Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases.

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

Structural transition of reverse cylindrical micelles to reverse vesicles by mixtures of lecithin and inorganic salts.

HYPOTHESIS: The transformation from reverse micelles to reverse vesicles is influenced by electrostatic interactions between lecithin headgroups and inorganic salts. The electrostatic interactions are expected to influence molecular geometry of lecithin, resulting in a reduction in critical packing parameter (p). Hence, it should be possible to drive structural transitions of reverse self-assembled structures by addition of inorganic salts to lecithin solutions. EXPERIMENTS: Structural transitions of reverse micelles and reverse vesicles were formulated including lecithin and inorganic salts as a function of concentration in cyclohexane. A systematic study was performed using inorganic salts with the different valences of the cations such as Li+, Ca2+, and La3+. To probe the nanodomain structures from the lecithin/salt mixtures, small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) were used. FINDINGS: Adding salts to lecithin solutions induced the systematic transformation of reverse self-assembled structures from reverse spherical micelles to reverse cylindrical micelles and finally to reverse vesicles. The transformation was also correlated with interactions between lecithin headgroups and salts, that is, Li+ < Ca2+ < La3+. In addition, a water-soluble dye such as rhodamine B (RB) can be readily encapsulated into reverse micelles and vesicles, indicating that they are potentially useful for controlled solute delivery.

Incidence and Risk Factors for Blindness in Uveitis: A Nationwide Cohort Study from 2002 to 2013.

Purpose: To investigate the incidence and risk factors of blindness in uveitis.Methods: From a national sample cohort (n = 1,025,340), we selected 9,036 new-onset uveitis patients. Incidences of unilateral and bilateral blindness (visual acuities ≤20/400) were estimated and socioeconomic and clinical risk factors for unilateral blindness in uveitis patients were identified.Result: Incidence of unilateral and bilateral blindness was 2.93 and 0.42 per 1,000 person-years, respectively. The risk factors for unilateral blindness were age >40 (hazard ratio [HR], 2.77, 95% CI [confidence interval], 1.11-6.92) and low household income (HR, 1.50; 95% CI, 1.02-1.98) in uveitis overall, and Behçet's disease (HR, 4.49; 95% CI, 1.59-12.71) in non-anterior uveitis, respectively.Conclusions: Low household income and Behçet's disease influence the risk of blindness in uveitis patients. These findings will help in assessing blindness-related socioeconomic burdens and planning health-care strategies for uveitis patients.

Magnesium supplementation reduces postoperative arrhythmias after cardiopulmonary bypass in pediatrics: a metaanalysis of randomized controlled trials.

Postoperative arrhythmia (POA) is the most common complication encountered after cardiopulmonary bypass (CPB). The preventive effect of magnesium in POA has been confirmed by metaanalyses in adults, but less is known in pediatric patients. A metaanalysis of published trials was conducted to examine the efficacy of magnesium supplementation in POA prevention among pediatric patients undergoing CPB. Relevant trials were identified from electronic databases (Medline, Embase, Web of Science, and Cochrane library). Pooled relative risk (RR) and 95 % confidence intervals (CI) were calculated using Mantel-Haenszel random-effects models, and heterogeneity was determined qualitatively according to I (2) and chi-squared statistical analyses. Among 121 potentially relevant studies, five randomized controlled trials met the inclusion criteria, resulting in a pooled total of 348 participants. Compared with placebo, magnesium supplementation decreased the incidence of arrhythmia after CPB in pediatric patients by 66 % (RR, 0.34; 95 % CI, 0.18-0.65; P = 0.001), with no heterogeneity between trials (heterogeneity P = 0.68; I (2) = 0 %). Magnesium supplementation significantly reduces the incidence of postoperative arrhythmias in pediatric patients undergoing CPB. Although the findings encourage the use of magnesium as an alternative to postoperative arrhythmias after CPB in pediatric patients, higher-quality randomized clinical trials are necessary before the findings can be generalized.

The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica reduces obesity via skeletal muscle AMPK and PPARα.

CONTEXT: Since AMP-activated protein kinase (AMPK) activation in skeletal muscle of obese rodents stimulates fatty acid oxidation, it is reasonable to hypothesize that pharmacological activation of AMPK might be of therapeutic benefit in obesity. OBJECTIVE: To investigate the effects of the traditional Korean anti-obesity drug GGEx18, a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), on obesity and the involvement of AMPK in this process. MATERIALS AND METHODS: After high fat diet-induced obese mice were treated with GGEx18, we studied the effects of GGEx18 on body weight, fat mass, skeletal muscle lipid accumulation, and the expressions of AMPK, peroxisome proliferator-activated receptor ά (PPARα), and PPARα target genes. The effects of GGEx18 and/or the AMPK inhibitor compound C on lipid accumulation and expression of the above genes were measured in C2C12 skeletal muscle cells. RESULTS: Administration of GGEx18 to obese mice for 9 weeks significantly (p < 0.05) decreased body and adipose tissue weights compared with obese control mice (p < 0.05). Lipid accumulation in skeletal muscle was inhibited by GGEx18. GGEx18 significantly (p < 0.05) increased skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, GGEx18 inhibited lipid accumulation, and similar activation of genes was observed in GGEx18-treated C2C12 cells. However, compound C inhibited these effects in C2C12 cells. DISCUSSION AND CONCLUSION: These results suggest that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation.

The Korean traditional medicine gyeongshingangjeehwan inhibits adipocyte hypertrophy and visceral adipose tissue accumulation by activating PPARalpha actions in rat white adipose tissues.

AIM OF THE STUDY: Gyeongshingangjeehwan (GGEx), which is a polyherbal drug composed of four medicinal plants, has traditionally been used as anti-obesity drug in Korean local clinics. Thus, we investigated the effects of GGEx on visceral adiposity and examined whether adipose peroxisome proliferator-activated receptor alpha (PPARalpha) activation is involved in this process. MATERIALS AND METHODS: After Obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and differentiated 3T3-L1 adipocytes were treated with GGEx, we studied the effects of GGEx on not only visceral white adipose tissue (WAT) mass and adipocyte size, but also the expression of adipocyte marker and PPARalpha target genes. RESULTS: Administration of GGEx to obese rats for 8 weeks decreased visceral WAT weight by 30% and the size of adipocytes in mesenteric WAT by 31% without weight changes of other organs. Concomitantly, GGEx increased mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation in mesenteric WAT whereas decreased mRNA expression of adipocyte markers, such as PPARgamma, aP2 and leptin. Serological studies demonstrated that plasma levels of free fatty acids and triglycerides as well as insulin and glucose were decreased following GGEx treatment. Consistent with the in vivo data, GGEx increased PPARalpha reporter gene activity and induced the mRNA expression of PPARalpha target genes involved in mitochondrial fatty acid beta-oxidation in 3T3-L1 cells. GGEx also inhibited triglyceride accumulation in these cells. CONCLUSION: These results suggest that GGEx promotes the reductions in visceral fat mass and adipocyte size in obese animals, and that this event may be mediated by adipose PPARalpha activation.

A facile route for creating "reverse" vesicles: insights into "reverse" self-assembly in organic liquids.

Reverse vesicles are spherical containers in organic liquids (oils) consisting of an oily core surrounded by a reverse bilayer. They are the organic counterparts to vesicles in aqueous solution and could potentially find analogous uses in encapsulation and controlled release. However, few examples of robust reverse vesicles have been reported, and general guidelines for their formation do not exist. We present a new route for forming stable unilamellar reverse vesicles in nonpolar organic liquids, such as cyclohexane and n-hexane. The recipe involves mixing short- and long-chain lipids (lecithins) with a trace of a salt such as sodium chloride. The ratio of short- to long-chain lecithin controls the type and size of self-assembled structure. As this ratio is increased, a spontaneous transition from reverse micelles to reverse vesicles occurs. Small-angle neutron scattering (SANS) and transmission electron microscopy (TEM) confirm the presence of unilamellar vesicles in the corresponding solutions. Average vesicle diameters can be tuned from 60 to 250 nm depending on the sample composition.