Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.

Objective. To investigate the anthropometric indicators that can effectively predict the nonalcoholic fatty liver disease (NAFLD). Methods. The height, body weight, waist and hip circumference were measured, and body mass index (BMI), waist-to-height (WHtR) and waist-to-hip ratio (WHR) were calculated. M-H chi square test, logistic regression analysis, and receiver-operating characteristic (ROC) curve were employed for the analysis of risk factors. Patients or Materials. 490 patients were recruited, of whom 250 were diagnosed as NAFLD and 240 as non-NAFLD (control group). Results. Compared with the control group, the BMI, WHR, and WHtR were significantly higher in patients with NAFLD. Logistic regression analysis showed that BMI and WHR were effective prognostic factors of NAFLD. In addition, WHR plays a more important role in prediction of NAFLD by the area under curve. Conclusion. WHR is closely related to the occurrence of NAFLD. We assume that WHR is beneficial for the diagnosis NAFLD.

Folate receptors (FRs) have been identified as cellular surface markers for cancer and leukemia. Liposomes containing lipophilic derivatives of folate have been shown to effectively target FRexpressing cells. Here, we report the synthesis of a novel lipophilic folate derivative, folatepolyethylene glycol-cholesterol hemisuccinate (F-PEG-CHEMS), and its evaluation as a targeting ligand for liposomal doxorubicin (L-DOX) in FR-expressing cells. Liposomes containing F-PEG-CHEMS, with a mean diameter of 120±20nm, were synthesized by polycarbonate membrane extrusion and were shown to have excellent colloidal stability. The liposomes were taken up selectively by KB cells, which overexpress FR-α. Compared to folate-PEG-cholesterol (F-PEGChol), which contains a carbamate linkage, F-PEG-CHEMS better retained its FR-targeting activity during prolonged storage. In addition, F-PEG-CHEMS containing liposomes loaded with DOX (F-L-DOX) showed greater cytotoxicity (IC 50 =10.0μM) than non-targeted control L-DOX (IC 50 = 57.5μM) in KB cells. In ICR mice, both targeted and non-targeted liposomes exhibited long circulation properties, although F-L-DOX (t 1/2 = 12.34 hr) showed more rapid plasma clearance than L-DOX (t 1/2 = 17.10 hr). These results suggest that F-PEG-CHEMS is effective as a novel ligand for the synthesis of FR-targeted liposomes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , 2001; Momot et al., 2003;Papahadjopoulos et al., 1991) and is facilitated by plasma protein opsonization. Incorporation of polyethylene glycol (PEG) coating on liposomes has been shown to reduce the rate of RES clearance of liposomes Fritze et al., 2006; Momot et al., 2003;Papahadjopoulos et al., 1991). Liposomal delivery has been shown to reduce cardiac toxicity of doxorubicin (Perez et al., 2002). Targeted liposomes can be synthesized by incorporating a tumor cell-selective ligand, such as antibodies, transferrin and folic acid (Gabizon et al., 2004;Lukyanov et al., 2004;Pan et al. 2007;Wu et al., 2006a;Xiong et al., 2005), via a lipophilic anchor, typically consisting of a derivative of distearoylphosphatidylethanolamine (DSPE). NIH Public AccessMembrane folate receptors (FRs), including FR-α and FR-β, are glycosylphosphatidylinositol (GPI)-anchored glycoproteins. FR-α expression is amplified in over 90% of ovarian carcinomas and at varying frequencies in other epithelial cancers. Meanwhile, FR-β is expressed in a non-functional form in neutrophils and in a functional form in activated macrophages and in myeloid leukemias (Elwood et al., 1989;McHugh et al., 1979). In contrast, most normal...

Rifapentine (RPT) is an antituberculosis drug that may shorten treatment duration when substituted for rifampin (RIF). The maximal tolerated daily dose of RPT and its potential for cytochrome 3A4 induction and autoinduction at clinically relevant doses are unknown. In this phase I, dose-escalation study among healthy volunteers, daily doses as high as a prespecified maximum of 20 mg/kg/day were well tolerated. Steady-state RPT concentrations increased with dose from 5 to 15 mg/kg, but area under the plasma concentration–time curve (AUC0–24) and maximum concentration (Cmax) were similar in the 15- and 20-mg/kg cohorts. Although RPT pharmacokinetics (PK) appeared to be time-dependent, accumulation occurred with daily dosing. The mean AUC0–12 of oral midazolam (MDZ), a cytochrome 3A (CYP3A) probe drug, was reduced by 93% with the coadministration of RPT and by 74% with the coadministration of RIF (P < 0.01). Changes in the oral clearance of MDZ did not vary by RPT dose. In conclusion, RPT was tolerated at doses as high as 20 mg/kg/day, its PK were less than dose-proportional, and its CYP3A induction was robust.

No abstract

AimsThe aims of this study were to assess the effectiveness of self-efficacy-focused education on health outcomes in persons with diabetes and review the strategies employed in the interventions.BackgroundThe traditional educational interventions for persons with diabetes were insufficient to achieve the desired outcomes. Self-efficacy-focused education has been used to regulate the blood sugar level, behaviors, and psychosocial indicators for persons with diabetes.DesignThis study is a systematic review and meta-analysis.MethodsStudies on the effectiveness of self-efficacy-focused education in persons with diabetes were searched in six databases from inception until January 2018. The data were extracted and the quality of literature was assessed independently. Review Manager 5.3 was applied for the meta-analysis. Besides, the findings were summarized for narrative synthesis.ResultsSixteen trials with 1,745 participants were included in the systematic review and ten trails with 1,308 participants in the meta-analysis. The meta-analysis for A1C, self-efficacy, self-management behaviors, knowledge, and quality of life (QOL) were represented in four, six, six, three, and three studies, respectively. The findings indicated that self-efficacy-focused education would probably reduce A1C, enhance self-efficacy, regulate self-management behaviors, increase knowledge, and improve the QOL for patients with diabetes. Weak quality studies, limited participants, and heterogeneity hindered the results pooled of the other secondary outcomes of fasting blood glucose, 2-hour plasma glucose, weight, weight circumference, body mass index, plasma lipid profile, and other psychological indicators. Goal setting, self-management skills practicing and recording, peer models, demonstration, persuasion by health providers, and positive feedback were the most commonly used strategies in the interventions. However, physiological/emotion arousal strategies were relatively less applied and varied significantly.ConclusionIndividuals with diabetes may benefit a lot from the self-efficacy-focused education. However, insufficient high-quality studies, short-term follow-up period, relatively deficient physiological/emotion strategies, and incomplete outcome assessments were the drawbacks in most studies. Establishing satisfactory self-efficacy-focused education and better evaluating the effects were required in further studies.

Glucose-conjugated malonato-platinum(II) complexes are designed and synthesized to target tumor-specific active transporters, namely, glucose transporters (GLUTs); the complexes exhibit much higher aqueous solubility by 150 times, improved potency in cytotoxicities by 10 times, and increased therapeutic index by over 30 fold compared to the newest generation of clinical drugs oxaliplatin.

Catalytic enantioselective halocyclization of 2-alkenylphenols and enamides have been achieved through the use of chiral amidophosphate catalysts and halo-Lewis acids. Density functional theory calculations suggested that the Lewis basicity of the catalyst played an important role in the reactivity and enantioselectivity. The resulting chiral halogenated chromans can be transformed to α-Tocopherol, α-Tocotrienol, Daedalin A and Englitazone in short steps. Furthermore, a halogenated product with an unsaturated side chain may provide polycyclic adducts under radical cyclization conditions.