As an important ABC transporter, breast cancer re-sistance protein ( BCRP) plays an important role in tumor multi-drug resistance. Many laboratories are focusing on BCRP to re-verse multidrug resistance. We summarize in the paper the re-search progress on the regulation of BCRP expression, subcellu-lar localization, ATP-dependence, inhibition or modulation of its transport activity and potential clinical treatment strategies in or-der to provide theoretical support and some new research ideas for the reverse of multidrug resistance in clinic.

Bone metastasis is a common complication in patients with malignant carcinoma. This process involves interactions between metastatic cancer cells and bone microenvironment. The two common pathological types are osteolytic and osteoblastic metastasis. Damage to the bone is closely associated with tumor growth.

Insulin-like growth factor-Ⅰ can promote the breast cancer formation, development and metastasis. According to the characteristic of insulin-like growth factor pathway, the inhibition of insulin-like growth factor pathway signaling can inhibit the growth and metastasis of breast cancer, which is of great significance for breast cancer prevention and treatment.

BACKGROUND:As a new kind of adult stem cells, adipose-derived stem cells get more and more attention, because of rich source, drawing materials easily and powerful proliferation. OBJECTIVE:To isolate and culture adipose-derived stem cells from the epididymal adipose tissue in mice, and to identify their biological characteristics. METHODS:Adipose tissue was obtained from epididymis in mice by aseptical y cutting. The tissue was digested using col agenase. Adipose-derived stem cells were separated and purified by using one digestion, multiple col ection method and differential adhesion method. The morphology of adipose-derived stem cells was observed using inverted microscopy and transmission electron microscopy. Growth curve of adipose-derived stem cells was drawn. Immunophenotype of adipose-derived stem cells was identified by flow cytometry. Adipose-derived stem cells were induced to differentiate into adipocytes and osteocytes using cellinductors. Compatibility of adipose-derived stem cells and col agen scaffold material was observed using scanning electron microscope. RESULTS AND CONCLUSION:Adipose-derived stem cells exhibited long spindle-like or fibroblast-like appearance, grew intensively and arranged in scrol and fascicular shape. In vitro, adipose-derived stem cells could be passaged to passage 9 under the inverted microscope. Under the transmission electron microscope, adipose-derived stem cells showed abundant microvil i on the cellsurface. The nuclei were big in size. Some organel es were seen in cytoplasma, such as mitochondria and rough endoplasmic reticulum. Adipose-derived stem cells expressed CD44 and CD29, did not express CD34. After inducing by inductor, many smal lipid droplets were seen in the cytoplasm of adipose-derived stem cells. The smal lipid droplets were dyed red with oil red O. After induction of osteogenic inductor, the boundary line among adipose-derived stem cells was not clear and the structure of cells was fuzzy in the growth-intensive areas. There were many strong refractive granular material deposits at that field after dyeing with alizarin red. Scanning electron microscope revealed that adipose-derived stem cells were spread on the col agen scaffold. Results suggested that adipose-derived stem cells isolated by this method could amplify in vitro and stably subcultured. Under a certain inducing condition, adipose-derived stem cells could differentiate into osteoblasts and adipocytes, which showed a good compatibility with col agen scaffold.

OBJECTIVE:To prepare Hyaluronic acid-methyl collagen-terpolymer (HEMA-MMA-MAA)/Doxorubicin com-pound membranes-loaded tantalum stent,and to optimize the formulation. METHODS:Electrostatic self-assembly reaction was ad-opted to prepare compound membranes using metal tantalum stent as carrier,hyaluronic acid,methyl collagen and terpolymer as ex-cipients. With 1 and 30 d accumulative release rate as index,orthogonal test was used to optimize mass concentrations of hyaluron-ic acid,methyl collagen and terpolymer,and validated. The drug release behavior in vitro were investigated. RESULTS:The opti-mal formulation was as hyaluronic acid 1 mg/ml,methyl collagen 4.5 mg/ml and terpolymer 100 mg/ml. 1 and 30 d accumulative release rates of prepared tantalum stent were 7.57%(RSD=2.3%,n=3) and 84.14%(RSD=2.1%,n=3),respectively. 20 d later,dissolution rate approximated to zero level rate of drug release. CONCLUSIONS:Hyaluronic acid-methyl collagen-terpoly-mer/Doxorubicin compound membranes-loaded tantalum stent with sustained-release property is prepared successfully.

Objective To observe the effects of PM2.5 exposure on A549 cells,and explore the mechanism of toxicity. Method The concentra?tions of PM2.5 exposure were determined utilizing cell viability assay. The morphological characteristics of exposed cell were observed with trans?mission electron microscope. Using big date from RNA?Seq and qRT?PCR,the mechanism was explored. Results The final concentration of PM2.5 exposure was 50μg/cm2;morphological detection showed that chromatin condensation after exposure which was also found on the boundary of nuclear membrane. KEGG pathway analysis and interaction network were finished ,and 8 kinds of apoptosis?related genes were found to be in?volved in the process of damage. Conclusion PM2.5 induces apoptosis in A549 cells by stimulating the changes of apoptosis?related genes ex?pressions.

We applied Lempel-Ziv complexity (LZC) combined with brain electrical activity mapping (BEAM) to study the change of alertness under sleep deprivation in our research. Ten subjects were involved in 36 hours sleep deprivation (SD), during which spontaneous electroencephalogram (EEG) experiments and auditory evoked EEG experiments-Oddball were recorded once every 6 hours. Spontaneous and evoked EEG data were calculated and BEAMs were structured. Results showed that during the 36 hours of SD, alertness could be divided into three stages, i. e. the first 12 hours as the high stage, the middle 12 hours as the rapid decline stage and the last 12 hours as the low stage. During the period SD, LZC of Spontaneous EEG decreased over the whole brain to some extent, but remained consistent with the subjective scales. By BEAMs of event related potential, LZC on frontal cortex decreased, but kept consistent with the behavioral responses. Therefore, LZC can be effective to reflect the change of brain alertness. At the same time LZC could be used as a practical index to monitor real-time alertness because of its simple computation and fast calculation.
Attention ; physiology ; Brain Mapping ; Electroencephalography ; Evoked Potentials ; Humans ; Nonlinear Dynamics ; Sleep Deprivation

Objective To explore the role of tumor inhibition of enhancer binding protein C/EBPα in the leukemic mice. Methods BALB/c nude mice were randomly divided into three groups. Three kinds of cells including pEGFP-C/EBPα-K562 cells, pEGFP-K562 cells and K562 cells as the control were injected into mice separately through the subcutaneous and tail vein, and subcutaneous tumors and leukemic models were formed. The changes of tumors were observed and the apoptosis of cells was detected by TUNEL; The capacity of proliferation of leukemia cells was observed in the bone marrow and the peripheral blood by Wright-Giemsa staining. The expression of genes of related to proliferation was detected by RT-PCR. Results The quality and the max diameter of tumors in the pEGFP-C/EBPα-K562 group were smaller than that of pEGFP-K562 group and K562 control group [(2.4±0.1) g vs (5.1±0.3) g and (5.7±0.4) g, both P ＜0.05; (11+2)mm vs (19+3) mm and (23+3) mm, both P ＜0.05]. More apoptosis cells were found in the pEGFP-C/EBPα-K562 group leukemic cells were found in the peripheral blood of leukemic models, and the proliferation of leukemic cells in the pEGFP-C/EBPo-K562 group were lower than that of other groups, accompany by the conspicuous cell differentiation. p53 was significantly elevated by RT-PCR, while down-regulated of c-myc.Conclusion Enhancer binding protein C/EBPα promote the apoptosis of cells and inhibit the proliferation of leukemia cells in leukemia mice, and further induce the cell differentiation. The inhibition of enhancer binding protein C/EBPα in the leukemia may have effect through the regulation of related genes.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.