Serum il-18 and rs187238 single nucleotide polymorphism are associated with high-density lipoprotein changes in covid-19 outpatients.

AIM: COVID-19 is an inflammatory disease and its prognosis is associated with cardiovascular risk, which can be associated with changes in lipoprotein metabolism. The single nucleotide polymorphism (SNP) rs187238 of Interleukin (IL)-18 is extensively reported in association with worsening inflammatory and cardiovascular disease (CVD). This study evaluated the association of IL-18 levels and its SNP rs187238 with lipoprotein profile changes in COVID-19 outpatients. METHODS: Observational, analytical, cross-sectional study that evaluated 250 patients with respiratory syndrome, 36% (n = 90) with COVID-19. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apolipoproteins A-I and B (Apo A-I and Apo B) and IL-18 levels were determined. Polymorphism genotyping was done by real-time polymerase chain reaction (qPCR). The significance level was p < 0.05. RESULTS: Patients with COVID-19 showed a reduction in TC and HDL-c, without difference in IL-18. HDL-c and LDL-c had a high frequency outside the reference values. There was a negative correlation of IL-18 with HDL-c and a positive correlation with Apo B/Apo A-I ratio. The frequencies of the C (wild) and G (polymorphic) alleles between patients with and without COVID-19 followed the Hardy-Weinberg equilibrium. However, COVID-19 was associated with reduced HDL-c and Apo A-I values in patients with the CC genotype. CONCLUSION: IL-18 levels and its SNP rs187238 were associated with decreased HDL-c and Apo A-I in COVID-19 outpatients.

Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo.

Resveratrol (RSV), a phytoalexin from grapes and peanuts, has been reported to exhibit antiproliferative effects on various cancer cell lines. In breast cancer, RSV has been demonstrated to exert an antiproliferative effect on both hormone-dependent and hormone-independent breast cancer cell lines. However, RSV is a lipophilic drug, and its therapeutic effect could be improved through nanoencapsulation. Functionalizing polymeric nanoparticles based on polycaprolactone (PCL) with polyethylene glycol 1000 tocopheryl succinate (TPGS) has been reported to prolong drug circulation and reduce drug resistance. However, the effect of TPGS on the physicochemical properties and biological effects of breast cancer cells remains unclear. Therefore, this study aimed to develop RSV-loaded PCL nanoparticles using nanoprecipitation and investigate the effect of TPGS on the nanoparticles' physicochemical characteristics (particle size, zeta potential, encapsulation efficiency, morphology, and release rate) and biological effects on the 4T1 breast cancer cell line (cytotoxicity and cell uptake), in vitro and in vivo. The optimized nanoparticles without TPGS had a size of 138.1 ± 1.8 nm, a polydispersity index (PDI) of 0.182 ± 0.01, a zeta potential of -2.42 ± 0.56 mV, and an encapsulation efficiency of 98.2 ± 0.87%, while nanoparticles with TPGS had a size of 127.5 ± 3.11 nm, PDI of 0.186 ± 0.01, zeta potential of -2.91 ± 0.90 mV, and an encapsulation efficiency of 98.40 ± 0.004%. Scanning electron microscopy revealed spherical nanoparticles with low aggregation tendency. Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) identified the constituents of the nanoparticles and the presence of drug encapsulation in an amorphous state. In vitro release studies showed that both formulations followed the same dissolution profiles, with no statistical differences. In cytotoxicity tests, IC50 values of 0.12 µM, 0.73 µM, and 4.06 µM were found for the formulation without TPGS, with TPGS, and pure drug, respectively, indicating the potentiation of the cytotoxic effect of resveratrol when encapsulated. Flow cytometry and confocal microscopy tests indicated excellent cellular uptake dependent on the concentration of nanoparticles, with a significant difference between the two formulations, suggesting that TPGS may pose a problem in the endocytosis of nanoparticles. The in vivo study evaluating the antitumor activity of the nanoparticles confirmed the data obtained in the in vitro tests, demonstrating that the nanoparticle without TPGS significantly reduced tumor volume, tumor mass, maintained body weight, and improved survival in mice. Moreover, the biochemical evaluation evidenced possible hepatotoxicity for formulation with TPGS.