Characterization and pharmacokinetics of cinnamon and star anise compound essential oil pellets prepared via centrifugal granulation technology.

Cinnamon and star anise essential oils are extracted from natural plants and provide a theoretical basis for the development and clinical application of compound essential oil pellets. However, cinnamon oil and star anise oil have the characteristics of a pungent taste, extreme volatility, poor palatability, and unstable physical and chemical properties, which limit their clinical use in veterinary medicine. In this study, the inhibitory effects of cinnamon oil and star anise oil on Escherichia coli and Salmonella were measured. Compound essential oil pellets were successfully prepared by centrifugal granulation technology. Subsequently, the in vitro dissolution of the pellets and their pharmacokinetics in pigs were investigated. The results showd that, cinnamon and star anise oils showed synergistic or additive inhibitiory effects on Escherichia coli and Salmonella. The oil pellets had enteric characteristics in vitro and high dissolution in vitro. The pharmacokinetic results showed that the pharmacokinetic parameters Cmax and AUC were directly correlated with the dosage and showed linear pharmacokinetic characteristics, which provided a theoretical basis for the development and clinical application of compound essential oil pellets.

Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence.

Introduction: Diabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as the leading cause of death from end-stage renal disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting the onset and progression of chronic kidney disease (CKD) and acute kidney injuries. This study was designed to delve deeply into the pathological mechanisms between glomerulus-associated DN and cellular senescence. Methods: Glomerulus-associated DN datasets and cellular senescence-related genes were acquired from the Gene Expression Omnibus (GEO) and CellAge database respectively. By integrating bioinformatics and machine learning methodologies including the LASSO regression analysis and Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the selected genes. Rigorous experimental validations were subsequently conducted in the mouse model to corroborate the identification of three signature genes, namely LOX, FOXD1 and GJA1. Molecular docking with chlorogenic acids (CGA) was further established not only to validate LOX, FOXD1 and GJA1 as diagnostic markers but also reveal their potential therapeutic effects. Results and discussion: In conclusion, our findings pinpointed three diagnostic markers of glomerulus-associated DN on the basis of cellular senescence. These markers could not only predict an increased risk of DN progression but also present promising therapeutic targets, potentially ushering in innovative treatments for DN in the elderly population.

Preparation, Characterization and Pharmacokinetics of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles.

The clinical use of nonsteroidal anti-inflammatory drugs is limited by their poor water solubility, unstable absorption, and low bioavailability. Solid lipid nanoparticles (SLNs) exhibit high biocompatibility and the ability to improve the bioavailability of drugs with low water solubility. Therefore, in this study, a tolfenamic acid solid lipid nanoparticle (TA-SLN) suspension was prepared by a hot melt-emulsification ultrasonication method to improve the sustained release and bioavailability of TA. The encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), and zeta potential of the TA-SLN suspension were 82.50 ± 0.63%, 25.13 ± 0.28%, 492 ± 6.51 nm, 0.309 ± 0.02 and -21.7 ± 0.51 mV, respectively. The TA-SLN suspension was characterized by dynamic light scattering (DLS), fluorescence microscopy (FM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The TA-SLN suspension showed improved sustained drug release in vitro compared with the commercially available TA injection. After intramuscular administration to pigs (4 mg/kg), the TA-SLN suspension displayed increases in the pharmacokinetic parameters Tmax, T1/2, and MRT0-∞ by 4.39-, 3.78-, and 3.78-fold, respectively, compared with TA injection, and showed a relative bioavailability of 185.33%. Thus, this prepared solid lipid nanosuspension is a promising new formulation.

Gender-Disparities in the in-Hospital Clinical Outcome Among Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

PURPOSE: The current study was to evaluate the gender-disparities in the in-hospital thrombotic and bleeding events among patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Patients with CKD undergoing PCI were retrospectively enrolled. Baseline characteristics, and thrombotic and bleeding events occurred during hospitalization were collected and compared by gender. RESULTS: Compared to males (n = 558), females (n = 402) were older and more likely to have diabetes mellitus (37.1% vs 29.7%). Females had a lower estimated glomerular filtration rate (eGFR; 51.2 ± 7.9 vs 54.6 ± 5.1 mL/min/1.73m2) and were more likely to undergo urgent PCI (66.7% vs 60.2%) and use glycoprotein IIb/IIIa inhibitor (15.4% vs 7.5%) at peri-PCI period. Compared to males, females had a higher rate of in-hospital mortality which was due to thrombotic events (9.0% vs 3.4%). Females also had a higher rate of moderate-to-severe hemorrhage (8.0% vs 3.2%). After multivariable adjustment, diabetes mellitus (odds ratio [OR] 1.15 and 95% confidence interval [CI] 1.07-1.29) and acute coronary syndrome (ACS) presentation (OR 1.53 and 95% CI 1.34-1.93) were associated with gender-disparities in composite thrombotic events. Ageing (OR 1.10 and 95% CI 1.02-1.33), diabetes mellitus (OR 1.21 and 95% CI 1.07-1.40) and glycoprotein IIb/IIIa inhibitor use (OR 1.13 and 95% CI 1.02-1.28) were associated with composite bleeding events. CONCLUSION: Females with CKD undergoing PCI had a higher risk of experiencing in-hospital thrombotic and bleeding events than males.

MiR-133a is a potential target for arterial calcification in patients with end-stage renal disease.

BACKGROUND: Arterial calcification is an important risk factor for patients with end-stage renal disease. Despite substantial research efforts, the detailed mechanisms of the process of arterial calcification in end-stage renal disease remain unclear. METHODS: miR-133a expression in radial artery samples was detected by FISH and Alizarin Red Staining. The expressions of miR-133a and RUNX2 in A7r5 cells with BMP2 induction were detected by qRT-PCR. In addition, qRT-PCR, Western blot, and ELISA assay were performed to detect changes in miR-133a levels in A7R5 cells after different treatments. RESULTS: Alizarin Red staining showed that red crystal deposition occurred in the tunica media. FISH analysis indicated that miR-133a was upregulated in the tunica media of the radial artery samples without calcification when compared with those with calcification. We also found that expression of RUNX2 in A7r5 cells increased at day 7 and day 14 after BMP2 induction and decreased miR-133a expression decreased at day 14. In addition, RUNX2 protein and OCN expression were upregulated in A7r5 cells during BMP2-induced calcification. When miR-133a expression was suppressed, cell calcification aggravated, which led to upregulation of RUNX2 and OCN. When miR-133a was overexpressed, calcification of cells was inhibited, resulting in downregulation of RUNX2 and OCN. CONCLUSION: The present study reveals that miR-133a could indirectly regulate cell calcification through the RUNX2 gene expression. Our findings provide insight into the potential use of miR-133a as a molecular target for diagnosing vascular calcification in end-stage renal disease.