Treatment of rheumatoid arthritis with curcumin analog 3,5-bis(arylidene)-4-piperidone.

Rheumatoid arthritis (RA) is an inflammatory disease. Curcumin can inhibit NF-κB and reduce the expression of inflammation-related genes. Aim: To evaluate the potential development of 6d in the clinical treatment of inflammatory diseases such as RA. Methods: Using a skeleton fusion strategy to synthesize curcumin analogues for 6d. This work evaluates anti-inflammatory activity by conducting anti-arthritis experiments (adjuvant-induced RA models) on rats. Western blot and ELISA were used to detect the expression of inflammatory-related proteins and cytokines. Molecular docking analysis confirmed the binding effect of 6d with active sites. Conclusion: 6d inhibits NF-κB has a protective effect on arthritis caused by RA.

Maize, wheat, and soybean root traits depend upon soil phosphorus fertility and mycorrhizal status.

Strong effects of plant identity, soil nutrient availability or mycorrhizal fungi on root traits have been well documented, but their interactive influences on root traits are still poorly understood. Here, three crop species (maize, wheat and soybean) were grown under four phosphorus (P) addition levels (0, 20, 40 and 60 mg P kg-1 dry soil), and plants were inoculated with or without five combined arbuscular mycorrhizal fungal (AMF) species. Plant biomass, nutrient contents, root traits (including total root length, average root diameter, specific root length and root tissue density) and plants' mycorrhizal responses were measured. Crop species, P level, AMF, and their interactions strongly affected plant biomass and root traits. P fertilization promoted plant growth but reduced mycorrhizal benefits on plant biomass and nutrient uptake. Root traits of maize were sensitive to P addition only under the non-mycorrhizal condition, whilst most root traits of soybean and wheat plants were responsive to mycorrhizal inoculation but not P addition. Mycorrhizal colonization reduced the root plasticity in response to P fertility for maize but not for wheat or soybean. This study highlights the importance of soil nutrient fertility and mycorrhizal symbiosis in influencing root traits.

Enhanced efficiency and mechanism of low-temperature biochar on simultaneous removal of nitrogen and phosphorus by combined heterotrophic nitrification-aerobic denitrification bacteria.

In this study, three strains of heterotrophic nitrification-aerobic denitrification (HN-AD) capable of simultaneously removing phosphorus were isolated from activated sludge, and low-temperature coconut shell biochar was prepared. The metabolic effects of combined HN-AD bacteria on the total nitrogen (TN) and total phosphorus (TP) were investigated, and the enhanced efficiency and mechanism of low-temperature biochar on the combined bacteria were also explored. The results indicated that the combined bacteria could adapt to environmental impacts and multiple nitrogen sources. The low-temperature biochar containing more aliphatic carbon and oxygen-containing functional groups enhanced the metabolic activity of combined HN-AD bacteria and accelerated the electron transfer process during nitrogen and phosphorus degradation. The removal efficiencies of TN and TP increased by 68% and 88%, respectively, in the treatment of actual sewage by biochar attached with combined bacteria. The findings form a basis for the engineering utilization of HN-AD and are of great practical significance.

Artificial Assembled Macrophage Co-Deliver Black Phosphorus Quantum Dot and CDK4/6 Inhibitor for Colorectal Cancer Triple-Therapy.

In recent years, therapeutic strategies based on macrophages have been inspiringly developed, but due to the high intricacy and immunosuppression of the tumor microenvironment, the widespread use of these strategies still faces significant challenges. Herein, an artificial assembled macrophage concept (AB@LM) was presented to imitate the main antitumor abilities of macrophages of tumor targeting, promoting the antitumor immunity, and direct tumor-killing effects. The artificial assembled macrophage (AB@LM) was prepared through an extrusion method, which is to fuse the macrophage membrane with abemaciclib and black phosphorus quantum dot (BPQD)-loaded liposomes. AB@LM showed good stability and tumor targeting ability with the help of macrophage membrane. Furthermore, AB@LM reversed the immunosuppressive tumor microenvironment by inhibiting regulatory T cells (Tregs) and stimulating the maturation of antigen-presenting cells to activate the antitumor immune response through triggering an immunogenic cell death effect. More importantly, in the colorectal tumor model in vivo, a strong cooperative therapeutic effect of photo/chemo/immunotherapy was observed with high tumor inhibition rate (95.3 ± 2.05%). In conclusion, AB@LM exhibits excellent antitumor efficacy by intelligently mimicking the abilities of macrophages. A promising therapeutic strategy for tumor treatment based on imitating macrophages was provided in this study.

DT7 peptide-modified lecithin nanoparticles co-loaded with γ-secretase inhibitor and dexamethasone efficiently inhibit T-cell acute lymphoblastic leukemia and reduce gastrointestinal toxicity.

T-cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy and glucocorticoid resistance is the main recurrent cause for a high relapsed and death rate. Here, we proposed an effective therapeutic regimen of combining gamma-secretase inhibitors (GSIs) with dexamethasone (DEX) to overcome glucocorticoid resistance. Moreover, the bone marrow targeting DT7 peptide-modified lecithin nanoparticles co-loaded with DEX and GSI (TLnp/D&G) were developed to enhance T-ALL cells recognition and endocytosis. In vitro cytotoxicity studies showed that TLnp/D&G significantly inhibited cell survival and promoted apoptosis of T-ALL cells. Mechanically, we found that GSIs promoted DEX-induced cell apoptosis by two main synergetic mechanisms: 1) GSIs significantly upregulated glucocorticoid receptor (GR) expression in T-ALL and restored the glucocorticoid-induced pro-apoptotic response. 2) Both DEX and GSI synergistically inhibited BCL2 and suppressed the survival of T-ALL cells. Furthermore, in vivo studies demonstrated that TLnp/D&G showed high bone marrow accumulation and better antileukemic efficacy both in leukemia bearing models and in systemic Notch1-induced T-ALL models, with excellent biosafety and reduced gastrointestinal toxicity. Overall, our study provides new strategies for the treatment of T-ALL and promising bone marrow targeting systems with high transformation potential.

Comparison of trace element concentrations in freshwater fish and marine fish consumed in Shandong Province, China, and their potential risks to human health.

This study provides the primary data of ten trace element concentrations from four highly consumed cultured freshwater fish species in comparison to six marine fish collected from markets of the Shandong province, China, and evaluates the potential human health risks from consuming these fish. A significant difference in five metal concentrations (Cr, As, Se, Cd, Pb) was found between freshwater and marine fish. With the exception of chromium, the other four element contents in marine fish were higher than those in freshwater fish. According to estimated daily intake (EDI), target hazard quotient (THQ), total target hazard quotient (TTHQ), and the permissible safety limits prescribed by various agencies, consumption of the examined fish species is safe for human health. However, chromium in freshwater fish and arsenic in marine fish should still be a cause for concern in terms of human health, especially for fisher folk communities and populations that frequently consume fish.

Self-assembly of paramagnetic amphiphilic copolymers for synergistic therapy.

Engineering nanoparticles (NPs) with multifunctionality has become a promising strategy for cancer theranostics. Herein, theranostic polymer NPs are fabricated via the assembly of amphiphilic paramagnetic block copolymers (PCL-b-PIEtMn), in which IR-780 and doxorubicin (DOX) were co-encapsulated, for magnetic resonance (MR) and near infrared fluorescence (NIRF) imaging as well as for photo thermal therapy (PTT)-enhanced chemotherapy. The synthesized amphiphilic paramagnetic block copolymers demonstrated high relaxivity (r1 = 7.05 mM-1 s-1). The encapsulated DOX could be released with the trigger of near infrared (NIR) light. In vivo imaging confirmed that the paramagnetic NPs could be accumulated effectively at the tumor sites. Upon the NIR laser irradiation, tumor growth was inhibited by PTT-enhanced chemotherapy. The advantages of the reported system lie in the one-step convergence of multiple functions (i.e., imaging and therapy agents) into a one delivery vehicle and the dual mode imaging-guided synergistic PTT and chemotherapy. This study represents a new drug delivery vehicle of paramagnetic NPs for visualized theranostics.

Promoting Early Diagnosis and Precise Therapy of Hepatocellular Carcinoma by Glypican-3-Targeted Synergistic Chemo-Photothermal Theranostics.

The specific-targeting approach could promote the specificity of diagnosis and the accuracy of cancer treatment. The choice of a specific-targeting receptor is the key step in this approach. Glypican-3 (GPC3) is an oncofetal proteoglycan anchored on the cell membrane. It is overexpressed even in the early stage of hepatocellular carcinoma (HCC), whereas it shows almost no expression in the healthy adult liver. Therefore, GPC3 may be applied as a specific-targeting receptor for HCC theranostics. In this study, a GPC3 specific-targeting theranostics nanodevice, GPC3 targeting peptide (named G12)-modified liposomes co-loaded with sorafenib (SF) and IR780 iodide (IR780), was developed (GSI-Lip), which aims to realize early diagnosis and precise chemo-photothermal therapy of HCC. SF was the first-line chemotherapy drug for the treatment of HCC. IR780 was used for photothermal therapy and near-infrared fluorescence imaging. The evaluation of early diagnosis verified that early-stage tumors (3.45 ± 0.98 mm3, 2 days after 5 × 105 H22 cells' inoculation in mice) could be clearly detected using GSI-Lip, which was significantly more sensitive than folic acid-modified liposomes ( p < 0.01, 32.90 ± 10.01 mm3, 4 days after 1 × 106 H22 cells' inoculation in mice). The study of the endocytic pathway indicated that specific G12/GPC3 recognition may induce caveolae-mediated endocytosis of GSI-Lip. Notably, the accumulation of GSI-Lip in tumors was significantly increased compared with that observed with folic acid-modified liposomes ( p < 0.01). Specific-targeting endowed the precise antitumor effect of GSI-Lip. GSI-Lip showed a higher antitumor efficacy in comparison with folic acid-modified liposomes (inhibition rate: 90.52% vs 84.22%, respectively; p < 0.01). During a period of 21 days, the synergistic chemo-photothermal therapy (GSI-Lip + laser) exhibited a better antitumor effect versus GSI-Lip without laser (inhibition rate: 94.93% vs 90.52%, respectively; p < 0.01). Overall, GPC3-targeted GSI-Lip promoted the sensitivity and specificity of HCC early diagnosis and achieved synergistic efficacy of chemo-photothermal theranostics, which has potential clinical applications. Furthermore, the present study revealed that a more specific-targeting ligand could further improve the efficacy of theranostics against HCC.

Preparation and evaluation of etoposide-loaded lipid-based nanosuspensions for high-dose treatment of lymphoma.

Aim: High-dose administration of etoposide (VP16) was limited by its poor aqueous solubility and severe systemic toxicity on lymphoma therapy. Herein, a novel VP16-loaded lipid-based nanosuspensions (VP16-LNS) was developed for improving drug solubility, enhancing antitumor effect and reducing systemic toxicity. Materials & methods: VP16-LNS with soya lecithin and D-α-tocopheryl PEG 1000 succinate (TPGS) as stabilizers were prepared by nanoprecipitation method. Results: VP16-LNS exhibited uniform spherical morphology, small particle size and favorable colloidal stability. The concentration of VP16 in VP16-LNS was high enough (1017.67 µg/ml) for high-dose therapy on lymphoma. Moreover, VP16-LNS displayed long blood circulation time, selective intratumoral accumulation, remarkable antitumor effect and upregulated safety. Conclusion: VP16-LNS would be an efficient nanoformulation for clinical intravenous application against lymphoma.

Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma.

Non-viral nanocarrier affords a platform for drug and siRNA combination, the focus of which is to load drug and siRNA into a single carrier, allowing for co-delivery and a synergistic effect at tumour site. In our previous study, pH-sensitive carboxymethyl chitosan-modified liposomes (CMCS-SiSf-CL) were assembled for sorafenib (Sf) and Cy3-siRNA co-loaded. The present study evaluated in vitro and in vivo co-delivery of the co-loaded liposomes. Further, in vitro inhibiting hepatocellular carcinoma of the pH-sensitive sorafenib (Sf) and VEGF-siRNA co-loaded liposomes was discussed. The experimental results demonstrated co-delivery and penetration into 2-dimensional (2D) cultured HepG2 cells, 3-dimensional (3D) cultured HepG2 tumour spheroids and tumour regions of H22 tumour-bearing mice. Compared with free siRNA and single loaded carrier, co-delivery liposomes exhibited enhanced VEGF downregulating effect, inducing cell early apoptosis. Therefore, the CMCS-SiSf-CL delivery system can lay the foundation for the co-delivery systems development and provide new area for HCC therapy.

Pseudomonas species isolated from tobacco seed promote root growth and reduce lead contents in Nicotiana tobacum K326.

Endophytic bacteria are generally helpful for plant growth and protection. We isolated from tobacco seeds three Pseudomonas strains (K03, Y04, and N05) that could produce siderophores, indole-3-acetic acid, and 1-aminocyclopropane-1-carboxylate deaminase, fix nitrogen, dissolve phosphorus and potassium, and tolerate heavy metals. In pot experiments, the three isolated strains significantly promoted root growth and increased the root enzyme activity in Nicotiana tobacum K326. Furthermore, bacterial inoculations increased the proportion of residual lead (Pb) by 8.36%-51.63% and decreased the total Pb content by 3.28%-6.38% in the contaminated soil during tobacco planting, compared with uninoculated soils. An effective decrease in Pb content was also found in tobacco leaves with bacterial inoculations. K03 inoculation decreased the Pb content in the upper leaves by 49.80%, and Y04 inoculation had the best effect, decreasing the Pb content in the middle leaves by 70.12%. Additionally, soil pH and root activity had significant effects on transformation and translocation of Pb. The study suggested that in response to Pb pollution in soil, a reasonable application of endophytes (e.g., Pseudomonas) might be a promising approach in promoting tobacco growth and reducing Pb content in tobacco, while simultaneously enhancing Pb stabilization in soils.

Hormesis of mercuric chloride-human serum albumin adduct on N9 microglial cells via the ERK/MAPKs and JAK/STAT3 signaling pathways.

Mercury chloride (HgCl2), a neurotoxicant that cannot penetrate the blood-brain barrier (BBB). Although when the BBB are got damaged by neurodegenerative disorders, the absorbed HgCl2, mainly in form of Hg (II)-serum albumin adduct (Hg-HSA) in human plasma, can penetrate BBB and affect central nervous system (CNS) cells. Current study planned to evaluate the effect of Hg-HSA on the physiological function of N9 microglial cells. At low dosage (15 ng/mL) of Hg-HAS, the observed outcomes was: promoted cell propagation, Nitric Oxide (NO) and intracellular Ca2+ levels enhancement, suppressed the release of TNF-α and IL-1ß and inhibited cell proliferation. At high dosage (15 µg/mL) we observed decline in NO and intracellular Ca2+ levels, and increment in the release of TNF-α and IL-1ß. These biphasic effects are similar to hormesis, and the hormesis, in this case, was executed through ERK/MAPKs and JAK/STAT3 signaling pathways. Study of quantum chemistry revealed that Hg2+ could form stable coordination structures in both Asp249 and Cys34 sites of HSA. Although five-coordination structure in Asp249 site is more stable than four-coordination structure in Cys34 site but four-coordination structure is formed easily in-vivo in consideration of binding-site position in spatial structure of HSA.

[Effects of Tongbi capsule on joint lesions in rabbits with rheumatoid arthritis].

The purpose of this experiment is to observe the effects of Tongbi capsule on joint lesions in rabbit with rheumatoid arthritis induced by ovalbumin and explore the mechanism in order to provide reference for clinical application of Tongbi capsule. Rheumatoid arthritis in rabbits was induced by subcutaneous injection of emulsions of ovalbumin and Freund's complete adjuvant and intra articular injection of ovalbumin. After successful modeling, 30 New Zealand rabbits with arthritis were randomly divided into model control group, the high, medium and low dose groups of Tongbi capsule (90, 45, 22.5 mg·kg⁻¹) and prednisone group (5 mg·kg⁻¹). Another six normal rabbits were used as normal control group. After 24 hours of modeling, the rabbits in Tongbi capsule groups received intragastric (i.g.) administrations of Tongbi capsule at 90, 45, 22.5 mg·kg⁻¹·d⁻¹, and the rabbits of prednisone group received i.g. administrations of prednisone at 5 mg·kg⁻¹·d⁻¹ for 2 weeks. The rabbits in normal and model groups received the same volume of distilled water at the same time. The swelling degree of rabbit knee joint and local skin temperature were observed daily. After two weeks of administration, pathological changes of rabbit knee joint were examined by magnetic resonance imaging (MRI); the morphological changes of articular cartilage and synovial membrane were observed by microscope; and the contents of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme linked immunosorbent assay (ELISA).The results showed that 24 h after modeling, the knee joints of the rabbits were swollen, with red or dark redlocal skin, and fever, elevated local skin temperature and increased diameters of knee joints. Two weeks after modeling, the swelling of rabbit knee joints was obvious in model group; the joint cavities were filled with purulent fluid; joint synovial membranes were obviously thickened, and even joint cavities were fibrotic and cartilage surfaces showed slight defect; the surface of articular cartilage was obvious fibrosis; synovial epithelial cell proliferation was obvious and accompanied by extensive inflammatory cell infiltration; the levels of IL-1 and TNF-α were significantly higher as compared with those seen in model rabbits (P<0.05, P<0.01). After 1 and 2 weeks of administration, knee joint diameters and local skin temperatures were smaller or lower than thosein model group (P<0.05, P<0.01); The lesions of joint cartilage and synovial of all rabbits in each group were less than those in model group; IL-1 and TNF-α levels in serum were also lower than those in model group (P<0.05, P<0.01). The results reveal that high and medium doses of Tongbi capsule can suppress rheumatoid arthritis induced by ovalbumin in rabbits, reduce joint swelling, inhibit synovial epithelial and fiber hyperplasia and inflammatory cell infiltration, and alleviate articular cartilage damage. The mechanism may be associated with decreasing IL-1 and TNF-α levels in serum.

Strengthen effects of dominant strains on aerobic digestion and stabilization of the residual sludge.

In order to strengthen the aerobic digestion of residual sludge, shorten the time of sludge stabilization and further reduce operating costs, 3 dominant strains identified as Pseudomonas sp. L3, Acinetobacter sp. L16 and Bacillus sp. L19 were isolated from long-term aerobic digestion sludge. Results showed that the sludge stabilization time were reduced by 3-4days compared with the control when the dominant strains were added to the process of sludge aerobic digestion. The addition of dominant strains accelerated the accumulation of TOC, nitrate nitrogen and ammonia nitrogen in the digestive solution at different levels, and it was beneficial to the dissolution of phosphorus. Controlling DO 3-5mg/L, pH 6.5, the strains of Pseudomonas sp. L3 and Bacillus sp. L19 were combined dosing with the dosage of 2% in the process of sludge aerobic digestion, compared with the control, digestion rates of TOC and MLSS were increased about 19% and 16%, respectively.

QM/MM studies on the calcium-assisted ß-elimination mechanism of pectate lyase from bacillus subtilis.

Pectate lyase utilizes the anti-ß-elimination chemistry to catalyze the cleavage of α-1,4 glycosidic bond between D -galacturonate regions during the degradation of plant polysaccharide pectin. We report here detailed mechanistic studies of the Bacillus subtilis pectate lyase (BsPel) using QM/MM calculations. It was found that the residue Arg279 serves as the catalytic base to abstract the α-proton from C52 atom of substrate Ada2 subsite, forming an unstable carbanion intermediate. The glycosidic bond of this intermediate is scissile to generate the 4,5-unsaturated digalacturonate product and a negatively charged ß-leaving group. Two active site residues (Lys247 and Arg279) and two Ca2+ ions (Ca2 and Ca3) form hydrogen-bonding and coordination interactions with C52 COO- of Ada2, respectively, which facilitate the proton abstraction and stabilize the generated carbanion intermediates. Arg284 is not the potential proton donor to saturate the leaving group. Actually, the proton source of leaving group is the solvent water molecule rather than any active site acidic residues. In addition, the calculation results suggest that careful selections of QM- and Active-regions are essential to accurately explore the enzymatic reactions. Proteins 2016; 84:1606-1615. © 2016 Wiley Periodicals, Inc.

In vivo biodistribution, biocompatibility, and efficacy of sorafenib-loaded lipid-based nanosuspensions evaluated experimentally in cancer.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In this study, sorafenib-loaded lipid-based nanosuspensions (sorafenib-LNS) were first developed as an intravenous injectable formulation to increase the efficacy of sorafenib against HCC. LNS were used as nanocarriers for sorafenib owing to their desired features in increasing the solubility and dissolution velocity, improving the bioavailability of sorafenib. Sorafenib-LNS were prepared by nanoprecipitation and consisted of spherical particles with a uniform size distribution (164.5 nm, polydispersity index =0.202) and negative zeta potential (-11.0 mV). The drug loading (DL) was 10.55%±0.16%. Sorafenib-LNS showed higher in vitro cytotoxicity than sorafenib against HepG2 cells (P<0.05) and Bel-7402 cells (P<0.05). The in vivo biodistribution, biocompatibility, and antitumor efficacy of sorafenib-LNS were evaluated in H22-bearing liver cancer xenograft murine model. The results showed that sorafenib-LNS (9 mg/kg) exhibited significantly higher antitumor efficacy by reducing the tumor volume compared with the sorafenib oral group (18 mg/kg, P<0.05) and sorafenib injection group (9 mg/kg, P<0.05). Furthermore, the results of the in vivo biodistribution experiments demonstrated that sorafenib-LNS injected into H22 tumor-bearing mice exhibited increased accumulation in the tumor tissue, which was confirmed by in vivo imaging. In the current experimental conditions, sorafenib-LNS did not show significant toxicity both in vitro and in vivo. These results suggest that sorafenib-LNS are a promising nanomedicine for treating HCC.

Sorafenib and gadolinium co-loaded liposomes for drug delivery and MRI-guided HCC treatment.

To improve the poor water solubility of sorafenib and to monitor its distribution and the early feedback effects on its in vivo treatment efficacy in a precise manner, sorafenib (SF) and gadolinium (Gd) co-loaded liposomes (SF/Gd-liposomes) were prepared. The simultaneous imaging and therapy efficacies of the SF/Gd-liposomes were tested. The solubility of SF in SF/Gd-liposomes was significantly increased from 0.21 µg/mL to 250 µg/mL. The imaging capability of SF/Gd-liposomes were tested by in-vitro and the in-vivo imaging ability tests and the results confirmed that SF/Gd-liposomes could be served as an effective contrast agent. The design of SF/Gd-liposomes allowed the MRI-guided in vivo visualization of the delivery and biodistribution of liposome. In the in vivo antitumor studies, SF/Gd-liposomes had better antitumor effects in H22 tumor-bearing mice than SF solution (oral or i.v. administration) (P<0.05). These findings indicated that the SF/Gd-liposomes could be used as the promising nano-carriers for the MRI-guided in vivo visualization of the delivery and HCC treatment.

[A randomized, placebo controlled study on Fangfeng Tongsheng granule in treatment of sub-acute eczema].

The clinical study was conducted to further evaluation the effectiveness and safety of Fangfeng Tongsheng granule in the treatment of sub-acute eczema (superficial cold and interior heat syndrome, exterior and interior sthenic syndrome). In the block randomized, multi-centered study, totally 108 patients were enrolled and assigned to two groups: 72 patients in the test group and 36 patients in the placebo control group. Those in the test group took Fangfeng Tongsheng granule with the dose of 3 g, twice a day, while those in the control group were give simulated agent granules with the same dose. The therapeutic course lasted for 14 days. Their efficacies in TCM syndrome, dermal symptoms and adverse events were observed. According to the test results, except for the one exit case, all of the remaining 108 cases, including 71 in the test group, and 36 in the control group, completed the clinical trial. As for the efficacy of TCM syndrome, after the medication for 2 weeks, the cure rate was 33.81% (24/71) in the test group and 0% (0/36) in the control group (P < 0.01), with a statistical difference between the two groups. Regarding the TCM score, after the medication for 2 weeks, the test group decreased by (12.82 +/- 7.96), while the control group decreased by (3.67 +/- 4.12), indicating a statistical difference between the two groups. As for the efficacy of dermal symptoms, after the medication for 2 weeks, the cure rate was 25.35% (18/71) in the test group and 0% (0/36) in the control group, with a statistical difference between the two groups. Regarding the dermal symptom score, after the medication for 2 weeks., the test group decreased by (10.04 +/- 7.17), while the control group decreased by (2.33 +/- 3.57), indicating a statistical difference between the two groups. There was no significant adverse event caused by Fangfeng Tongsheng granule. In conclusion, Fangfeng Tongsheng granule was effective and safe in treating subcute eczema (superficial cold and interior heat syndrome, exterior and interior sthenic syndrome).

Theranostic Polymeric Micelles for the Diagnosis and Treatment of Hepatocellular Carcinoma.

Theranostics, which combine molecular imaging (diagnostics) and drug delivery (therapeutics) in a single platform, have recently shown great potential in cancer therapy. In this article, a polymeric micelle was designed and prepared for simultaneous magnetic resonance imaging (MRI) and treatment of hepatocellular carcinoma (HCC). Theranostic micelles were assembled using Poly(lactic acid)-poly(ethylene glycol)-poly(L-lysine)-diethylenetriamine pentaacetic acid (PLA-PEG-PLL-DTPA) and PLA-PEG-PLL-Biotin. The HCC therapeutic paclitaxel (PTX) was encapsulated in the cores and Gd ions for imaging were chelated to the DTPA moieties. Biotinylated alpha-fetoprotein (AFP) antibodies were linked to the micelle surface by a biotin-avidin reaction to form targeted Gd/PTX-loaded micelles (TGPM). TGPM were of spherical or ellipsoidal shape with uniform particle size distribution (147.50 ± 4.71 nm), positive zeta potential (24.45 ± 1.04 mV), and high encapsulation efficiency (88.76 ± 1.64%) and drug loading (1.59 ± 0.06%). The cytotoxicity of TGPM in HepG2 cells was superior to that of Taxol or Gd/PTX-loaded micelles (GPM). In MRI tests in vitro, the T1 relaxivity of TGPM was 21.589 mM(-1) s(-1), 4.4 times higher than Magnevist (r1 = 4.8 mM(-1) s(-1)). In H22 tumor-bearing mice, TGPM significantly increased tumor imaging intensity (more than 3 times) and prolonged imaging time (from 1 to 6 h) compared to Magnevist. In vivo, TGPM exhibited higher anti-tumor efficiency than Taxol and GPM. These results indicate that TGPM has great potential in HCC theranostics.

Preclinical studies of N3-O-toluyl-fluorouracil-loaded lipid-based nanosuspensions in H22-bearing mice.

PURPOSE: N3-O-toluyl-fluorouracil (TFU) is a potential antitumor prodrug of 5-fluorouracil (5-FU), but its poor solubility has limited its use in clinic. This study aimed to improve the bioavailability of TFU by preparing TFU-loaded lipid-based nanosuspensions (TFU-LNS) and perform a preclinical evaluation. METHODS: TFU-LNS were prepared through high-pressure homogenization and were lyophilized afterwards. For in vitro test, the physicochemical properties and cytotoxicity against HegG2 cells were conducted. For in vivo evaluation, the pharmacokinetics, tissue distribution, and antitumor efficacy were investigated in H22-bearing Kunming mice. RESULTS: TFU showed different degradability in four media; in particular, nearly all of it converted to an equimolar amount of 5-FU in blank plasma of Wistar rats. The lyophilized TFU-LNS had a mean particle size of 180.03±3.11 nm and zeta potential of -8.02±1.43 mV and showed no discernible changes after storage at 4°C for 3 months. In the in vivo antitumor study, the antitumor efficacy of TFU-LNS was consistent with that of 5-FU injection. Furthermore, TFU-LNS released a lower concentration of 5-FU in heart and kidney throughout the tissue distribution studies. CONCLUSION: TFU-LNS exhibited convincing antitumor activity and easy scale-up opportunity, which suggests that TFU-LNS might be a promising drug delivery system for cancer therapy.