Fidia Farmaceutici (Italy)

To compare two sodium hyaluronate formulations (HYMOVIS® ONE and MONOVISC®) for single intra-articular (IA) injection in patients with knee osteoarthritis pain. This randomized, controlled study included 347 subjects allocated to two treatment arms: HYMOVIS® ONE (n = 175) and MONOVISC® (n = 172). The primary endpoint assessed non-inferiority of HYMOVIS® ONE versus MONOVISC® based on change from baseline in the WOMAC LK3.1 A1 Pain subscale. Secondary outcomes evaluated patient response using OMERACT-OARSI criteria, changes in WOMAC stiffness and function scores, health-related quality of life (SF-12), global assessments by patients and clinicians, and rescue medication use. The mean WOMAC LK3.1 A1 walking pain subscale score decreased significantly from baseline at week 12 in both groups, with reductions of 65 % for HYMOVIS® ONE and 66 % for MONOVISC®. At week 26, reductions were 73 % for HYMOVIS® ONE and 69 % for MONOVISC®. The non-inferiority test yielded a p-value of 0.0003. Clinically significant change from baseline was observed for all secondary endpoints. For the WOMAC LK3.1 Function subscale, the comparison between groups at week 26 showed a statistically significant difference (p = 0.0367) favoring HYMOVIS® ONE. Both treatments were well tolerated. A single injection of HYMOVIS® ONE was well tolerated and non-inferior to MONOVISC®, with improvements across all study endpoints maintained through 26 weeks, indicating sustained symptomatic relief of knee OA. NCT06528600 (www.clinicaltrials.gov).

Background/Objectives: Sulfated hyaluronic acid (sHA) is a chemically modified derivative of native hyaluronic acid (HA), characterized by enhanced physicochemical stability and increased biological activity. Glycosaminoglycans (GAGs), including HA, are key regulators of skin structure, hydration, and immune homeostasis. This review aims to critically summarize current knowledge on the structural and functional properties of GAGs—particularly HA and its sulfated forms—and to explore their potential dermatological applications in skin aging and inflammatory diseases such as atopic dermatitis, psoriasis, and acne. Methods: A narrative literature review was conducted using PubMed and Scopus databases up to June 2025, including experimental, preclinical, and clinical studies investigating the biological effects, mechanisms of action, and dermatological uses of sHA compared with native HA and other HA derivatives. Results: Compared with HA, sHA demonstrates increased enzymatic resistance, higher charge density, and improved water-binding and antioxidant capacity. These properties contribute to the restoration of skin barrier function, modulation of oxidative stress and inflammation, and promotion of extracellular matrix remodeling. Preclinical evidence supports the efficacy of sHA in reducing dryness, irritation, and inflammatory responses in atopic dermatitis, psoriasis, and acne. Preliminary findings also suggest potential benefits in wound healing and skin barrier repair. Conclusions: sHA represents a promising multifunctional molecule in dermatology and cosmetology, capable of reducing inflammation and supporting tissue regeneration. However, current evidence remains limited to preliminary studies. Future controlled clinical trials are required to confirm efficacy, optimize formulations, and establish standardized treatment protocols.

To evaluate the safety and efficacy of intra-articular autologous transplantation of adipose-derived connective tissue micrografts rich in stromal vascular fraction (CTM-SVF), obtained using an enzyme-free system (Hy-Tissue® SVF) for knee osteoarthritis (OA). Thirty patients (mean age of 53.3 ± 6.4 years) with Kellgren-Lawrence grade I to III knee OA received a single intra-articular injection of autologous CTM-SVF prepared with the Hy-Tissue SVF concentration system. Follow-ups were set at 3-, 6- and 12-month postinjection. Outcome measures included knee injury and osteoarthritis outcome score (KOOS), pain relief (NRS-11), quality of life (EQ-5D index), magnetic resonance imaging (MRI) scans (whole-organ magnetic resonance imaging score-WORMS, T2 mapping), OA serum biomarkers, safety and local tolerability. One patient discontinued prematurely. KOOS improved significantly, with the highest mean score (68.7 ± 14.9) at 3 months and the majority of patients achieving a ≥ 9-point increase from baseline. Results were maintained through 12 months. NRS-11 and EQ-5D also improved through 12 months, with more than 80% of patients meeting the NRS-11 MCID at every timepoint. EQ-VAS, however, showed only a modest responder rate (10%). MRI revealed improvements in T2 relaxation times, while OA serum biomarkers (evaluated at 3 months postinjection) indicated a significant decrease in Procollagen II N-Terminal Propeptide levels. No device-related adverse events (ADEs) were observed. The majority of adverse events (AEs) recorded during the study were mild and transient, none were classified as serious and resolved within a short period. Intra-articular injection of autologous CTM-SVF, obtained the Hy-Tissue-SVF system, proved to be effective and safe for managing knee OA symptoms and improving mobility, up to 12 months. Clinically significant pain relief and quality of life improvement were observed, particularly in the short term, with a gentle reduction of the scores over time. Larger controlled trials are required to confirm treatment durability. Level II.

Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology.

ABSTRACT This study evaluated the flushing performance of a commercial dripline system (Toro Neptune PC 16 mm) through indoor and outdoor experiments to determine the optimal flow conditions for sediment removal. Indoor tests demonstrated that flow rates of 6.3–9.8 L/min (velocities of 0.8–1.1 m/s) effectively detached particles, with the jet throw distance serving as a practical indicator of flushing efficiency. Outdoor trials revealed that increased flow during flushing resulted in head losses and pressure drops below the anti‐drip threshold, leading to emitter shutdown and a reduction in dripline length by up to 20%. To improve performance, hydraulic simulations recommended shortening the dripline by 10% and increasing the nominal pressure by 0.1 MPa. These adjustments enhanced the pressure distribution and maintained emitter functionality, improving the overall flushing performance.

O presente estudo discute a gestão participativa na saúde coletiva, analisando seus caminhos para a efetivação de políticas públicas locais. A pesquisa foi desenvolvida por meio de uma revisão da literatura, utilizando os indexadores Google Scholar, Scopus e Web of Science para selecionar artigos relevantes. Foram considerados estudos publicados nos últimos 5 anos, em português, inglês e espanhol. Os resultados apontam que a participação social, a educação permanente e o uso de tecnologias digitais são estratégias fundamentais para o fortalecimento das políticas públicas no Sistema Único de Saúde (SUS). No entanto, desafios como a intensificação do trabalho no serviço público, a precarização das condições laborais e a privatização de funções sociais dificultam a consolidação de uma gestão efetiva. Questões relacionadas à saúde mental e à saúde ambiental também demandam políticas mais robustas. Conclui-se que a gestão participativa deve ser sustentada pela articulação entre diferentes setores, valorizando a inclusão e a inovação, para garantir um sistema de saúde mais justo, integral e sustentável.

Gastrointestinal neuroendocrine tumors (GI-NETs) lack effective targeted options beyond somatostatin analogs and mTOR inhibitors. Spleen tyrosine kinase (SYK) is a non-receptor kinase with emerging roles in solid tumors and available small-molecule inhibitors. We explored whether SYK is a plausible therapeutic target in GI-NET using two human cell lines. SYK expression in GI-NET cells was confirmed by immunofluorescence. Cells were exposed to a selective SYK inhibitor (BI-1002494), and proliferation was quantified using both 2D and 3D models. Both GI-NET models expressed SYK and exhibited reduced growth upon SYK blockade, with dose-dependent suppression of viability and increased cytotoxicity relative to vehicle. In spheroid assays, morphologic changes and reduced size were observed. These pilot data suggest SYK as a targetable vulnerability in GI-NET and support formal dose–response studies, genetic validation, and combination strategies with standard-of-care agents. Given the clinical availability of SYK inhibitors, these findings provide a rationale for translational studies in GI-NET.

There is a large demand for nutraceuticals in the market and studies related to their action are needed. In this paper, the antimicrobial activity and the immunomodulatory effect of a nutraceutical formulation containing 14.39% of ascorbic acid, 7.17% of coenzyme Q10, 1.33% of Echinacea polyphenols, 0.99% of pine flavan-3-ols, 0.69% of resveratrol and 0.023% of Echinacea alkylamides were studied using in vitro assays and cell-based metabolomics. Chromatographic analysis allowed us to study the nutraceutical composition. The antibacterial activity was evaluated on S. aureus, K. pneumoniae, P. aeruginosa, E. coli, H. influenzae, S. pyogenes, S. pneumoniae and M. catarrhalis. The immunomodulatory activity was assessed on human macrophages and dendritic cells. The production of IL-1β, IL-12p70, IL-10 and IL-8 was evaluated on culture medium by ELISA and the activation/maturation of dendritic cells with cytofluorimetric analysis. Treated and untreated macrophages and dendritic cell lysates were analysed by liquid chromatography coupled with high-resolution mass spectrometry, and results were compared using multivariate data analysis to identify biological markers related to the treatment with the food supplement. The food supplement decreased K. pneumoniae, P. aeruginosa, E. coli, Methicillin-resistant Staphylococcus aureus (MRSA) and M. catharralis growth, reduced the inflammatory response in macrophages exposed to lipopolysaccharide (LPS) and modulated the activation and maturation of the dendritic cells. Oxidized phospholipids were identified as the main biological markers of treated cell lysates, compared with controls.

The inhibition of human urokinase-type plasminogen activator (huPA), a serine protease that plays an important role in pericellular proteolysis, is a promising strategy to decrease the invasive and metastatic activity of tumour cells. However, the generation of selective small molecule huPA inhibitors has proven to be challenging due to the high structural similarity of huPA to other paralogue serine proteases. Efforts to generate more specific therapies have led to the development of cyclic peptide-based inhibitors with much higher selectivity against huPA. While this latter property is desired, the sparing of the orthologue murine poses difficulties for the testing of the inhibitor in preclinical mouse model. In this work, we have applied a Darwinian evolution-based approach to identify phage-encoded bicyclic peptide inhibitors of huPA with better cross-reactivity towards murine uPA (muPA). The best selected bicyclic peptide (UK132) inhibited huPA and muPA with Ki values of 0.33 and 12.58 µM, respectively. The inhibition appears to be specific for uPA, as UK132 only weakly inhibits a panel of structurally similar serine proteases. Removal or substitution of the second loop with one not evolved in vitro led to monocyclic and bicyclic peptide analogues with lower potency than UK132. Moreover, swapping of 1,3,5-tris-(bromomethyl)-benzene with different small molecules not used in the phage selection, resulted in an 80-fold reduction of potency, revealing the important structural role of the branched cyclization linker. Further substitution of an arginine in UK132 to a lysine resulted in a bicyclic peptide UK140 with enhanced inhibitory potency against both huPA (Ki = 0.20 µM) and murine orthologue (Ki = 2.79 µM). By combining good specificity, nanomolar affinity and a low molecular mass, the bicyclic peptide inhibitor developed in this work may provide a novel human and murine cross-reactive lead for the development of a potent and selective anti-metastatic therapy.