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.     

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。     

Acute phase protein, α – 1- acid glycoprotein (AGP-1), has differential effects on TLR-2 and TLR-4 mediated responses

Alpha-1-acid glycoprotein (AGP-1) is a major positive acute phase glycoprotein with unknown functions that likely play a role in inflammation. We tested its involvement in a variety of inflammatory responses using human AGP-1 purified to apparent homogeneity and confirmed its identity by immunoblotting and mass spectrometry. AGP-1 alone upregulated MAPK signaling in murine peritoneal macrophages. However, when given in combination with TLR ligands, AGP-1 selectively augmented MAPK activation induced by ligands of TLR-2 (Braun lipoprotein) but not TLR-4 (lipopolysaccharide). In vivo treatment of AGP-1 in a murine model of sepsis with or without TLR-2 or TLR-4 ligands, selectively potentiated TLR-2-mediated mortality, but was without significant effect on TLR-4-mediated mortality. Furthermore, in vitro, AGP-1 selectively potentiated TLR-2 mediated adhesion of human primary immune cell, neutrophils. Hence, our studies highlight a new role for the acute phase protein AGP-1 in sepsis via its interaction with TLR-2 signaling mechanisms to selectively promote responsiveness to one of the two major gram-negative endotoxins, contributing to the complicated pathobiology of sepsis.     

Expression of two drug-metabolizing cytochrome P450-enzymes in human salivary glands

Objective:  The oral cavity is constantly lubricated by saliva and even small amounts of xenobiotics and / or their metabolites in the saliva may affect the oral mucosa. Our aim was therefore to clarify if xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 are expressed in salivary glands.
Methods:  Formalin-fixed paraffin-embedded specimens from parotid (10), submandibular (7) and labial (10) salivary glands were examined immunohistochemically and by in situ hybridization for expression of CYP1A2 and CYP3A4 protein and mRNA.
Results:  CYP1A2 and CYP3A4 protein and mRNA were detected in ductal and seromucous / serous acinar cells in all gland types although to a varying degree and intensity. Mucous acinar cells were positive to a lesser extent.
Conclusion:  The results indicate a xenobiotic metabolizing capability of salivary glands. This may have implications for development of oral mucosal disease as a result of mucosal exposure to metabolites originating from internal sources (blood) as well as from saliva.     

CSF-1, RANKL and OPG regulate osteoclastogenesis during murine tooth eruption

During tooth eruption, osteoclast-mediated bone resorption predominates in alveolar bone along the occlusal surface rather than in bone basal to the tooth. CSF-1, RANKL and OPG, regulatory molecules essential for osteoclastogenesis, are expressed during eruption. However, it is unclear if these cytokines exhibit an expression pattern that correlates with sites of osteoclastogenesis in vivo. To address this issue, mouse mandibles, isolated from 1 to 14 days postnatal, were analysed for osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining as well as colony-stimulating factor-1 (CSF-1), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) mRNA expression using in situ hybridisation. Results showed that CSF-1, RANKL and OPG are expressed in a distinct temporal and spatial manner. In the occlusal region, osteoclast activity was maximal at day 5 and correlated with a relative high expression of CSF-1 and RANKL compared to OPG. In basal bone at this time point, osteoclast activity decreased despite persistent CSF-1 expression and was associated with increased expression of OPG compared to RANKL. By day 8, osteoclastogenesis declined and correlated with upregulation of OPG at the occlusal and basal regions, with this effect continuing throughout eruption. These findings suggest that the spatiotemporal pattern and relative abundance of CSF-1, RANKL and OPG during eruption are key determinants of site-specific osteoclast activity in bone surrounding the tooth. Targeting these cytokines to specific regions in alveolar bone may provide a mechanism for regulating osteoclastogenesis in dental disorders associated with altered tooth eruption.     

牙本质牙髓复合体的形成研究(二)牙本质牙髓复合体的在体形成研究

牙本质牙髓复合体在体形成研究包括牙齿发育完成后在各种因素下形成的第三期牙本质和成牙组织、细胞在口腔以外部位形成牙齿样结构两方面。一些细胞外基质分子和生长因子形成的网络调控在其形成中发挥关键性作用。对这些分子机理的研究将为临床牙髓病的生物保髓治疗和牙髓、牙齿再生替代治疗奠定了基础。