The association of platelet count, high-density lipoprotein cholesterol, and platelet/high-density lipoprotein cholesterol ratio with serum soluble Klotho.

BACKGROUND AND OBJECTIVE: Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. METHODS: Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. RESULTS: A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (ß: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (ß: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations. CONCLUSIONS: Both the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration.

Unveiling a pH-Responsive Dual-Androgen-Blocking Magnetic Molecularly Imprinted Polymer for Enhanced Synergistic Therapy of Prostate Cancer.

Prostate cancer is the most common malignancy diagnosed in men. Androgens are directly related to its pathogenesis. Inhibition of the androgen receptor (AR) is considered to be the most promising therapeutic approach for the treatment of prostate cancer. In this study, a new type of pH-responsive dual androgen-blocking nanodrug (FASC MIPs) based on a molecularly imprinted polymer has been designed and synthesized. The nanodrug could selectively sequester testosterone from the prostate tumor through specific molecular imprinting sites and simultaneously deliver the AR inhibitory drug bicalutamide, which ultimately leads to enhanced synergistic therapy of prostate cancer. FASC MIPs demonstrate excellent pH responsiveness in a simulated tumor microenvironment due to the presence of chitosan and significantly inhibit the growth of prostate cancer cells (LNCaP cells) by blocking the G1 phase of cytokinesis. Additionally, the nanodrug also displayed excellent antitumor properties in a xenograft mouse model of prostate cancer without any sign of detrimental effects on healthy tissues and organs. Both in vitro and in vivo studies verified the augmented and synergistic therapeutic effects of FASC MIPs, and the proposed dual-androgen-blocking strategy could explore novel avenues in prostate cancer treatment.