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Kokusaginine is a bioactive ingredient extracted from Ruta graveolens L., which has a range of biological activities. Its pharmacokinetic (PK) properties are particularly important for clinical applications; however, they have not been fully elucidated. In addition, the effect of sex differences on drug metabolism is increasingly being recognized, but most studies have ignored this important factor. This study aims to fill this knowledge gap by taking an in-depth look at the PK properties of kokusaginine and how gender affects its metabolism and distribution in the body. It also lays the foundation for clinical drug development. In this study, a sensitive ultra-high-performance liquid chromatography (UPLC) method was developed and validated for quantifying kokusaginine in Sprague Dawley (SD) rat plasma and tissue homogenates. Metabolic stability was evaluated in vitro using gender-specific liver microsomes. Innovatively, we incorporated sex as a variable into both in vitro and in vivo PK studies in SD rats, analyzing key parameters with Phoenix 8.3.5 software. The developed UPLC method demonstrated high sensitivity and precision, essential for PK analysis. Notably, in vitro studies revealed a pronounced sex-dependent metabolic variability (p < 0.05). In vivo, gender significantly affected the Area Under the Moment Curve (AUMC)(0-∞) of the plasma PK parameter (p < 0.05) and the AUMC(0-t) of brain tissue (p < 0.0001), underscoring the necessity of sex-specific PK assessments. The calculated absolute bioavailability of 71.13 ± 12.75% confirmed the favorable oral absorption of kokusaginine. Additionally, our innovative tissue-plasma partition coefficient (Kp) analysis highlighted a rapid and uniform tissue distribution pattern. This study presents a sex-inclusive PK evaluation of kokusaginine, offering novel insights into its metabolic profile and distribution. These findings are instrumental for informing clinical medication practices, dosage optimization, and a nuanced understanding of drug efficacy and safety in a sex-specific context. [ABSTRACT FROM AUTHOR]

Coupling the San Diego gas phase reaction mechanism and the Moss Brookes soot model using FLUENT14.0 software, the effect of adding H2/CO on the fuel side on soot formation in an ethylene/air laminar diffusion flame was studied. A specific analysis was conducted on the effects of H2, CO and its chemical effects on flame temperature, soot volume fraction, mole fractions of important intermediate products OH, H, and C2H2, as well as rate of soot mass nucleation, surface growth, and oxidation. In the numerical calculation, the virtual substances FH2 and FCO are set to separate the chemical effect of H2 and CO and to analyze the chemical effect of adding H2 and CO on soot formation. The results show that the flame temperature increases slightly, and the soot volume fraction decreases monotonically with adding H2 and CO. The chemical effect of H2 increases the temperature, the mole fraction of C2H2 and H, the soot nucleation rate, and the surface growth rate, and finally, it promotes soot formation. The chemical effect of CO increases the temperature and H mole fraction, reduces the OH mole fraction, and then increases the soot surface growth rate and reduces the soot oxidation rate. The higher soot nucleation, surface growth rate, and lower oxidation rate jointly promote soot formation. [ABSTRACT FROM AUTHOR]

Abstract.: It has been known that oxidative stress plays an important role in the development of diabetic nephropathy (DN). The antioxidative effects of Astragalus saponin I (AS I) were studied in vitro and in vivo. In the presence of high glucose and H2O2, the total antioxidative capability, catalase, reduced glutathione, and superoxide dismutase level of rat mesangial cells were significantly decreased, and transforming growth factor β1 (TGF-β1) mRNA level, collagen IV, and laminin level were significantly increased. When compared with those in the high glucose group, these 4 indexes of cells incubated in 2.0 and/or 20 µmol/L of AS I were significantly enhanced, and levels of TGF-β1 mRNA, collagen IV and laminin were statistically decreased. By flowcytomery, percentages of S phase of cells incubated in high glucose and H2O2 were lowered, while those in AS I were increased. Furthermore, the physical behaviors of rats treated with 12 mg/kg of AS I restored with vigor and weight gaining, while the level of HbAlC was significantly reduced. Thus, AS I has antioxidative effects and is a potential compound worth further study because it may prevent the development of DN. Keywords:: Astragalus saponin I, diabetic nephropathy, antioxidative, mesangial cell

Objective: To investigate the value of the combined application of intravoxel incoherent motion (IVIM) and enhanced T2*-weighted angiography (ESWAN) for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC)., Materials and Methods: 76 patients with pathologically confirmed HCC were retrospectively enrolled and divided into the MVI-positive group (n=26) and MVI-negative group (n=50). Conventional MRI, IVIM, and ESWAN sequences were performed. Three region of interests (ROIs) were placed on the maximum axial slice of the lesion on D, D*, and f maps derived from IVIM sequence, and R2* map derived from ESWAN sequence, and intratumoral susceptibility signal (ITSS) from the phase map derived from ESWAN sequence was also automatically measured. Receiver operating characteristic (ROC) curves were drawn to evaluate the ability for predicting MVI. Univariate and multivariate logistic regression were used to screen independent risk predictors in clinical and imaging information. The Delong's test was used to compare the differences between the area under curves (AUCs)., Results: The D and D* values of MVI-negative group were significantly higher than those of MVI-positive group ( P =0.038, and P =0.023), which in MVI-negative group were 0.892×10 -3 (0.760×10 -3 , 1.303×10 -3 ) mm 2 /s and 0.055 (0.025, 0.100) mm 2 /s, and in MVI-positive group were 0.591×10 -3 (0.372×10 -3 , 0.824×10 -3 ) mm 2 /s and 0.028 (0.006, 0.050)mm 2 /s, respectively. The R2* and ITSS values of MVI-negative group were significantly lower than those of MVI-positive group ( P =0.034, and P =0.005), which in MVI-negative group were 29.290 (23.117, 35.228) Hz and 0.146 (0.086, 0.236), and in MVI-positive group were 43.696 (34.914, 58.083) Hz and 0.199 (0.155, 0.245), respectively. After univariate and multivariate analyses, only AFP (odds ratio, 0.183; 95% CI, 0.041-0.823; P = 0.027) was the independent risk factor for predicting the status of MVI. The AUCs of AFP, D, D*, R2*, and ITSS for prediction of MVI were 0.652, 0.739, 0.707, 0.798, and 0.657, respectively. The AUCs of IVIM (D+D*), ESWAN (R2*+ITSS), and combination (D+D*+R2*+ITSS) for predicting MVI were 0.772, 0.800, and, 0.855, respectively. When IVIM combined with ESWAN, the performance was improved with a sensitivity of 73.1% and a specificity of 92.0% (cut-off value: 0.502) and the AUC was significantly higher than AFP ( P =0.001), D ( P =0.038), D* ( P =0.023), R2* ( P =0.034), and ITSS ( P =0.005)., Conclusion: The IVIM and ESWAN parameters showed good efficacy in prediction of MVI in patients with HCC. The combination of IVIM and ESWAN may be useful for noninvasive prediction of MVI before clinical operation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Zhao, Wang, Liu, Zhang, Zhuang, Wang, Wang, Zhang, Song and Liu.)

Neurofibromatosis-Noonan syndrome (NFNS), a rare autosomal-dominant hereditary disease, is characterized by clinical manifestations of both neurofibromatosis type 1 ( NF1 ) and NS. We present a case of NFNS with short stature caused by a heterozygous nonsense variant of the NF1 gene. A 12-year-old boy was admitted because of short stature, numerous café-au-lait spots, low-set and posteriorly rotated ears, sparse eyebrows, broad forehead, and inverted triangular face. Cranial and spinal magnetic resonance imaging showed abnormal nodular lesions. Molecular analysis revealed a novel heterozygous c.6189 C > G (p.(Tyr2063*)) variant in the NF1 gene. The patient was not prescribed recombinant growth hormone (GH) therapy because exogenous GH may have enlarged the abnormal skeletal lesions. During follow-up, Lisch nodules were found in the ophthalmologic examination. NFNS, a variant form of NF1 , is caused by heterozygous mutations in the NF1 gene. The mechanism of GH deficiency caused by NF1 is still unclear. Whether NFNS patients should be treated with exogenous GH remains controversial., Competing Interests: Conflict of interest: None declared, (©Copyright 2023 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)