New ingol-type diterpenes from the latex of Euphorbia resinifera.

Two new ingol-type diterpenes, euphoresins A-B (1-2), have been isolated from the methanol extract of Euphorbium, the latex of Euphorbia resinifera Berg. Their structures were established on the basis of extensive analyses of their HR-ESI-MS, IR, UV, 1D, and 2D NMR spectra. The absolute configurations were confirmed by Mosher's method and circular dichroism (CD) analyses. The two compounds were tested for their cytotoxic activities against MCF-7, U937, and C6 cancer cell lines, but they both exhibited little cytotoxic effect.

[Triterpenoids from Uygur medicine latex of Euphorbia resinifera].

Ten triterpenes compounds were isolated from the methanol extraction of the latex of Euphorbia resinifera by means of various chromatographic methods such as silica gel, ODS and semi-preparative HPLC, Their structures were identified by spectroscopic methods and physicochemical properties. These isolated compounds were identified as 3ß-hydroxy-25,26,27-trinor eupha-8-ene-24-oate (1), iso-maticadienediol (2), 25,26,27-trinorTirucall-8-ene-3ß-ol-4-acid (3), dammarendiol Ⅱ (4), eupha-8,24-diene-3-ol-26-al (5), lnonotusane C (6), eupha-8,24-diene-3ß-ol-7,11-dione (7), inoterpene A (8), inoterpene B (9), and eupha-24-methylene-8-ene-3ß-ol-7,11-dione (10). Among them, compound 1 was a new natural product, compounds 2-4 were firstly isolated from the Euphorbiaceae and compounds 5 and 6 were isolated from the genus Euphorbia for the first time. The cytotoxicity of the compounds 1-10 against MCF-7, U937 and C6 cancer cell lines was evaluated, but none of the compounds was active.

Preparation and characterization of novel carbon dioxide adsorbents based on polyethylenimine-modified Halloysite nanotubes.

New nano-sized carbon dioxide (CO2) adsorbents based on Halloysite nanotubes impregnated with polyethylenimine (PEI) were designed and synthesized, which were excellent adsorbents for the capture of CO2 at room temperature and had relatively high CO2 adsorption capacity. The prepared adsorbents were characterized by various techniques such as Fourier transform infrared spectrometry, gel permeation chromatography, dynamic light scattering, thermogravimetry, thermogravimetry-Fourier transform-infrared spectrometry, scanning electron microscopy and transmission electron microscopy. The adsorption characteristics and capacity were studied at room temperature, the highest CO2 adsorption capacity of 156.6 mg/g-PEI was obtained and the optimal adsorption capacity can reach a maximum value of 54.8 mg/g-adsorbent. The experiment indicated that this kind of adsorbent has a high stability at 80°C and PEI-impregnated adsorbents showed good reversibility and stability during cyclic adsorption-regeneration tests.

Large-scale aqueous synthesis of fluorescent and biocompatible silicon nanoparticles and their use as highly photostable biological probes.

A large-scale synthetic strategy is developed for facile one-pot aqueous synthesis of silicon nanoparticles (SiNPs) yielding ∼0.1 g SiNPs of small sizes (∼2.2 nm) in 10 min. The as-prepared SiNPs feature strong fluorescence (photoluminescence quantum yield of 20-25%), favorable biocompatibility, and robust photo- and pH-stability. Moreover, the SiNPs are naturally water dispersible, requiring no additional post-treatment. Such SiNPs can serve as highly photostable bioprobes and are superbly suitable for long-term immunofluorescent cellular imaging.

Biomembrane-Derived Nanoparticles in Alzheimer's Disease Therapy: A Comprehensive Review of Synthetic Lipid Nanoparticles and Natural Cell-Derived Vesicles.

Current therapies for Alzheimer's disease used in the clinic predominantly focus on reducing symptoms with limited capability to control disease progression; thus, novel drugs are urgently needed. While nanoparticles (liposomes, high-density lipoprotein-based nanoparticles) constructed with synthetic biomembranes have shown great potential in AD therapy due to their excellent biocompatibility, multifunctionality and ability to penetrate the BBB, nanoparticles derived from natural biomembranes (extracellular vesicles, cell membrane-based nanoparticles) display inherent biocompatibility, stability, homing ability and ability to penetrate the BBB, which may present a safer and more effective treatment for AD. In this paper, we reviewed the synthetic and natural biomembrane-derived nanoparticles that are used in AD therapy. The challenges associated with the clinical translation of biomembrane-derived nanoparticles and future perspectives are also discussed.

The liposomal daunorubicin plus tamoxifen: improving the stability, uptake, and biodistribution of carriers.

The synergistic effects of tamoxifen on the sensitivity of MCF-7 cells to daunorubicin have been reported. Whether the effects of daunorubicin on MCF-7/adr cells can be improved by tamoxifen in liposomes and how tamoxifen changes daunorubicin's behavior in vivo remains unclear. The aim of this study was to investigate the effects of tamoxifen on the uptake and biodistribution of daunorubicin liposomes by breast-cancer-resistant MCF-7/adr cells in vitro and in vivo. The uptake of liposomes by MCF-7/adr cells in vitro studies was measured using flow cytometry and laser confocal microscopy. The biodistributions of carriers and free drugs were evaluated by DiR dye using in vivo imaging. Tamoxifen obviously enhanced the cellular uptake of liposomes by MCF-7/adr cells in time-dependent manners. According to the results from in vivo imaging analysis, the mean fluorescence intensity of DiR liposomes with tamoxifen in the tumor regions of MCF-7/adr tumor-bearing nude mice was much stronger than that of DiR liposomes alone (16,450 ± 1,331 versus 3,666 ± 321; n = 3). Pegylated liposomes elongated the existence of daunorubicin in the circulatory system and the enhanced permeability and retention effect enhanced its concentration in local tumor tissues, which may provide the precondition for tamoxifen further promoting the uptake by MCF-7/Adr cells in vivo. Using daunorubicin liposomes and tamoxifen together generates better biodistribution profiles in tumor tissue than using daunorubicin liposomes only, which contributes to improving the therapeutic effect of breast cancer treatment.

Application of neural stem cells in tissue-engineered artificial nerve.

OBJECTIVE: To observe the curative effect of neural stem cells (NSCs), which are used in tissue-engineered artificial nerve, on repairing rabbit 10-mm facial nerve defects. METHODS: Thirty-six Oryctolagus cuniculi were randomly divided into three groups (each group with 12 Oryctolagus cuniculi). In group A, chitosan conduit, collagen protein sponge, nerve growth factor (NGF), and NSCs were used. In group B, chitosan conduit, collagen sponge, and NGF were used. In group C, nerve autograft was performed. Electrophysiologic detection, histologic observation, and BrdU and S100 immunohistochemical examination were performed 12 weeks after operation. RESULTS: All observation items in group A were better than those in group B (P < 0.01), and there were no significant differences between group A and group C (P > 0.05). CONCLUSION: NSCs may be served as seed cells of peripheral nerve tissue engineering and be used in artificial nerve to repair facial nerve defects.

Multifunctional Zn doped hollow mesoporous silica/polycaprolactone electrospun membranes with enhanced hair follicle regeneration and antibacterial activity for wound healing.

Due to the complexity of the skin tissue structure, the regeneration of the entire skin, including skin appendages such as hair follicles, is a big challenge. In addition, skin trauma is often accompanied by bacterial infections that delay the wound healing. Therefore, developing wound dressings, which promote hair follicle regeneration and inhibit bacterial infection in the wound healing process, is of great clinical significance. In this study, Zn doped hollow mesoporous silica nanospheres (HMZS) were synthesized by a sol-gel method and a novel wound healing dressing was prepared by incorporation of drug ciprofloxacin hydrochloride (CiH)-loaded Zn containing mesoporous silica nanospheres (CiH-HMZS) into polycaprolactone (PCL) electrospun fibers. The CiH-HMZS/P nano-composite electrospun fibers exhibit the ability to promote angiogenesis and skin regeneration by releasing Si ions, and the activity to enhance hair follicle regeneration and inhibit bacterial growth by releasing zinc ions and achieve the synergistic antibacterial effect with both Zn ions and CiH in low concentrations. Thus, the CiH-HMZS/P nano-composite membrane is a promising multi-functional wound healing material for inhibiting bacterial growth in infected wounds and enhancing skin wound healing including hair follicle regeneration.

Nifedipine regulated periodontal ligament remodeling: an experimental study in rats.

OBJECTIVE: The aim of this study was to investigate the effects of nifedipine on periodontal ligament remodeling during orthodontic tooth movement. MATERIAL AND METHODS: Sixty male Sprague-Dawley rats were randomly divided into an orthodontic group and groups that received either 10 mg/kg or 40 mg/kg nifedipine (NIF). Immunohistochemical staining and image analysis were used to investigate the expression of matrix metalloproteinase (MMP)-1, -10, -13 and collagen-I in PDL, and maxillary 1st molar displacement was measured. RESULTS: Expression of MMP-1, -10, and -13 was significantly decreased in both NIF groups, while collagen-I expression was markedly increased. NIF significantly inhibited tooth movement. CONCLUSIONS: NIF affects the expression of MMP-1, -10, -13 and collagen-I and tooth movement induced by orthodontic force in rats, thus indicating that calcium channels might be important in mediating PDL remodeling.

Culture of osteoblasts on bio-derived bones.

OBJECTIVE: To study the effect of bio-derived bones, as substitutes of autogenous bone grafts and demineralized cadaver bones, on the attachment, spreading and proliferation of isolated osteoblasts. METHODS: Osteoblasts were isolated from the calvaria of a fetal rabbit through sequential collagenase digestion. In the attachment study, the osteoblasts labeled with 3H-leucine were incubated with the bio-derived bone materials in sterile microcentrifugable tubes for 15, 90 and 180 minutes, and 24 hours, respectively. The attached cells were collected and the radioactivity was measured with liquid scintillation spectrometry. In the proliferation study, the osteoblasts were cultured with the bio-derived bone materials for 24 hours and 3H-thymidine was added during the last 2 hours of the incubation. The attached cells were collected and the radioactivity was measured with liquid scintillation spectrometry. Osteoblasts were seeded on the bone graft materials for 60 or 120 minutes, 24 or 48 hours, and 3 or 7 days, then the co-culture was processed for scanning electron microscopy to observe the interaction of osteoblasts and the bio-derived bone materials. RESULTS: Osteoblasts attached to the bio-derived bone materials in a time-dependent manner. There were significantly (P<0.05) more attached cells after 180 minutes than after 15 and 90 minutes of incubations (P<0.05). Osteoblasts were proliferated in a large amount on the surface and in the materials. Osteoblasts seeded onto 100 mg bio-derived bones resulted in significantly (P<0.05) more measurable proliferation than those seeded onto 10 mg bones. Osteoblasts appeared round as they attached to the materials, then flattened and spread over with time passing. CONCLUSIONS: Bio-derived bones can provide a good environment for the attachment and proliferation of osteoblasts.

Novel esophageal squamous cell carcinoma bone metastatic clone isolated by scintigraphy, X ray and micro PET/CT.

AIM: To establish a Chinese esophageal squamous cell carcinoma (ESCC) cell line with high bone metastasis potency using (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) micro-pinhole scintigraphy, X ray and micro-positron emission tomography/computed tomography (PET/CT) for exploring the mechanism of occurrence and development in esophageal cancer. METHODS: The cells came from a BALB/c nu/nu immunodeficient mouse, and oncogenic tumor tissue was from a surgical specimen from a 61-year-old male patient with ESCC. The cell growth curve was mapped and analysis of chromosome karyotype was performed. Approximately 1 × 106 oncogenic cells were injected into the left cardiac ventricle of immunodeficient mice. The bone metastatic lesions of tumor-bearing mice were detected by (99m)Tc-MDP scintigraphy, micro-PET/CT and X-ray, and were resected from the mice under deep anesthesia. The bone metastatic cells in the lesions were used for culture and for repeated intracardiac inoculation. This in vivo/in vitro experimental metastasis study was repeated for four cycles. All of the suspicious bone sites were confirmed by pathology. Real-time polymerase chain reaction was used to compare the gene expression in the parental cells and in the bone metastatic clone. RESULTS: The surgical specimen was implanted subcutaneously in immunodeficient mice and the tumorigenesis rate was 100%. First-passage oncogenic cells were named CEK-Sq-1. The chromosome karyotype analysis of the cell line was hypotriploid. The bone metastasis rate went from 20% with the first-passage oncogenic cells via intracardiac inoculation to 90% after four cycles. The established bone metastasis clone named CEK-Sq-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic and lumbar vertebrae, scapula and femur. The bone metastasis lesions were successfully detected by micro-pinhole bone scintigraphy, micro-PET/CT, and X-ray. The sensitivity, specificity and accuracy of the micro-pinhole scintigraphy, X-ray, and micro-PET/CT imaging examinations were: 89.66%/32%/80%, 88.2%/100%/89.2%, and 88.75%/77.5%/87.5%, respectively. Some gene expression difference was found between parental and bone metastasis cells. CONCLUSION: This newly established Chinese ESCC cell line and animal model may provide a useful tool for the study of the pathogenesis and development of esophageal carcinoma.

[Preparation and ectopic osteoinduction study of macroporous bone substitute with calcium phosphate cements and rhBMP-2 loaded gelatin microspheres].

OBJECTIVE: To prepare macroporous bone substitute composed of calcium phosphate cements and rhBMP-2 loaded gelatin microspheres, and to investigate ectopic osteoinduction of the composite. METHODS: After being prepared by improved emulsified cold-condensation method and crosslinked by 5% genipin solution,gelatin microspheres (GMs) were observed by scanning electron microscope (SEM) and loaded with rhBMP-2 by adsorption. Macroporous bone substitute was developed by mixing calcium phosphate cement (CPC) with 2.5% GMs, being as the experimental group,and CPC with rhBMP-2 was the control group. After the both composites had been soaked in the sodium chloride for 1 week or 3 weeks, compressive strength of the composites were tested, and the cross-sections were observed by SEM. Concentrations of rhBMP-2 in the solutions at different time by ELISA method and the cumulative drug release amount was calculated. The composites had been implanted in the muscle bags of the mouses for 3 weeks. Then the tissues around the materials were collected, stained by hematoxylin and eosin, and Ca and ALP in the tissues were also measured. RESULTS: Gelatin microspheres were spherical with diameters of (62 +/- 18) microm. Macropores appeared in the experimental materials 1 week and 3 weeks after being soaked,and total porosity, macroporosity, cumulative release amount of rhBMP-2 in the experimental group were higher than that in the control. But compressive strength of the experimental group was lower than that of the control group 3 weeks after being soaked. Results of HE stain showed chondral formation in both groups, but there were more chondral tissues in the experiment group, and so were the concentrations of Ca and ALP. CONCLUSION: Macroporous calcium phosphate cement can be prepared by using rhBMP-2 loaded gelatin microspheres, and it is an excellent bone substitute due to it's proterty of promoting rhBMP release and powerful ectopic osteoinduction.

New cobalt-mediated radical polymerization (CMRP) of methyl methacrylate initiated by two single-component dinuclear ß-diketone cobalt (II) catalysts.

Two dinuclear cobalt complexes based on bis-diketonate ligands (ligand 1: 3,3'-(1,3-phenylene)bis(1-phenylpropane-1,3-dione); ligand 2: 3,3'-(1,4-phenylene)bis(1-phenylpropane-1,3-dione)) were successfully synthesized. The two neutral catalysts all showed satisfactory activities in the cobalt-mediated radical polymerization (CMRP) of methyl methacrylate (MMA) with the common initiator of azodiisobutyronitrile (AIBN). The resulting polymerizations have all of the characteristics of a living polymerization and displayed linear semilogarithmic kinetic plots, a linear correlation between the number-average molecular weight and the monomer conversion, and low polydispersities. Mono- or dicomponent low polydispersity polymers could be obtained by using the two dinuclear catalysts under proper reaction conditions. All these improvements facilitate the implementation of the acrylate CMRP and open the door to the scale-up of the syntheses and applications of the multicomponent low polydispersity polymers.

Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid).

The development of biodegradable materials with controllable degradation properties is beneficial for a variety of applications. Poly(glycerol-sebacate) (PGS) is a promising candidate of biomaterials; so we synthesize a series of poly(glycerol, sebacate, glycolic acid) (PGSG) with 1:2:0, 1:2:0.2, 1:2:0.4, 1:2:0.6, 1:2:1 mole ratio of glycerol, sebacate, and glycolic acid to elucidate the relation of doped glycolic acid to the degradation rate and mechanical properties. The microstructures of the polymers with different doping of glycolic acid were dissimilar. PGSG with glycolic acid in the ratio of 0.2 displayed an integral degree of ordering, different to those with glycolic acid in the ratio of 0, 0.4, 0.6, and 1, which showed mild phase separation structure. The number, DeltaH(m), and temperature of the PGSG melting peaks tended to decrease with the increasing ratio of doped glycolic acid. In vitro and in vivo degradation tests showed that the degradation rate of PGSG with glycolic acid in the ratio of 0.2 was slowest, but in the ratio range of 0, 0.4, and 0.6, the degradation rate increased with the increase of glycolic acid. All PGSG samples displayed good tissue response and anticoagulant effects. Our data suggest that doping glycolic acid can modulate the microstructure and degree of crosslinking of PGS, thereby control the degradation rate of PGS.

The application of poly (glycerol-sebacate) as biodegradable drug carrier.

Poly (glycerol-sebacate) (PGS) is an elastomeric biodegradable polymer which possesses the ideal properties of drug carriers. In the present study, we prepared a series of PGS implants (5-FU-PGSs) loaded with different weight percent of 5-fluorouracil (2, 5, 7.5 and 10%). We studied the infrared spectrum properties, in vitro degradation and drug release, in vivo degradation and tissue biocompatibility of 5-FU-PGSs, in order to provide detailed information for the application of PGS as biodegradable drug carrier in cancer therapy. Macroscopically, all 5-FU-PGS wafers in phosphate buffer solution (PBS) kept their geometries during the degradation period of 30 days. The in vitro degradation rates of 5-FU-PGSs were accelerated when higher concentration of 5-FU was doped. Scanning electron microscopy observation showed that the surfaces of 5-FU-PGSs with higher concentration of 5-FU had irregular pits. The cumulative drug release profiles of 5-FU-PGSs exhibited a biphasic release with an initial burst release in the first day. After 7 days, almost 100% cumulative release of 5-FU was found for all 5-FU-PGSs.The degradation rate of 5-FU-PGSs in vivo was much quicker than that in vitro. Hematoxylin and eosin staining showed that no remarkable inflammations were observed in the tissue surrounding 5-FU-PGS implants, suggesting 5-FU-PGSs had good biocompatibility and no tissue toxicity. In vitro anti-tumor activity assay suggested that 5-FU-PGSs exhibited anti-tumor activity through sustained-release drug mode. These results demonstrate that PGS is a candidate of biodegradable drug carriers.