Development of an LC–MS/MS method for the quantitation of deoxyglycychloxazol in rat plasma and its application in pharmacokinetic study

Deoxyglycychloxazol （TY501） is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of methanol and 10 mM ammonium formate （containing 0.1% of formic acid） （90：10, v/v）. The selected reaction monitoring （SRM） transitions were performed at m/z 647.4→191.2 for TY501 and m/z 473.3→143.3 for astragaloside aglycone （IS） in the positive ion mode with atmospheric pressure chemical ionization （APCI） source. Calibration curve was linear over the concentration range of 5-5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra- and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within ± 1.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.

Leukocyte/platelet hybrid membrane-camouflaged dendritic large pore mesoporous silica nanoparticles co-loaded with photo/chemotherapeutic agents for triple negative breast cancer combination treatment

Triple-negative breast cancer(TNBC)is an aggressive subset of breast cancer and currently lacks effective therapeutic targets.As two main phototherapeutic methods,photothermal therapy(PTT)and photodynamic therapy(PDT)show many advantages in TNBC treatment,and their combination with chemotherapy can achieve synergistic therapeutic effects.In the present study,a biomimetic nanoplatform was developed based on leukocyte/platelet hybrid membrane(LPHM)and dendritic large pore mesoporous silicon nanoparticles(DLMSNs).A near infrared(NIR)fluorescent dye IR780 and a chemotherapeutic drug doxorubicin(DOX)were co-loaded into the large pores of DLMSNs to prepare DLMSN@DOX/IR780(DDI)nanoparticles(NPs),followed by camouflage with LPHM to obtain LPHM@DDI NPs.Through the mediation of LPHM,LPHM@DDI NPs showed an excellent TNBC-targeting ability and very high PTT/PDT performances in vitro and in vivo.Upon NIR laser irradiation,LPHM@DDI NPs exhibited synergistic cytotoxicity and apoptosis-inducing activity in TNBC cells,and effectively suppressed tumor growth and recurrence in TNBC mice through tumor ablation and anti-angiogenesis.These synergistic effects were sourced from the combination of PTT/PDT and chemotherapy.Altogether,this study offers a promising biomimetic nanoplatform for efficient co-loading and targeted delivery of photo/chemotherapeutic agents for TNBC combination treatment.

Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic urban Chinese popula- tion： a cross-section study

The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose （FPG） levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects （1027 men, and 2433 women, aged 35-75 years old） who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose （IFG） was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels （lowest tertiles, FPG： 5.376 ± 0.018; middle tertiles, 5.324± 0.018; highest tertiles, 5.276±0.018mmol/L; P = 0.001）. Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level （OR： 1.75; 95% CI： 1.20-2.56）. In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.

MicroRNA-21 in the pathogenesis of acute kidney injury

Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or death.Therefore,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat AKI.However,the mech-anisms modulating the pathogenesis of AKI still remain largely undetermined.MicroRNAs(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expres-sion.MicroRNA-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in AKI.As a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing AKI.This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.