A redox homeostasis disruptor based on a biodegradable nanoplatform for ultrasound (US) imaging-guided high-performance ferroptosis therapy of tumors.

The synergistic disruption of intracellular redox homeostasis through the combination of ferroptosis/gas therapy shows promise in enhancing the antitumor efficacy. However, the development of an optimal delivery system encounters significant challenges, including effective storage, precise delivery, and controlled release of therapeutic gas. In this study, we propose the utilization of a redox homeostasis disruptor that is selectively activated by the tumor microenvironment (TME), in conjunction with our newly developed nanoplatforms (MC@HMOS@Au@RGD), for highly efficient ferroptosis therapy of tumors. The TME-triggered degradation of HMOS initiates the release of MC and AuNPs from the MC@HMOS@Au@RGD nanoplatform. The released MC subsequently reacts with endogenous hydrogen peroxide (H2O2) and H+ to enable the on-demand release of CO gas, leading to mitochondrial damage. Simultaneously, the released AuNPs exhibit GOx-like activity, catalyzing glucose to generate gluconic acid and H2O2. This process not only promotes the decomposition of MnCO to enhance CO production but also enhances the Fenton-like reaction between Mn2+ and H2O2, generating ROS through the modulation of the H+ and H2O2-enriched TME. Moreover, the generation of CO bubbles enables the monitoring of the ferroptosis treatment process through ultrasound (US) imaging. The efficacy of our prepared MC@HMOS@Au@RGD disruptors in ferroptosis therapy is validated through both in vitro and in vivo experiments.

A strategy of disrupted redox homeostasis specifically initiated by the tumor microenvironment and our constructed MC@HMOS@Au@RGD nanoplatforms is proposed for ultrasound (US) imaging-guided potent ferroptosis therapy of tumors.

The association between marathon running and high-sensitivity cardiac troponin: A systematic review and meta-analysis.

BACKGROUND: Marathon running is an extreme sport with a distance of about 42 kilometers. Its relationship to high-sensitivity cardiac troponin (hs-cTn) remains controversial. OBJECTIVE: As the gold standard for detecting myocardial injury, the trends of hs-cTn before and after a marathon were investigated and analyzed. METHODS: A literature search was conducted in PubMed, EMBASE, and Cochrane Library databases by combing the keywords marathon and troponin, and studies regarding high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations before and after marathon running (not for half-marathon and ultra-marathon) were included. "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" were used to assess the risk of bias. Statistical analysis was performed using Review Manager, presenting data as mean values and 95% confidence intervals (CIs). Sensitivity analysis and subgroup analysis were performed if there was high heterogeneity among studies based on I2 statistic. RESULTS: A total of 13 studies involving 824 marathoners were included in this systematic review and meta-analysis. Both hs-cTnI (MD 68.79 ng/L, [95% CI 53.22, 84.37], p< 0.001) and hs-cTnT (MD 42.91 ng/L, [95% CI 30.39, 55.43], p< 0.001) were elevated after running a marathon, but the concentration of hs-cTnT returned to baseline after 72 to 96 h post-race (MD 0.11 ng/L, [95% CI -1.30, 1.52], p= 0.88). The results of subgroup analysis demonstrated that the 99th percentile upper reference limit of hs-cTnT might be the source of heterogeneity. CONCLUSION: The concentrations of hs-cTnI and hs-cTnT were increased after marathon running, but the change of hs-cTnT is usually not seen as irreversible myocardial injury.

Synthetic/natural blended polymer fibrous meshes composed of polylactide, gelatin and glycosaminoglycan for cartilage repair.

Electrospinning is a common and effective technology used for the fabrication of biomimetic nanofibers targeting tissue regeneration applications. As for cartilage regeneration, nanofibers containing natural components derived from cartilage extracellular matrix (ECM) are preferred. However, it is not easy an task to electrospin glycosaminoglycan (GAG) like hyaluronic acid (HA) and chondroitin sulfate (CS) by themselves. In this study, HA and/or CS were co-electrospun with poly(L-lactide) (PLLA) or PLLA/gelatin (1:1 in weight ratio) to obtain GAG-containing composite nanofibers. All the prepared composite nanofibers were non-cytotoxic, able to support cell attachment, spread and proliferation. In the differentiation studies, the PLLA/GAG and the PLLA/gelatin/GAG nanofibers demonstrated stronger capacities in promoting the chondrogenic differentiation of both the bone marrow mesenchymal stromal cells (BMSCs) and chondrocytes than the respective PLLA and PLLA/gelatin nanofibers, even in the proliferation medium without extra inductive factors. The incorporation of gelatin greatly improved the hydrophilicity of the fibrous meshes. At the meantime, the PLLA/gelatin/GAG nanofibers were more efficient than the PLLA/GAG nanofibers in enhancing the chondrogenic differentiation. It was found that the PLLA/gelatin/HA/CS (HA and CS in 1:1 weight ratio) nanofibers demonstrated a stronger synergetic effect on up-regulating chondrogenesis than both the PLLA/gelatin/HA and the PLLA/gelatin/CS nanofibers, when the GAG amounts in all the preparations were controlled as 3 wt.%. Herein, GAG-containing composite nanofibers were successfully electrospun and their potentials for cartilage repair were proved.