7 expression, and reduced viability of primary PCa cells. Antitumor actions of pladienolide-B involved: (1) inhibition of PI3K/AKT and JNK signaling pathways, (2) modulation of tumor markers and splicing variants (AR-v7/In1-ghrelin), and (3) regulation of key components of mRNA homeostasis-associated machineries (spliceosome/SURF/EJC). Altogether, our results demonstrated that SF3B1 is overexpressed and associated with malignant features in PCa, and its inhibition reduces PCa aggressiveness, suggesting that SF3B1 could represent a novel prognostic biomarker and a therapeutic target in PCa., (Copyright © 2019 Elsevier Inc. All rights reserved.)