Photodynamic Treatment of Colorectal Cancer Using Chlorin e6-Loaded Poly(lactide-co-glycolide)- Based Nanoparticles.

We prepared poly(lactide-co-glycolide) (PLGA) encapsulated with chlorin e6 (Ce6) in an effort to increase the stability and efficiency of photosensitizers for photodynamic therapy (PDT). We determined that Ce6-loaded PLGA nanoparticles (PLGA-Ce6 NPs) had drug-loading efficiency of 5%. The efficiency of encapsulation was 82%, the zeta potential was- 25 mV, and the average diameter was 130 nm. The encapsulation of Ce6 in PLGA nanoparticles showed excellent stability. The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced uptake of the nanoparticles. An in vitro anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC50 value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs penetrated more profoundly and had better phototoxicity than pure drugs. These findings suggest that PLGA-Ce6 NPs might serve as PDT for colorectal cancer.

Influences of surface material on the fire behaviors of two-layer combustibles under autoignition conditions.

Upholstered furniture usually has a typical two-layer structure with an ultra-thin surface layer. The surface layer can significantly affect the overall fire behaviors of the upholstered furniture. A series of experiments were carried out to investigate the fire behaviors of six two-layer combustibles based on a cone calorimeter. An empirical model was proposed to predict the heat release rate of two-layer combustibles. The predictions of the model are fitting quite well with experimental data. It was also known that the ignition time of the two-layer combustis dbles is controlled by those surface fabric materials. The shrink rate and the properties of the residues of those surface fabrics show obvious influences on the combustion processes. Comparing to those uncovered natural latex foam samples, it was known that the peak heat release rate decreases about 26.9% and 11.7% for the samples with natural and synthetic species covers, respectively; and the duration of the burning process increases about 41.7% and 15.4%, respectively. A combustion factor was proposed and a heat transfer model was developed to reflect the contribution of the surface and the second layers to the combustion processes. The combustion factor is within 0.7-0.9 for the six types of surface fabrics.

Molecular mechanism of the role of carbamyl erythropoietin in treating diabetic retinopathy rats.

The aim of the present study was to investigate the therapeutic effects of carbamyl erythropoietin (CEPO) and safflor yellow (SY) in the treatment of rats with diabetic retinopathy (DR) as well as exploring the mechanism of action. Male SD rats were used to establish a diabetes model and streptozotocin-induced retinopathy was also performed in rats. A total of 126 rats with DR were obtained, and model rats were randomly divided into the model (n=42), experimental (n=42) and control (n=42) groups. The rats in the model group were injected with saline, the rats in the experimental group were treated with CEPO, and the rats in the control group were treated with SY. After treatment for 2 weeks, the retinas were harvested for quantitative analysis of the mRNA expression levels of angiogenesis-promoting and -inhibiting molecules, apoptosis-promoting and -inhibiting molecules, and oxidative stress pathway-related factors by Reverse transcription-quantitative PCR (RT-qPCR). No significant differences in expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin (Ang-1), tissue kallikrein (TKLK) and pigment epithelium-derived factor (PEDF) were observed between the experimental and model groups (P>0.05). The expression levels of apoptosis-promoting molecules Bcl-2 related X protein (Bax) and cysteine aspartate specific protease (caspase-3) mRNA in the retina of the experimental group was significantly lower than those in the control group (P<0.05). The expression levels of Bcl-2 and survivin mRNA were significantly higher in the experimental group than in the control group (P<0.05). The expression levels of the oxidative stress pathway nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA were significantly higher in the experimental group than in the control group. Therefore, the therapeutic effects of CEPO in treating DR are better than those of SY. As a result, CEPO may inhibit apoptosis and oxidative stress damage of retinal tissue cells in DR rats without affecting angiogenesis.

Effects of a novel curcumin derivative on the functions of kidney in streptozotocin-induced type 2 diabetic rats.

OBJECTIVE: B6, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6 on diabetic nephropathy and the related mechanisms. MATERIALS AND METHODS: The effects of B6 were studied on fast-blood glucose, serum creatinine, urea nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin. RESULTS: The results showed that B6 treatment could reduce serum creatinine, urea nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal pathological changes in diabetic rats and increase the levels of ACE2 and ACE2 mRNA. CONCLUSION: These results suggested B6 could protect the renal function of diabetic rats. This study provided scientific basis for the further researches and clinical applications of B6.

Effects of puerarin on the retina and STAT3 expression in diabetic rats.

The effects of puerarin on electroretinogram, oxidative stress and STAT3 expression were determined, in diabetic rat retina and serum. Forty Sprague-Dawley rats were randomly divided into the normal control (NC), the diabetic model (DM), the low dose (250 mg/kg) puerarin (LP) or the high dose (500 mg/kg) puerarin group (HP). A diabetic rat model was induced by streptozotocin and animals were continuously treated for 4 weeks; fasting blood glucose was measured at 2 and 4 weeks after modeling. An electroretinogram and serum and tissue levels of glucose, insulin, superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were measured; real-time PCR and ELISA were used to determine STAT3 mRNA and protein expression, respectively, from the retina. The blood glucose and insulin levels in the puerarin groups were significantly lower and higher, respectively than that in the DM group. The amplitude of b-wave of electroretinogram in the DM and the LP groups was significantly lower than that in the NC group; in the LP and HP groups it was significantly higher than the DM group. The serum and retinal tissue activity of SOD and MDA was significantly lower and higher, respectively, in the DM group compared to the NC group; both the LP and HP groups had significantly higher SOD and lower MDA than the DM group. The levels of STAT3 mRNA and protein levels in the DM, LP and HP groups were significantly higher than the NC group; and levels of STAT3 mRNA and protein expression were significantly lower in the LP and HP groups than the DM group. In summary, puerarin can reduce the oxidative stress damage of the retina, and its mechanism is related to the inhibition of STAT3 expression.

In vitro and in vivo drug-drug interaction of losartan and glimepiride in rats and its possible mechanism.

BACKGROUND: Losartan and glimepiride are commonly used drugs to treat chronic diseases of hypertension and diabetes; they are both substrates of CYP2C9. The aim of the present study was to investigate the possible interaction of losartan and glimepiride both in vitro (rat liver microsomes) and in vivo (healthy Sprague-Dawley rats). METHODS: In rat liver microsomes, 1-10 µmol/l losartan and glimepiride were coincubated, and the inhibitory effect was analyzed. In the subsequent pharmacokinetic study, 15 healthy Sprague-Dawley rats received administrations of 5 mg/kg losartan or 1 mg/kg glimepiride or a coadministration. RESULTS: In the rat liver microsome system, glimepiride showed a slight inhibition of losartan at concentrations of 1-10 µmol/l, whereas losartan exhibited no inhibitory effect on glimepiride. In vivo, glimepiride did not modify the plasma concentration of losartan and its metabolite E-3174. The alteration of an increased AUC and Cmax was observed in the pharmacokinetic parameters of glimepiride and hydroxy glimepiride. CONCLUSIONS: Glimepiride did not affect losartan pharmacokinetics in rats, while losartan potently altered glimepiride metabolism; this result was inconsistent with the in vitro outcome. The mechanism requires further investigation. In clinical settings, attention should be paid to the interaction of these two drugs in the human body as well as the possible adverse reactions of glimepiride.

Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors.

Monoamine oxidase-B (MAO-B) inhibitor has been used as neuroprotectants to treat the motor deficits of Parkinson's disease (PD). We designed and synthesized a class of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. The compounds have various inhibitory effects, with compound 6a having a K(i) value of 0.26 µM. Their promising activity in vitro suggests potential use in the treatment of PD.