D. Medical Industries is a publicly traded holding company, headquartered in Israel, that develops and markets insulin pumps and infusion sets through its subsidiary, Spring-Set Health Solutions. Shares of the company are traded on the Tel Aviv Stock Exchange.D.
The application of medical magnesium (Mg) alloys in implantable medical devices is promising due to the similar modulus of elasticity and biodegradability to human bone, which facilitates osseointegration. However, rapid degradation and loss of mechanical strength remain critical issues. To tackle these challenges, in this study, liquid metal gallium (Ga), which possesses non-toxicity, excellent biocompatibility, moderate chemical reactivity, and superior alloying capability, was used to develop a novel Mg alloy coating that can simultaneously enhance mechanical strength, reduce the degradation rate, and provide antibacterial and osteogenic properties. A unique, simplified coating process applied liquid Ga to the surface of ZK60 Mg alloy, and coatings of varying thicknesses were successfully fabricated. The phase composition of the Mg-Ga alloy layers was identified mainly consisting of Ga5Mg2 and Ga2Mg. Vitro corrosion tests demonstrated that surface alloying of Ga with ZK60 effectively suppressed the degradation rate of the Mg alloy. Prolonged Mg-Ga alloying time improved human bone marrow mesenchymal stem cells (hBMSCs) adhesion, spreading, proliferation, and differentiation. The Mg-Ga alloy layer positively affected the early differentiation of osteoblasts and extracellular matrix mineralization, upregulating the expression of osteogenic-related genes and inhibiting osteoclast activity. Additionally, the Mg-Ga alloy exhibited excellent antibacterial properties through a combined effect of ion release and the formation of an alkaline environment. In short, the Ga-coated ZK60 Mg alloy demonstrated superior corrosion resistance, structural stability, cellular compatibility, osteogenic performance, and antibacterial capability, providing strong support for applying Mg alloys in medical implants.
Purpose:Ciprofol, a novel intravenous anaesthetic, is an analogue of propofol with superior anaesthetic efficacy. Ciprofol is widely metabolized in humans, and cytochrome P450 enzymes (CYPs) are involved in its metabolism. However, the drug‒drug interactions between ciprofol and drugs that may affect CYPs remains unclear. Therefore, we investigated the effects of voriconazole on the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of ciprofol. Methods:A randomized, two-period, two-sequence, crossover study was conducted in healthy participants who received a single intravenous dose of 0.4 mg/kg ciprofol (treatment A) and 0.4 mg/kg ciprofol after multiple doses of voriconazole (treatment B), a multiple inhibitor of CYP3A4/5, CYP2B6 and CYP2C9/19, in either sequence AB or sequence BA. Results:MOAA/S-time curves revealed that the participants were anaesthetized rapidly (2.01 min versus 1.82 min) and recovered smoothly (11.58 min versus 11.64 min) after receiving ciprofol either alone or combined with voriconazole. The mean BISpeak values were 41.1 and 44.4, respectively. Voriconazole slightly increased the plasma AUC of ciprofol, but the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for Cmax, AUC0-t and AUC0-∞ of plasma ciprofol were still in the range of 80%-125%, which demonstrated pharmacokinetic bioequivalence between the two treatments. No serious adverse effects were reported. Conclusion:Ciprofol was well tolerated in combination with voriconazole, and the anaesthetic effect was satisfactory. The dose of ciprofol is suggested not be adjusted in patients receiving the CYP inhibitor voriconazole based on the PK, PD and safety characteristics. Trial Registration:Clinicaltrials.gov, NCT04145583, registered on 25 October 2019.
Background The clinical treatment of Osteosarcoma (OS) faces major barriers due to the risk of tumor recurrence. Immunotherapy utilizing immune checkpoint blockade (ICB) antibodies has exhibited promise in inducing tumor rejection and providing clinical benefits for patients among various tumor types. However, tumors often develop resistance to immune rejection. Given the limitations of current therapies, there is an urgent need to explore novel therapeutic strategies to enhance anti-tumor immunity and prevent recurrence. This study aims to investigate the potential of α2-adrenergic receptor (α2-AR) agonists, delivered via a thermo-sensitive hydrogel (PLGA-PEG-PLGA), as a therapeutic strategy to combat immune rejection and tumor recurrence in osteosarcoma. Methods In this study, we investigated the anti-tumor effects of α2-AR agonists using a thermo-sensitive PLGA-PEG-PLGA hydrogel as a drug delivery system. The hydrogel was loaded with the α2-AR agonist UK14,304 and evaluated for its efficacy and biosafety in vitro and in vivo. In vitro experiments included cell viability assays (CCK-8), scratch wound healing assays, and Transwell assays to assess the impact of UK14,304 on OS cell lines. For in vivo studies, a subcutaneous OS xenograft mouse model was established using BALB/c nude and immunocompetent BALB/c mice. Tumor recurrence and growth were monitored after surgical resection and treatment with the hydrogel-agonist formulation. Proteomic analysis of tumor immune microenvironment (TME), Metascape, STRING, Cytoscape, TCGA and GTEx databases were performed to elucidate the underlying mechanisms of the anti-tumor effects. Results We evaluated the anti-tumor effects of α2-AR agonists (specifically UK14,304) loaded into a thermo-sensitive PLGA-PEG-PLGA hydrogel both in vitro and in vivo. In vitro experiments using OS cell lines (K7M2, 143b, and Khos) showed that UK14,304 did not significantly affect cell viability, migration, or invasion, indicating minimal direct cytotoxicity. In vivo studies using immunocompetent BALB/c mice demonstrated a significant reduction in tumor recurrence and growth when treated with UK14,304-loaded hydrogels compared to controls, highlighting an immune-mediated anti-tumor effect. Proteomic analysis of TME revealed that the anti-tumor mechanism involves the activation of CD8+ T cells and TCR signaling pathways, with ITGAL identified as a central regulatory factor. Additionally, bioinformatics analysis suggested the involvement of LLPS in enhancing TCR signaling. Correlation analysis with TCGA and GTEx databases further indicated that the identified proteins (e.g., MSN, TOLLIP, ITGAL) are associated with improved clinical outcomes. Conclusion Overall, our results demonstrate that α2-AR agonists may serve as a potential drug for a prospective drug delivery system in the post-surgical management of OS. Significance statement This study highlights the therapeutic efficacy of α2-AR agonists in osteosarcoma treatment through a novel drug delivery system, suggesting their potential to enhance anti-tumor immune responses by modulating CD8+ T cell activity and TCR signaling, as supported by correlations with clinical outcomes in TCGA and GTEx databases. The translational potential of this article The findings of this study present a promising translational potential by demonstrating the efficacy of α2-AR agonists in enhancing anti-tumor immunity in OS, potentially paving the way for targeted immunotherapies in post-surgical management to combat tumor recurrence and resistance.
Purpose: Next-generation sequencing (NGS) has transformed molecular diagnostics and precision oncology by enabling broad genomic profiling and informed treatment selection for non-small cell lung cancer (NSCLC). However, adoption in Southeast Asia remains limited, particularly in public healthcare settings. This study aimed to assess the landscape of NGS testing for NSCLC in Malaysia, identify barriers, and explore strategies clinicians use to improve patient access. Patients and Methods: A descriptive, cross-sectional survey comprising 18 questions was distributed to clinical oncologists and respiratory physicians across Malaysia over an eight-week period. The survey collected data on clinical experience with NGS, testing practices, perceived barriers, and access strategies. Descriptive statistics were used for analysis, and associations between healthcare sectors (public vs private) and NGS usage frequency were evaluated using the Chi-square test. Results: Seventy-one clinicians participated-67.6% clinical oncologists and 32.4% respiratory physicians. Private hospitals had the highest NGS uptake (38.5% testing all NSCLC patients), with the lowest in Ministry of Health (MoH) institutions (8.3%) (p<0.0001). Among oncologists, 45.8% used NGS for all or nearly all patients. For respiratory physicians, 35.3%, mainly from MoH, used it most of the time. NGS results were more frequently available in private referrals. Most private clinicians (84.6%) rated NGS accessibility as excellent. Key barriers included cost of testing and therapies, limited availability, long turnaround times, insufficient tissue, and unclear guidelines. Strategies to improve access included industry-subsidized programs, insurance coverage, and clinical trial enrolment. Conclusion: NGS adoption for NSCLC in Malaysia varies significantly across healthcare settings. Public hospitals face substantial barriers, particularly related to cost and access to testing and therapies. Addressing these challenges will require coordinated efforts across policy, infrastructure, clinician training, and public-private partnerships. This study offers key insights into the Malaysian NGS landscape and supports broader access to precision oncology.
