Core-shell structure of Fe3O4@MTX-LDH/Au NPs for cancer therapy.

Nearly monodispersed magnetic Fe3O4@MTX-LDH/Au nanoparticles (NPs) containing the anticancer agent of methotrexate (MTX) were prepared via a coprecipitation-electrostatic interaction strategy. Firstly, layered double hydroxide (LDH) materials were deposited over the surface of Fe3O4 NPs by the coprecipitation method. Secondly, Au NPs were successfully conjugated onto the surface of LDH through electrostatic interaction. Herein, MTX was used both as the agent for surface modification and the anticancer drug for chemotherapy. These particles presented well-defined core-shell structure, strong magnetization and a high drug-loading capacity. Furthermore, the combined treatment of cancer cells by using Fe3O4@MTX-LDH/Au for synergistic hyperthermia ablation and chemotherapy was demonstrated to exhibit higher therapeutic efficacy than either single treatment alone, underscoring the great potential of the platform for cancer therapy.

Induction of Au-methotrexate conjugates by sugar molecules: production, assembly mechanism, and bioassay studies.

Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose, dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively. Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those doped with dextran and sucrose, therefore potentially presenting a promising treatment platform for anticancer therapy. Based on the present study, this work may provide the first example of using biocompatible sugars as regulating agents to effectively guide the shape and assembly behavior of Au-MTX conjugates. Potentially, the synergistic strategy of drug molecules and sugar molecules may offer the possibility to create more gold-based nanocarriers with new shapes and beneficial features for advanced anticancer therapy.

Novel morphologies of poly(allyamine hydrochloride)-methotrexate nanoassemblies for methotrexate delivery.

Poly(allylamine hydrochloride)-methotrexate (PAH-MTX) nanoassemblies with novel morphologies (i.e. nanostrips, nanorolls, nanosheets, and nanospheres) were achieved for the first time via supramolecular self-assembly directed by the synergistic action of various non-covalent interactions between PAH and MTX molecules in aqueous solution. Herein, MTX acted in a versatile manner as both a morphology-regulating agent and a small molecular hydrophobic anticancer drug. Moreover, different morphologies presented diverse drug release profiles, which may be caused by the distinctive interactions between PAH and MTX molecules. Synergistically non-covalent interactions, including electrostatic interactions, van der Waals forces, and hydrogen bonding, favored easier matrix corrosion and more rapid drug release of non-spherical structures (i.e. nanostrips, nanorolls, and nanosheets) through the ligand exchange process. On the other hand, the highly sealed encapsulation mode for hydrophobic MTX molecules made the nanospheres exhibit slower and better controlled release. In addition, in vitro bioassay tests showed that nanostrips displayed the most obvious suppression on the viability of cancer cells among other morphologies, especially after a longer duration. The strategy of using small molecular anticancer drugs not as passively delivered cargoes but as effective molecular building blocks, opens up a new way to develop self-delivering drugs for anticancer therapy.

Novel morphology change of Au-Methotrexate conjugates: From nanochains to discrete nanoparticles.

A novel morphology change of Au-methotrexate (Au-MTX) conjugates that could transform from nanochains to discrete nanoparticles was achieved by a simple, one-pot, and hydrothermal growth method. Herein, MTX was used efficiently as a complex-forming agent, reducing agent, capping agent, and importantly a targeting anticancer drug. The formation mechanism suggested a similarity with the molecular imprinting technology. The Au-MTX complex induced the MTX molecules to selectively adsorb on different crystal facets of gold nanoparticles (AuNPs) and then formed gold nanospheres. Moreover, the abundantly binding MTX molecules promoted directional alignment of these gold nanospheres to further form nanochains. More interestingly, the linear structures gradually changed into discrete nanoparticles by adding different amount of ethylene diamine tetra (methylene phosphonic acid) (EDTMPA) into the initial reaction solution, which likely arose from the strong electrostatic effect of the negatively charged phosphonic acid groups. Compared with the as-prepared nanochains, the resultant discrete nanoparticles showed almost equal drug loading capacity but with higher drug release control, colloidal stability, and in vitro anticancer activity.

[Effects of nutritional condition on the competitive parameters of Prorocentrum donghaiense and Skeletonema costatum].

By the methods of pure culture and mixed culture in laboratory, this paper studied the effects of different substrate nitrogen and phosphorus concentrations on the population growth and interspecific competitive parameters of two kinds of microalgae, Skeletonema costatum and Prorocentrum donghaiens. With the increasing concentrations of substrate nitrogen and phosphorus, the maximum biomass of the two kinds of microalgae increased, and their specific growth rate was higher in pure culture than in mixed culture. In mixed culture, S. costatum was dominant at the beginning, while P. donghaiense became dominant later. The time period when this change happened was related to the nutritional conditions, and the inflection point for S. costatum and P. donghaiense was about 0-2.6 and 0.5-4.9 d, respectively. Under the test nutritional conditions, the competitive parameter of P. donghaiense to S. costatum (beta) was higher than that of S. costatum to P. donghaiense (alpha). When the substrate nitrogen and phosphorous concentrations were 128 micromol N x L(-1) and 32 micromol P x L(-1), the competitive capability of P. donghaiense was 3.8 times of that of S. costatum, presenting the most obvious difference.

[Expression of connective tissue growth factor in renal interstitial fibrosis after ureteral obstruction and effects of rapamycin thereupon: experiment with rats].

OBJECTIVE: Is a common feature of progressive renal diseases regardless of the initiating insult To clarify the role of connective tissue growth factor (CTGF) in after (UUO) in renal interstitial fibrosis and effects of rapamycin (RAP) thereupon. METHODS: Eighteen Sprague-Dawley rats were randomly divided into 3 equal groups: unilateral ureteral obstruction (UUO) model group, undergoing ligation of the left ureter; RAP treatment group, undergoing ligation of the left ureter and intraperitoneal injection of RAP 0.04 mg.kg(-1).d(-1); and sham operation group. The right kidneys were taken out 7 and 14 days after the operation respectively to undergo renal pathological examination by Masson staining. Semi-quantitative RT-PCR was used to detect the mRNA expression of CTGF. Western blotting was performed to examine the protein expression of CTGF and fibronectin (FN). RESULTS: In comparison with the sham operation group, renal interstitial fibrosis was significant more expression in the 2 UUO groups, especially the UUO model group (P < 0.01). Seven and 14 days after the operation the levels of CTGF mRNA expression of the UUO model and RAP treatment groups (both P < 0.01), and the level of CTGF mRNA expression of the RAP treatment group was significantly lower than that of the UUO model group (P < 0.01), however, there was no significant difference in the level of CTGF mRNA expression between the 2 UUO groups 14 days after the operation. Seven and 14 days after the operation the levels of CTGF protein expression of the UUO model and RAP treatment groups were both significantly higher than that of the sham operation group (both P < 0.01), and the levels of CTGF protein expression of the RAP treatment group were significantly lower than that of the UUO model group (P < 0.05 and P < 0.01). The levels of FN expression 7 and 14 days after the operation of the 2 UUO groups were both significantly higher than that of the sham operation group (both P < 0.01). and the level of FN expression 7 days after of the RAP treatment group was significantly lower than that of the UUO model group (P < 0.01), however, there was no significant difference in the level of FN expression between the 2 UUO groups 14 days after the operation. CONCLUSION: The expression of CTGF mRNA and that of CTGF protein increase after UUO. Rapamycin play a protective role in the kidney by downregulating the CTGF expression and alleviating the renal interstitial fibrosis following UUO.

Effect of compound glycyrrhizin injection on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment.

OBJECTIVE: To investigate the effects of Compound Glycyrrhizin Injection (CGI) on liver function and cellular immunity of children with infectious mononucleosis complicated liver impairment (IM-LI) and to explore its clinical therapeutic effect. METHODS: Forty-two patients with IM-LI were randomly assigned, according to the randomizing number table, to two groups, 20 in the control group and 22 in the treated group. All the patients were treated with conventional treatment, but to those in the treated group, CGI was given additionally once a day, at the dosage of 10 ml for children aged below 2 years, 20 ml for 2-4 years old, 30 ml for 5-7 years old and 40 ml for 8- 12 years old, in 100-200 ml of 5% glucose solution by intravenous dripping. The treatment lasted for 2 weeks. T lymphocyte subsets and serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected before and after treatment. Besides, a normal control group consisting of 20 healthy children was also set up. RESULTS: Baseline of the percentage of CD3 + , CD8 + lymphocyte and serum levels of ALT, AST, TBiL in the children with IM-LI were markedly higher, while the percentage of CD4 + lymphocyte and the CD4 + /CD8 + ratio was markedly lower in IM-LI children as compared with the corresponding indices in the healthy children ( P<0.01). These indices were improved after treatment in both groups of patients, but the improvement in the treated group was better than that in the control group (P<0.01). CONCLUSION: Cellular immunity dysfunction often occurs in patients with IM-LI, and CGI treatment can not only obviously promote the recovery of liver function, but also regulate the immune function in organism.

[Maternal plasma leptin levels and their relationship to insulin and glucose in pregnant women with gestational diabetes mellitus and gestational impaired glucose tolerance].

OBJECTIVE: To investigate the changes in leptin levels and the relationship between the substance and insulin and glucose in pregnant women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: Radio immunoassay was used to measure the leptin levels at fasting and 3 h after oral glucose load (50 g) in 36 patients with GDM and GIGT, and also in 24 normal pregnant women. In each pregnant women, fasting serum insulin levels and glycosylated haemoglobin values were measured by electrochemiluminescent immunoassays and pressure liquid chromatography (LPLC) respectively, glucose levels 1 h after the administration of glucose by glucose oxidase method. RESULTS: The serum leptin levels in pregnant women with GDM and GIGT and normal pregnant women were (14.9 +/- 4.3) micro g/L and (10.0 +/- 1.8) micro g/L, respectively, suggesting the serum leptin levels were significantly higher in pregnant women with GDM and GIGT than in normal controls. The levels of fasting serum insulin, glycosylated haemoglobin values and plasma glucose levels obtained 1h after oral administration of 50 g glucose were (12.9 +/- 4.3) mU/L, (6.1 +/- 1.1)%, (11.0 +/- 1.4) mmol/L, respectively, whereas the corresponding values in normal controls were (8.6 +/- 3.2) mU/L, (4.5 +/- 1.0)%, (7.8 +/- 1.2) mmol/L. A positive correlation was found between maternal serum leptin levels and fasting serum insulin levels in pregnant women with GDM and GIGT (r = 0.835, P < 0.01). A positive correlation was also found between maternal leptin concentrations and glycosylated haemoglobin values, as well as between leptin levels and plasma glucose levels obtained 1 h after the administration of 50g glucose in women with GDM and GIGT (r = 0.758, P < 0.01; r = 0.561, P < 0.01). CONCLUSIONS: Leptin levels are elevated in pregnant women with GDM and GIGT compared with healthy pregnant women, a positive and significant correlation was found between the maternal leptin levels and fasting insulin levels, as well as between the maternal leptin levels and plasma glucose levels obtained 1 h after the administration of 50 g glucose in women with GDM and GIGT.