Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling / 老年心脏病学杂志（英文版）

BACKGROUND@#Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.@*METHODS@#In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.@*RESULTS@#The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.@*CONCLUSIONS@#These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Effect of antiplatelet pretreatment on platelet aggregation and clinical outcomes in acute ischemic stroke patients treated with recombinant tissue-type plasminogen activator.

Early administration of antiplatelet agents in acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) is a potential therapeutic strategy, however, safety and efficacy are not well established. We hypothesize that antiplatelet pretreatment (AP) before IVT have a similarly role as initiation of AP within the first 24 hours following IVT. We aimed to explore the effect of AP on platelet aggregation and clinical outcomes in thrombolysis-treated AIS patients. We enrolled AIS patients treated with IVT at the Neurology Department of the Nanjing First Hospital from January 2016 to June 2018. Prior use of antiplatelet agent was recorded. Light transmittance aggregometry was used to estimate the maximum platelet aggregation (MPA). Linear regression model was performed to investigate the factors associated with MPA. Multivariate logistic regression was used to analyse the association between AP and clinical outcomes. A total of 59 patients were included; 23 (38.9 %) were taking antiplatelet agent before stroke. Prior AP (ß = -20.209, SE mean=6.574; P=0.004) was significantly lower the arachidonic acid-induced MPA at the time point of 3h after thrombolysis. AP did not increase of the risk for sICH (OR=3.41, 95%CI 0.16-7.20, p=0.436) or mortality (OR=3.55, 95%CI 0.39-8.52, p=0.260). There were no associations between AP and improved clinical outcomes (all P>0.05). In thrombolysis-treated AIS patients, AP was associated with lower MPA after thrombolysis. AP is safe in these patients, however, further studies are required to confirm the efficacy.

Plasma Protein Binding Characteristics of Neopanaxadiol in Rats by UPLC-MS/MS / 中国药学杂志

OBJECTIVE: To develop an UPLC-MS/MS method for the determination of neopanaxadiol(NPD) in rat plasma sample, and to investigate plasma protein binding rate of NPD in rats. METHODS: Under three different concentrations, equilibrium dialysis method was utilized to imitate the binding process between NPD and plasma protein. The concentration of NPD in and out of the dialysis membrane was determined by UPLC-MS/MS and the plasma protein binding rate of NPD were calculated. RESULTS: Excellent linearity was found between 0.05-8 μg·mL -1. Intra- and inter-day precision values (RSD) of QC samples were both below 15% and the extraction recoveries of NPD from biological matrices were better than 79.37%. The plasma protein binding rates of NPD were (86.55±4.50)%, (76.50±2.61)% and (78.25±1.32)% at low, middle and high concentrations, respectively. There was no significant difference among three concentrations. CONCLUSION: These results indicate the high plasma protein binding rates of NPD in plasma in combination mode.

Occlusion of dentinal tubules using tricalcium silicate / 中国组织工程研究

BACKGROUND:A number of in vitro experiments have confirmed that the tricalcium silicate not only can be closely integrated with the dentin through self-curing process, but also can induce dentin remineralization in the physiological environment, thereby effectively blocking the dentinal tubules. OBJECTIVE:To further verify the effects of tricalcium silicate solution on the occlusion of dentinal tubules. METHODS:Thirty-six dentinal discs were made of free first premolars from orthodontic patients, and divided into three pretreatment groups randomly. The teeth were soaked in pretreatment solution for 2 minutes, namely 0.29 mol/L ethylene diamine tetraacetie acid, 6%citric acid, and rinsed ultrasonical y with deionized water 20 minutes, respectively. Every above-mentioned group was randomly assigned into experimental group (tricalcium silicate), control group (sodium fluoride) and blank group, and corresponding materials in each group were used to coat the outer dentinal tubules (2 minutes/time). Then, the dentinal discs were saved in artificial saliva in a 37 observed using scanning electron microscope. Diameter and area of open dentinal tubules were calculated. RESULTS AND CONCLUSION:After pretreatment, the dentinal tubules were at open state;except for the blank control group to maintain the original state, acid etching and ethylene diamine tetraacetie acid pretreatment solutions had a stronger capacity of demineralization, which led to the dentinal tubules open. After the dentinal tubules were treated with sodium fluoride and tricalcium silicate, there were varying degrees of sediments, and open dentinal tubule area and average diameter in the sodium fluoride and tricalcium silicate groups were lower than those in the control group (P<0.05). The dentinal tubule treated with tricalcium silicate was almost entirely closed homogeneously, and occasional y, a single open dentinal tubule was seen. Open dentinal tubule area and average diameter in the tricalcium silicate group were significantly lower than those in the sodium fluoride group (P<0.05). The findings verify that dentin occlusion using tricalcium silicate is superior to that using sodium fluoride;and dentin tubule pretreatment with acid etching or ethylene diamine tetraacetie acid is beneficial to desensitization effects.

Urine excretion of neopanaxadiol in rats by UPLC-MS/MS / 中国药学杂志

OBJECTIVE: To develop a UPLC-MS/MS method for the determination of neopanaxadiol (NPD) in rat urine samples, and to explore the excretion patterns of NPD in rats after oral administration. METHODS: NPD was extracted from u-rine samples by liquid-liquid extraction. The concentration of NPD in urine was determined by UPLC-MS/MS and the cumulative excretion amount and excretion rate of NPD were calculated after a single oral administration of NPD at 100 mg · kg-1 to SD rats. RESULTS: Excellent linearity was found between 80-1280 ng · mL-1. The intra-and inter-day RSDs of the QC samples were both below 15% and the extraction recoveries of NPD were higher than 80%. The cumulative excretion of unchanged NPD in urine within 96 h amounted to (0.0233±0.0356)% of the dose. CONCLUSION: NPD is hardly eliminated through urine within 96 h in rats.