The anti-atherogenic effects of spirulina (Spirulina platensis) were investigated in the New Zealand White (NZW) rabbit model. The animal had hypercholesterolemia induced by being fed a high ...cholesterol diet (HCD) containing 0.5% cholesterol for 4 wk, and then fed a HCD supplemented with 1 or 5% spirulina (SP1 or SP5) for an additional 8 wk. Spirulina supplementation lowered intimal surface of the aorta by 32.2 to 48.3%, compared to HCD. Serum triglyceride (TG) and total cholesterol (TC) significantly were reduced in SP groups. After 8 wk, serum low density lipoprotein cholesterol (LDL-C) remarkably decreased by 26.4% in SP1 and 41.2% in SP5, compared to HCD. On the other hand, high density lipoprotein cholesterol (HDL-C) was markedly increased in SP1 and SP5 compared with that in the HCD group from 2 to 8 wk. These results suggest that spirulina intake can cause the reduction of hypercholesterolemic atherosclerosis, associated with a decrease in levels of serum TC, TG and LDL-C, and an elevation of HDL-C level. Spirulina may, therefore, be beneficial in preventing atherosclerosis and reducing risk factors for cardiovascular diseases.
Optimizing flowering time in crop plants is critical for maximizing yield and quality under target environments. While there is a wide range of heading date variation in Korean rice cultivars, the ...underlying gene mechanisms are unclear. Here, we sequenced the protein coding regions of Hd1, the major rice heading date gene, from 293 Korean rice cultivars and investigated the associations between Hd1 allele types and major agronomic traits under four different environments. There were four functional Hd1 and five nonfunctional hd1 alleles distributed among the 293 Korean rice cultivars. The effects of the Hd1 allele types were highly significant for days to heading in all four environments, explaining 51.4–65.8% of the phenotypic variation. On average, cultivars carrying nonfunctional hd1 headed 13.7 days earlier than those carrying functional Hd1. While the Hd1 allele types exhibited highly significant effects on culm length and protein content under all four environments, the differences between cultivars carrying Hd1 and hd1 were minimal. The effects of the Hd1 allele types on amylose content were significant in only one of the four environments. Our results provide useful information for fine-tuning rice heading dates by utilizing different Hd1 alleles in rice breeding programs.
Topical drug administration to the eye is limited by low drug bioavailability due to its rapid clearance from the preocular surface. Thus, multiple daily administrations are often needed, but patient ...compliance is low, hence a high chance of unsatisfactory treatment of ocular diseases. To resolve this, we propose mucoadhesive microparticles with a nanostructured surface as potential carriers for delivery of brimonidine, an ocular drug for glaucoma treatment. For sustained drug delivery, the microparticles were composed mainly of a diffusion-wall material, poly(lactic-co-glycolic acid) and a mucoadhesive polymer, polyethylene glycol, was used as an additive. Due to their nanostructured surface, the microparticles with a mucoadhesive material exhibited a 13-fold increase in specific surface area and could thus adhere better to the mucous layer on the eye, as compared with the conventional spherical microparticles. When loaded with brimonidine, the mucoadhesive microparticles with a nanostructured surface increased both drug bioavailability and its activity period by a factor of more than 2 over Alphagan P, a marketed eye drop of brimonidine.
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We investigated whether oral administration of curcumin suppressed type II collagen–induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 ...production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-α–stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cδ (PKCδ) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCδ and the JNK/c-Jun signaling pathway.
A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo ...study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step hydrothermal reaction and ion-exchange reaction. The MTX-LDH was determined to have a neutral surface charge and strong agglomeration in the neutral aqueous condition due to the surface adsorbed MTX; however, the existence of proteins in the media dramatically reduced agglomeration, resulting in the hydrodynamic radius of MTX-LDH being similar to the primary particle size. The protein fluorescence quenching assay exhibited that MTX readily reduced the fluorescence of proteins, suggesting that the interaction between MTX and proteins was strong. On the other hand, MTX-LDH showed much less binding constant to proteins compared with MTX, implying that the protein interaction of MTX was effectively blocked by the LDH carrier. The in vivo hemolysis assay after intravenous injection of MTX-LDH showed neither significant reduction in red blood cell number nor membrane damage. Furthermore, the morphology of red blood cells in a mouse model did not change upon MTX-LDH injection. Scanning electron microscopy showed that the MTX-LDH particles were attached on the blood cells without serious denaturation of cellular morphology, taking advantage of the cell hitchhiking property.
Despite advancements in heart transplantation for pediatric patients in Korea, the waiting list mortality has not been reported. Therefore, we investigated the waiting list mortality rate and factors ...associated with patient mortality.
We reviewed the medical records of pediatric patients who were registered for heart transplantation at three major hospitals in Korea from January 2000 to January 2020. All patients who died while waiting for heart transplantation were investigated, and we identified the waiting list mortality rate, causes of mortality and median survival periods depending on the variable risk factors.
A total of 145 patients received heart transplantations at the three institutions we surveyed, and the waiting list mortality rate was 26%. The most common underlying diseases were cardiomyopathy (66.7%) and congenital heart disease (30.3%). The leading causes that contributed to death were heart failure (36.3%), multi-organ failure (27.2%), and complications associated with extracorporeal membrane oxygenation (ECMO) (25.7%). The median survival period was 63 days. ECMO was applied in 30 patients. The different waiting list mortality percentages according to age, cardiac diagnosis, use of ECMO, and initial Korean Network of Organ Sharing (KONOS) level were determined using univariate analysis, but age was the only significant factor associated with waiting list mortality based on a multivariate analysis.
The waiting list mortality of pediatric heart transplantation candidates was confirmed to be considerably high, and age, underlying disease, the application of ECMO, and the initial KONOS level were the factors that influenced the survival period.
Wrinkles, one of the most common signs of aging, are primarily caused by the continuous contraction of muscles. Muscle contraction is induced by the binding of acetylcholine (ACh), released at the ...neuromuscular junction, to nicotinic acetylcholine receptor (nAChR) present on the muscle cell surface. In this study, we aimed to develop a wrinkle-improving peptide that inhibits the binding of ACh to nAChR using peptide phage display technology. Our peptide showed a remarkably high binding affinity to nAChR subunit α1, with a value below 1 µM, and was found to inhibit the action of ACh through its interaction with these receptors. Furthermore, it increased collagen synthesis in skin cells and upregulated the expression of the aquaporin-3 (AQP3) and hyaluronan synthase-2 (HAS2) genes. These results confirm that the peptide effectively inhibits muscle contraction and enhances skin elasticity and hydration, contributing to its wrinkle-reducing effects. Clinical studies on humans observed significant improvement in wrinkles after three weeks of use, with substantial reduction observed after six weeks. In conclusion, these findings demonstrate the efficacy of the peptide (named Medipep) in reducing wrinkles.
Background Activation of mast cells through the high-affinity receptor for IgE (FcεRI) underlies atopic allergic reactions. Curcumin can block this activation, but the mechanism and the effects of ...curcumin on IgE-mediated allergic reactions are unknown. Objectives We sought to determine the antiallergic activity of curcumin in vivo and its mechanism of action in mast cells. Methods The antiallergic activity of curcumin was evaluated in mast cell cultures and the passive cutaneous anaphylaxis model. The effects of curcumin on mast cell signaling events were examined by using immunoblotting, immunoprecipitation, RT-PCR, and other molecular biologic approaches. Results Curcumin inhibited antigen-mediated activation of mast cells and passive cutaneous anaphylaxis in mice. Suppression of degranulation and secretion of TNF-α and IL-4 was apparent at concentrations as low as 3 μmol/L curcumin in activated mast cells. Similar concentrations of curcumin suppressed Syk-dependent phosphorylations of the adaptor proteins linker of activated T cells and Grb2-associated binder 2, which are critical for mast cell activation. Although curcumin did not inhibit the phosphorylation of Syk itself, it directly inhibited Syk kinase activity in vitro . Further downstream, activating phosphorylations of Akt and the mitogen-activated protein kinases p38, p44/42 (extracellular signal-regulated kinase 1/2), and c-Jun N-terminal kinase, which are critical for the production of inflammatory cytokines, were also inhibited. Conclusions Curcumin inhibits Syk kinase–dependent signaling events in mast cells and might thus contribute to its antiallergic activity. Therefore curcumin might be useful for the treatment of mast cell–related immediate and delayed allergic diseases.
Nrf2 plays a role in protection of cells against oxidative stress and xenobiotic damage by regulating cytoprotective genes. In this study, we investigated the effect of Nrf2 on melanogenesis in ...normal human melanocytes (NHMCs). When NHMCs were transduced with a recombinant adenovirus expressing Nrf2, melanin synthesis was significantly decreased. Consistent with this result, overexpression of Nrf2 decreased the expression of tyrosinase and tyrosinase-related protein 1. The inhibitory effect of Nrf2 was reversed by overexpression of Keap1, an intracellular regulator of Nrf2. Interestingly, Nrf2 overexpression resulted in marked activation of PI3K/Akt signaling. Conversely, inhibition of PI3K activity by treatment with wortmannin reversed the depigmentary effects of Nrf2. Taken together, these results strongly suggest that Nrf2 negatively regulates melanogenesis by modulating the PI3K/Akt signaling pathway.
To evaluate the influence of topographic profiles (i.e., inner directional angle and angular width) of localized retinal nerve fiber layer (RNFL) defects on the diagnostic performance of macular ...ganglion cell-inner plexiform layer (GCIPL) thickness in discriminating preperimetric glaucoma (PPG) eyes from normal control eyes.
The ganglion cell analysis algorithm in Cirrus OCT was performed to determine the macular GCIPL thickness. Areas under the receiver operating characteristic curves (AUROCs) and the sensitivities/specificities based on an internal normative database were evaluated. The effect of the inner directional angle and the angular width of localized RNFL defects on the diagnostic performance of macular GCIPL parameters were evaluated by using linear-by-linear association analysis and logistic regression analysis.
Ninety-two patients with PPG and 92 age-matched healthy control subjects were enrolled in this study. The AUROC of the best parameters in macular GCIPL was 0.823 (inferotemporal sector), which showed no significant difference in comparison to the best parameters of peripapillary RNFL (7 o'clock sector, 0.764) and optic nerve head (rim area, 0.767) (for all comparisons, P > 0.05). A significant linear association was observed between the inner directional angle of RNFL defects and the sensitivity of macular GCIPL parameters for detecting RNFL defects. The angular width of RNFL defects was not significantly associated with the sensitivity of macular GCIPL parameters.
The diagnostic ability of macular GCIPL parameters was comparable to that of peripapillary RNFL and ONH parameters in PPG. The inner directional angle of RNFL defects, but not the angular width, affects the diagnostic sensitivity of macular GCIPL parameters.
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