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Three new glycosides (1–3), together with six known ones (4–9), were isolated from the root bark of Lycium chinense. Their structures were elucidated on the basis of MS and NMR spectroscopic data. Five compounds (3, 5, 6, 8, and 9) exhibited potent antihyperlipidemic activities in HepG2 cells as assessed by Oil Red O staining and significant inhibition of intracellular triglyceride (TG) levels, whereas two compounds (5 and 9) significantly reduced total cholesterol (TC) levels. [ABSTRACT FROM AUTHOR]

Silk was easily dyed in traditional textile industry because of its strong affinity to many colorants. Herein, the biocompatible silk fibroin was firstly extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano-platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily encapsulated into SFNPs with a very high encapsulation efficiency reaching to 97.7 ± 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle size of 209.4 ± 1.4 nm and a negative zeta potential of −31.9 mV, exhibiting a good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release profile of ICG in vitro, and only 24.51 ± 2.27% of the encapsulated ICG was released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal effect than free ICG after exposure to near-infrared irradiation. The temperature of ICG-SFNPs rapidly increased by 33.9 °C within 10 min and maintained for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in vitro, and a strong red fluorescence of ICG was observed in cytoplasm for cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through vein injection. Moreover, the temperature of tumor site was rapidly rising up to kill tumor cells after local NIR irradiation. After treatment, its growth was completely suppressed with the relative tumor volume of 0.55 ± 033 while free ICG of 33.72 ± 1.90. Overall, ICG-SFNPs may be an effective therapeutic means for intraoperative phototherapy and imaging. [ABSTRACT FROM AUTHOR]

Introduction:The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention. Areas covered:This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention. Expert Commentary:We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed. [ABSTRACT FROM PUBLISHER]

Ca-alginate-poly- l-lysine-alginate (APA-Ca) and Ba-alginate-poly- l-lysine-alginate (APA-Ba) microcapsules were prepared and their thickness and surface were examined by light microscopy and scanning electron microscopy. Specifically, light microscopy with frozen section was used to visualize and quantify the thickness of APA membrane, and monitor temporal changes in the thickness of microcapsules during a month long culture in vitro. The section graph of APA microcapsule represents the accurate measurement of layer thickness of APA-Ca with diameter 900 ± 100 and 500 ± 100 μm at 6.01 ± 1.02 and 9.54 ± 2.42 μm ( p < 0.05), and layer thickness of APA-Ba with diameter 900 ± 100 and 500 ± 100 μm at 5.47 ± 0.90 and 8.21 ± 1.97 μm ( p < 0.05), regardless of the alginate composition used to generate the microcapsules. The microcapsule was stable during the culture for 30 days in vitro. Field emission scanning electron microscopy with freeze drying method was used to detect the surface and thickness of dried microcapsules. From the results, the outer surface of APA-Ca and APA-Ba membrane were smooth and dense, the film thickness of the APA-Ca was about 450-690 nm, while the APA-Ba was approximately 335 nm. In vivo experiment, little significant difference was seen in the change of film thickness of microcapsules in intrapertioneal site for 30 days after transplantation ( p > 0.05), except that the recovery of APA-Ba was higher than the APA-Ca microcapsules. The paper showed an easy method to prepare APA-Ca and APA-Ba, and examine their thickness and surface, which could be utilized to study other types of microcapsules. [ABSTRACT FROM AUTHOR]

Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by1H,13C NMR, and mass spectral data. The test compounds were evaluated for theirin vitroanti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure–activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively. [ABSTRACT FROM AUTHOR]

Experiments in vitro and in vivo were designed to investigate tumor growth inhibition of chemotherapeutics-loaded liposomes enhanced by acoustic cavitation. Doxorubicin-loaded liposomes (DOX liposomes) were used in experiments to investigate acoustic cavitation mediated effects on cell viability and chemotherapeutic function. The influence of lingering sensitive period after acoustic cavitation on tumor inhibition was also investigated. Animal experiment was carried out to verify the practicability of this technique in vivo. From experiment results, blank phospholipid-based microbubbles (PBM) combined with ultrasound (US) at intensity below 0.3 W/cm2 could produce acoustic cavitation which maintained cell viability at high level. Compared with DOX solution, DOX liposomes combined with acoustic cavitation exerted effective tumor inhibition in vitro and in vivo. The lingering sensitive period after acoustic cavitation could also enhance the susceptibility of tumor to chemotherapeutic drugs. DOX liposomes could also exert certain tumor inhibition under preliminary acoustic cavitation. Acoustic cavitation could enhance the absorption efficiency of DOX liposomes, which could be used to reduce DOX adverse effect on normal organs in clinical chemotherapy. [ABSTRACT FROM AUTHOR]

Ultrasound (US)-mediated cavitation of microbubbles has evolved into a new tool for organ-specific gene and drug delivery. This paper was to investigate the feasibility of acidic fibroblast growth factor (aFGF) intravenous delivery to the ischemic myocardium of rats by ultrasonic microbubbles modified with heparin. Heparin modified microbubbles (HMB) were prepared by the freeze-dried method. Acute myocardial infarction (AMI) model was established and the cardio protective effect of the aFGF combing with HMB (aFGF-HMB) under US-mediated cavitation technique was investigated. aFGF-HMB combined with US-mediated cavitation technique was examined by ECG. Ejection fraction (EF), fractional shortening (FS) and left ventricular diastolic diameter (LVDd) were measured to monitor the improvement of global myocardial contractile function. Myocardial tissue was stained with hematoxylin and eosine (HE) to evaluate the elaborate general morphology of the ischemic myocardium. From morphologic observation and echocardiography in rat heart, aFGF-HMB had suitable size distribution, physical stability and good acoustic resonance function. From AMI rat experiments, aFGF-HMB under US-mediated cavitation technique exerted aFGF cardio protective effect in ischemic myocardium. From histological evaluation, US-mediated cavitation of aFGF-HMB showed improvement of myocardial ischemia. With the visual imaging and US-triggered drug release advantages, US-mediated cavitation of aFGF-HMB might be developed as a novel technique for targeting delivery of aFGF into ischemic myocardium. [ABSTRACT FROM AUTHOR]

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes-propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index == 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents. [ABSTRACT FROM AUTHOR]

An in vivo study on enhancing epirubicin hydrochloride (EPI) inhibition on tumor growth by ultrasound (US) was reported. Five-week-old male nude mice were used and HL-60 cells were s.c. (subcutaneous injection) inoculated in axilla of these mice. Six groups were designed and five consecutive treatments were applied to investigate the inhibition on tumor growth and body weight growth. US applied locally to the tumor resulted in a substantially increased drug uptake in tumor cells. The inhibition on tumor growth depended on the position of drug injection and phospholipid-based microbubble (PMB) application. Tumor growth rate under group 1 (PMB+US) was similar to that of blank control. The order of the inhibition on tumor volume growth was: group 4 (s.c. EPI+PMB+US) > group 5 intraperitoneal (i.p. EPI+PMB+US) > group 2 (i.p. EPI) > group 3 (s.c. EPI+US) > group 1 (PMB+US). Similar conclusion was obtained from experimental measurements of tumor weight change. The order of animal survival status for EPI administration groups was: group 4 > group 5 > group 2 > group 3. Chemotherapeutic drug inhibition on tumor growth could be enhanced by local US combined with PMB, which might provide a potential application for US-mediated chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. Aim: In this study, a new heparin–poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy (1H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP–poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. Results: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5°C, whereas that of the same concentration of poloxamer 188 was 37.3°C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Conclusion: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the factors for enhancing the susceptibility of cancer cells to chemotherapeutic drug by ultrasound microbubbles. Ultrasound (US) combined with phospholipid-based microbubbles (MB) was used to enhance the susceptibility of colon cancer cell line SWD-620 to anticancer drugs Topotecan hydrochloride (TOP). Experiments were designed to investigate the influence of main factors on cell viability and cell inhibition, such as US intensity, MB concentration, drug combination with MB, asynchronous action between US triggered cavitation and drug entering cell, MB particle size. US exposure for 10 sec with US probe power at 0.6 W/cm2 had satisfied cell viability. Treated with US combined with 15% MB, cell viability maintained more than 85% and cell inhibition 86.16%. Under optimal US combined with MB, TOP showed much higher cell inhibition than that of only TOP group. Cell inhibition under short delayed time (<2 h) for TOP addition did not show obvious difference. In terms of MB particle size, the order of cell inhibition was: Mixture > Micron bubble part > Nanometer bubble part. US combined with MB can enhance the susceptibility of cancer cells to chemotherapeutic drug, which may provide a potential method for US-mediated tumor chemotherapy. [ABSTRACT FROM AUTHOR]

This work was to compare the encapsulation efficiency and ultrasound-triggered release for protein between microbubbles and liposomes. Bovine serum albumin (BSA) was used as a model. Final ratios between BSA and HPC in microbubbles and liposomes were 1 : 5, 1 : 7 and 1 : 10, respectively. Morphologic characteristics and contrast enhancement of loaded microbubbles and liposomes were measured. Encapsulation efficiency and ultrasound-stimulated release profile were detected. The mean size of loaded microbubbles and liposomes was 3.4 µm and 1.7 µm, respectively. Encapsulation efficiency of microbubbles had an inverse relationship with the ratio between BSA and HPC, while loaded liposomes remained nearly unchanged in the designed range of the ratio between BSA and HPC. Microbubbles resulted in significant enhancement of CnTi images. After ultrasound, more than 90% of the entrapped BSA was released from microbubbles, but less than 5% of BSA released from liposomes. Microbubbles are a promising delivery system for proteins. [ABSTRACT FROM AUTHOR]

Both fibroblast growth factor 2 (FGF2) and luteinizing hormone (LH) have been reported to regulate androgen production in Leydig cells in progenitor Leydig cells. The objective of the present study is to examine the regulation of androgen production in rat immature Leydig cells (ILCs). ILCs were isolated from 35-day-old rat testes and cultured in DMEM/F12 medium with LH (1 ng/ml) or FGF2 (10 ng/ml). 5α-Androstane-3α, 17β-diol (3α-DIOL), the primary androgen in ILCs, and testosterone (T) were measured by Radioimmuno assay. The results showed the LH stimulated androgen production in ILCs, and FGF2 did not. However, FGF2 decreased the LH-stimulated androgen production. Real-time PCR and enzyme assay showed that FGF2 decreased levels of several steroidogenic enzymes, inhibited the expressions of steroidogenic acute regulatory (StAR) protein and steroidogenic factor 1 ( Nr5a1) in LH-stimulated ILCs. FGF2-mediated inhibition of Nr5a1gene expression may be the mechanism through which FGF2 inhibits LH-stimulated androgen production. [ABSTRACT FROM AUTHOR]

Background: Ultrasonic microbubbles are used as ultrasound-triggered delivery carriers for protein drugs. Aim: This work was to prepare stabilized protein-loaded phospholipid-based ultrasonic microbubbles (PUM) and to determine its value as a protein delivery system. Method: Bovine serum albumin (BSA) was used as a model protein drug. BSA-containing PUM were prepared by dissolving lyophilized PUM powder in BSA solution. The particle size and microbubble concentration of BSA-containing PUM were measured. The BSA encapsulation efficiency as a function of BSA concentration was determined. Contrast enhancement of BSA-containing PUM in vivo was detected. The release profile of BSA from PUM was also investigated. Results: The mean particle size and microbubble concentration of PUM were unchanged by the presence of BSA for at least 30 minutes after preparation. The net amount of BSA entrapped in PUM was maintained unchanged with increasing BSA concentration. BSA-containing PUM were shown easily to be visible in in vivo rabbit kidney. There was no difference in echogenicity between the loaded and unloaded PUM. Ultrasound duration had a positive relationship with BSA release. Ultrasound of 30 seconds stimulated 94.1% and 93.3% of BSA release from PUM solutions containing 0.3% and 1.5% BSA, respectively. Conclusions: Protein-loaded PUM exhibited satisfactory physical characteristics and were potent for using in ultrasound-triggered delivery. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the application of ultrasonic gas-filled liposomes in enhancing transfer for breast cancer-related antisense oligonucleotides in vitro. An antisense oligodeoxynucleotide (AS-ODN) sequence, HA2741, modified with luciferase reporter plasmid, was used in evaluating the enhancing effect of gas-filled liposomes for gene transfer in breast cancer cells. Some important factors on HA 2741 transfection efficiency, such as wave intensity, ultrasound duration, gas-filled liposome concentration, and HA2741 concentration, were tested, respectively. Transfection efficiency was detected by fluorescence microscopy. Cell viability was verified by propidium iodide assay. Reverse-transcriptase polymerase chain reaction and immunocytochemistry were used to detect the inhibitory effect of HA2741 on HER-2 expression. All the four factors (wave intensity, ultrasound duration, gas-filled liposome concentration, and HA2741 concentration) showed a positive effect on AS-ODN transfection efficiency. However, these factors had a negative effect on cell viability. Considering all the factors investigated, the maximum transfection efficiency with minimum cell viability achieved under 2% gas-filled liposome mixed with 80 nmol/L HA2741 for 30-second ultrasound exposure at -3.0dB wave intensity, which gave an overall transfection efficiency exceeding 90% and a cell viability near 90%. Under controlled conditions, ultrasound-mediated AS-ODN transfer, enhanced by gas-filled liposomes, may represent an effective, safe avenue for cancer-related gene delivery. [ABSTRACT FROM AUTHOR]

Curcumin is an excellent lead compound with a variety of bioactivity. Recent articles reported that curcumin's instability and low bioavailability in vivo are mainly due to its easily decomposable β-diketone moiety. With the aim of bioactive curcumin analogs with better pharmacokinetic property, we present here 11 bis(arylmethenyl)cyclopentanones similar to curcumin and without β-diketone moiety by reacting relevant arylaldehydes and cyclopentanones. The analogs were structurally determined by 1HNMR and MS spectra, and the crystal structure of 6 was analyzed by X-ray diffraction. Their antibacterial activities in vitro against seven Gram-positive and Gram-negative bacteria were tested, and their inhibition of TNF-α and IL-6 secretion in LPS-induced mouse macrophages was investigated using enzyme-linked immunosorbent assay. It was observed that several derivatives displayed higher activity when compared with curcumin, and most of the analogs exhibited activities against the ampicillin-resistant Gram-negative Enterobacter cloacae. [ABSTRACT FROM AUTHOR]

Zinc (Zn), copper (Cu) and iron (Fe) are essential minerals that are required for a variety of biomolecules to maintain the normal structure, function, and proliferation of cells. These metals can be toxic in excessive amounts, especially in certain genetic disorders. The homeostasis of these trace elements results from a tightly coordinated regulation by different proteins involved in their uptake, excretion and intracellular storage/trafficking. Through the Fenton reaction, Cu and Fe under a non protein-binding condition, can generate various reactive oxygen species, damaging tissues or cells. Abnormal metabolism of Zn, Cu and Fe can lead to several chronic pathogenesis, such as diabetes or diabetic complications. These pathogenic conditions appear to be prevalent in Zn and Cu deficiency, as well as Cu and Fe overload. In the Fe and Cu overloading conditions, Fe and Cu chelating drugs could be used to control diabetes and diabetic complications. The essentiality, toxicity and roles of these metals in the pathogenesis of diabetes and diabetic complications are discussed. [ABSTRACT FROM AUTHOR]