Retracted: Icariin inhibits proliferation,migration, and invasion of medulloblastoma DAOY cells by regulation of SPARC

Icariin (ICA) is obtained from Epimedium brevicornu maxim and exploited to remedy miscellaneous cancers. But the role of ICA in medulloblastoma remains hazy. The research delved into the antitumor activity of ICA in medulloblastoma DAOY cells. ICA with diverse concentrations was utilized to stimulate DAOY cells, and the biological functions of ICA in medulloblastoma DAOY cells were examined. Then, the relative SPARC expression was determined in ICA‐managed DAOY cells, and the pc‐SPARC vector was transfected into DAOY cells to further probe the influence of SPARC and JAK1/STAT3 and PI3K/AKT pathways in ICA‐managed DAOY cells. A xenograft model was established to investigate the function of ICA in vivo. ICA restrained cell viability, expedited apoptosis, prohibited cell migration and invasion, and meanwhile affected the associative factors expression in DAOY cells. Additionally, SPARC expression was declined in ICA‐stimulated DAOY cells. Overexpressed SPARC reversed the functions of ICA in above‐involved cell behaviors of DAYO cells and the correlative protein levels. Besides, ICA notably frustrated JAK1/STAT3 and PI3K/AKT activations in DAOY cells. Beyond that, ICA prohibited tumor formation in vivo. The results concluded that ICA exhibited the antitumor activity in DAOY cells via decreasing SPARC and inactivating JAK1/STAT3 and PI3K/AKT pathways.     

Golgi apparatus-synthesized sulfated glycosaminoglycans mediate polymerization and activation of the cGAMP sensor STING

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Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.     

The Influence of In Vivo Metabolic Modifications on ADMET Properties of Green Tea Catechins–In Silico Analysis

The health effects of green tea are associated with catechins: (?)-epigallocatechin-3-O-gallate (EGCG), (?)-epigallocatechin, (?)-epicatechin-3-O-gallate, and (?)-epicatechin. An understanding of compound absorption, distribution, metabolism, excretion, and toxicity characteristics is essential for explaining its biological activities. Herein, absorption, distribution, metabolism, excretion, and toxicity properties of in vivo detected metabolites of green tea catechins (GTCs) have been analyzed in silico. The influence of metabolic transformations on absorption, distribution, metabolism, and excretion profiles of GTCs corresponds to the effects of size, charge, and lipophilicity, as already observed for other small molecules. Mutagenic, carcinogenic, or liver toxic effects were predicted only for a few metabolites. Similar to galloylated GTCs EGCG and (--)-epicatechin-3-O-gallate, the sulfo-conjugates were predicted to bind at the warfarin binding site. The low free plasma concentration of these derivatives may be consequential to their serum albumin binding. The activity cliff detected for methylated conjugates of EGCG indicates that GTCs' pro-oxidative activity in bound state comes primarily from free hydroxyl groups of the pyrogallol ring B.     

Delivery of radix ophiopogonis polysaccharide via sucrose acetate isobutyrate-based in situ forming systems alone or combined with its mono-PEGylation

This work aimed to achieve long-lasting delivery of radix ophiopogonis polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the ‘90%SAIB/10% solvent’ system was used, the mean residence time (MRT) of ROP was prolonged by 4.3 5?～?7.00 times and the initial release rate was reduced significantly. However, this system was only suitable for days-long sustained release of ROP in short-term therapy. As to the ‘SAIB/additives/solvent’ system containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide-co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to months-long (16–60 d) smooth release of ROP could be achieved by varying the concentration (10–30%) and molecular weight (MW) of PLGA (10–50?kDa) or by employing a moderate MW of PEGylated ROP (～20 or ～30?kDa). With further increasing the conjugate MW to ～40?kDa, the contribution of drug elimination to its plasma retention seemed to surpass that of the SAIB-based system, resulting in that the system no longer had an obvious influence on the in vivo behavior of the conjugate. Besides, the results of host response confirmed that with less solvent being used, the SAIB-based systems showed a higher biocompatibility than the PLGA-based systems, suggesting that they could be freely chosen in the prevention and/or cure of chronic diseases.     

Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer

Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.     

唾液中氰离子的五氟苄基溴衍生气相色谱法测定

目的 建立用五氟苄基溴(PFB-Br)衍生气相色谱法,电子捕获检测器(ECD)定量测定唾液中氰离子(CN^-)的方法。方法 取微量唾液,加入缓冲溶液后用乙腈稀释定容,加入定量的PFB-Br摇匀,沸水浴30.0 min进行衍生反应,冷却后直接进样入气相色谱仪分离,以ECD检测器检测。结果 唾液中CN^-的质量浓度在0.25~200.0 mg/L呈线性关系,线性相关系数为0.999 4;以100.0 μl唾液量计算,方法最低检出浓度为0.07 mg/L,最低定量浓度为0.25 mg/L;方法的批间精密度为2.4%~5.3%(n=6),批内精密度为1.1%~3.8%(n=6),加标回收率为100.7%~102.1%。唾液常见的无机离子Cl^-、F^-和SCN^-对测定结果均无干扰。样品可在4 ℃保存至少15 d。结论 该方法适用于唾液中氰离子测定,对氰化物中毒的应急检测有应用价值。     

医学院女大学生自主神经系统功能状况及其影响因素分析

目的通过对医学院女大学生心率变异性的测量,了解其自主神经系统功能状况,分析其影响因素,为改善女大学生自主神经功能,促进其身心健康提供科学依据。方法 2015年6-10月选取422名吉林省某综合大学医学院女大学生为研究对象,采取自填式问卷方法,对其心率变异性进行测查。结果医学院女大学生自主神经系统活性偏低的检出率为37.0%,自主神经系统均衡性异常的检出率为71.1%;多因素Logistic回归结果显示,压力大和睡眠质量差分别是医学院女大学生自主神经系统活性和自主神经系统均衡性的独立影响因素(P<0.05)。结论医学院女大学生自主神经功能异常问题突出,应及时采取缓解压力、改善睡眠质量、加强体育锻炼等措施提高自主神经功能,促进女大学生身心健康。