MiRNAs can function as oncogenes or tumor suppressor genes. The abnormal expression of miRNAs leads to tumor malignant phenotypes, such as cell proliferation, apoptosis, invasion and metastasis, through which it is involved in the process of tumor initiation, progression and transcriptional regulation network. Therefore, it is important to clarify the mechanism of miRNA involved in the process of tumor initiation and progression. MiRNA regulation mechanism in tumor initiation and progression includes one-to-many and many-to-one regulation between TF-to-miRNA and miRNA-to-target gene, which increases the complexity of miRNA regulation, thus affecting the biological behavior of the tumor, The expression and activity of Drosha and Dicer in the process of miRNA affect the synthesis of mature miRNA and involve in the process of tumor initiation and progression;ceRNA may bind with miRNA by competing with miRNA targeting genes and affect biological function of miRNA as miRNA inhibitor. Therefore the abnormal expression and structure of ceRNA is an important molecular mechanism of tumor initiation and progression. This complicated regulation network comprised by multi-dimensional regulation model and specific regulation of tumor initiation and progression provides impetus to exploring the functional restoration of miRNA as a novel target for cancer diagnosis and therapy.

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose

Objective To compare the dosimetry difference among three-dimensional conformal radiotherapy (3 DCRT),simplified intensity-modulated radiotherapy (sIMRT) and intensity-modulated radiotherapy (IMRT) in whole pelvic irradiation in postoperative rectal carcinoma,in order to optimize the protocol for clinical practice.Methods From 2006 to 2008,10 patients with stage II and ID rectal cancer after radical resection (Dixon surgery) participated in this study.3DCRT,sIMRT and IMRT were performed for each patient.The dose distribution of target volume and normal tissues,conformal index (CI) and HI were analyzed using the dose-volume histogram (DVH).Results The CI for PTV of IMRT and sIMRT was superior to that of 3DCRT.3DCRT had the best HI in PTV target area dose distribution,while IMRT was similar with sIMRT,however,there were no significant difference among them.As regarded as the protection on organs at risk,for bladder,IMRT was superior to 3DCRT and slightly better than sIMRT;for small intestine,sIMRT showed better performance than 3DCRT while IMRT was better than sIMRT but with no significant difference;for colon,no dosimetry difference was found among three plans;for caput femoris,IMRT and sIMRT were better than 3DCRT.Additionally,sIMRT was similar to 3DCRT in MU of segments,but significantly lower than IMRT.The mean values of total MU for 3DCRT,sIMRT and IMRT were 569.73 ±48.69,542.97 ±69.78,and 770.25 ±73.12,respectively.Conclusions All of 3DCRT,sIMRT and IMRT could provide target area with sufficient and accurate dose,meanwhile they could also protect organs at risk well on rectal cancer after radical resection.Compared with 3DCRT plan and IMRT plan,sIMRT plan might be the optimal plan for clinical practice.

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.

OBJECTIVE: To localize and define the region of nucleus export signal (NES) on BRD7, and determine the role of this region in nucleus export of the external protein. METHODS: Based on an in vitro expressed model of green fluorescence protein (GFP), we performed DNA walking analysis to set BRD7 into several sections according to the structural characteristics of BRD7, investigated the effect of different sections of BRD7 on nucleus export of GFP, defined the region of nucleus export signal sequence of BRD7, and further ascertained the content of amino acids in BRD7 and potential localization of BRD7 NES by bioinformatics. RESULTS: B7C1 fragments ranged from aa219 to aa450 in BRD7 were found to target the external protein GFP into the cytoplasm detected by GFP direct fluorescence, which could be inhibited by NES inhibitor Leptomycin B (LMB). This region was rich in hydrophobic amino acid residues but no typical NES with characteristics of leucine-rich sequence by bioinformatics. CONCLUSION The region from aa219 to aa450 is primarily defined as an atypical NES in BRD7.
Animals ; Base Sequence ; COS Cells ; Cell Nucleus ; metabolism ; Chlorocebus aethiops ; Chromosomal Proteins, Non-Histone ; genetics ; metabolism ; Cytoplasm ; metabolism ; Escherichia coli ; genetics ; metabolism ; Green Fluorescent Proteins ; genetics ; Humans ; Molecular Sequence Data ; Nuclear Export Signals ; Recombinant Proteins ; genetics ; metabolism

PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Cell Line ; Disease-Free Survival* ; Drug Therapy ; Humans ; In Vitro Techniques ; Methods ; Neoadjuvant Therapy ; Paclitaxel ; Porifera ; Prognosis ; Retrospective Studies ; RNA, Long Noncoding

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.