Biodegradable membranes for the controlled release of progesterone. 1. Characterization of membrane morphologies coagulated from PLGA/progesterone/DMF solutions

Biodegradable membranes containing progesterone as a drug were prepared from ternary, poly(d,l‐lactide‐co‐glycolide)/progesterone/dimethylformamide, solutions. The homogeneous solutions, after cast on glass plates, were solidified to result in a solid membrane structure by three different solvent‐removal processes: solvent evaporation under vacuum, solvent extraction via immersion into the nonsolvent bath, or vapor exposure at high humidity condition. Impregnation characteristics of progesterone in the prepared membranes varied significantly, depending on the removal processes used. When a cast solution was solidified by exposure at the environment of 70% relative humidity, progesterone was separated from a membrane structure with the morphology of flake‐like shapes, and thermal analysis of the prepared membrane showed the clear, endothermic peak of the drug. Vitrification of a cast solution by solvent evaporation under vacuum induces both the uniform drug dispersion in the polymer matrix, with the drug forming spherical structures, and the strong interaction between the drug and the matrix, as identified by a broadened melting endotherm of the drug. When coagulated at thermodynamic nonequilibrium conditions through rapid exchange between dimethyformamide and water, the cast solution film results in a membrane structure consisting of the drug distributed nonuniformly in the polymer matrix. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 60–67, 2000     

Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone demethylase KDM7A in the development of hepatic steatosis. KDM7A overexpression in AML12 cells upregulated diacylglycerol acyltransferase 2 (DGAT2) expression and resulted in increased intracellular triglyceride (TG) accumulation. Conversely, KDM7A knockdown reduced DGAT2 expression and TG accumulation, and significantly reversed free fatty acids-induced TG accumulation. Additionally, adenovirus-mediated overexpression of KDM7A in mice resulted in hepatic steatosis, which was accompanied by increased expression of hepatic DGAT2. Furthermore, KDM7A overexpression decreased the enrichment of di-methylation of histone H3 lysine 9 (H3K9me2) and H3 lysine 27 (H3K27me2) on the promoter of DGAT2. Taken together, these results indicate that KDM7A overexpression induces hepatic steatosis through upregulation of DGAT2 by erasing H3K9me2 and H3K27me2 on the promoter.     

Targeted Induction of Endogenous VDUP1 by Small Activating RNA Inhibits the Growth of Lung Cancer Cells

Recent studies have reported that small double-strand RNAs (dsRNAs) can activate endogenous genes via an RNA-based promoter targeting mechanism termed RNA activation (RNAa). In the present study, we showed that dsVDUP1-834, a novel small activating RNA (saRNA) targeting promoter of vitamin D₃ up-regulated protein 1 (VDUP1) gene, up-regulated expression of VDUP1 at both mRNA and protein levels in A549 lung cancer cells. We also demonstrated that dsVDUP1-834 inhibited cell proliferation in A549 lung cancer cells. Further studies showed that dsVDUP1-834 induced cell-cycle arrest by increasing p27 and p53 and decreasing cyclin A and cyclin B1. In addition, knockdown of VDUP1 abrogated dsVDUP1-834-induced up-regulation of VDUP1 gene expression and related effects. The activation of VDUP1 by dsVDUP1-834 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 3 (H3ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) at the target site of VDUP1 promoter. Moreover, the enrichment of Ago2 was detected at the dsVDUP1-834 target site, and Ago2 knockdown significantly suppressed dsVDUP1-834-mediated inhibition of cell proliferation and modulation of cell-cycle regulators. Taken together, the results presented in this report demonstrate that dsVDUP1-834 induces VDUP1 gene expression by epigenetic changes, resulting in cell growth inhibition and cell-cycle arrest. Our results suggest that targeted induction of VDUP1 by dsVDUP1-834 might be a promising therapeutic strategy for the treatment of lung cancer.     

Comparative Analyses of Complete Chloroplast Genomes and Karyotypes of Allotetraploid Iris koreana and Its Putative Diploid Parental Species (Iris Series Chinenses,Iridaceae)

The Iris series Chinenses in Korea comprises four species (I. minutoaurea, I. odaesanensis, I. koreana, and I. rossii), and the group includes some endangered species, owing to their high ornamental, economic, and conservation values. Among them, the putative allotetraploid, Iris koreana (2n = 4x = 50), is hypothesized to have originated from the hybridization of the diploids I. minutoaurea (2n = 2x = 22) and I. odaesanensis (2n = 2x = 28) based on morphological characters, chromosome numbers, and genome size additivity. Despite extensive morphological and molecular phylogenetical studies on the genus Iris, little is known about Korean irises in terms of their complete chloroplast (cp) genomes and molecular cytogenetics that involve rDNA loci evolution based on fluorescence in situ hybridization (FISH). This study reports comparative analyses of the karyotypes of the three Iris species (I. koreana, I. odaesanensis, and I. minutoaurea), with an emphasis on the 5S and 35S rDNA loci number and localization using FISH together with the genome size and chromosome number. Moreover, the cp genomes of the same individuals were sequenced and assembled for comparative analysis. The rDNA loci numbers, which were localized consistently at the same position in all species, and the chromosome numbers and genome size values of tetraploid Iris koreana (four 5S and 35S loci; 2n = 50; 1C = 7.35 pg) were additively compared to its putative diploid progenitors, I. minutoaurea (two 5S and 35S loci; 2n = 22; 1C = 3.71 pg) and I. odaesanensis (two 5S and 35S loci; 2n = 28; 1C = 3.68 pg). The chloroplast genomes were 152,259–155,145 bp in length, and exhibited a conserved quadripartite structure. The Iris cp genomes were highly conserved and similar to other Iridaceae cp genomes. Nucleotide diversity analysis indicated that all three species had similar levels of genetic variation, but the cp genomes of I. koreana and I. minutoaurea were more similar to each other than to I. odaesanensis. Positive selection was inferred for psbK and ycf2 genes of the three Iris species. Phylogenetic analyses consistently recovered I. odaesanensis as a sister to a clade containing I. koreana and I. minutoaurea. Although the phylogenetic relationship, rDNA loci number, and localization, together with the genome size and chromosome number of the three species, allowed for the inference of I. minutoaurea as a putative maternal taxon and I. odaesanensis as a paternal taxon, further analyses involving species-specific molecular cytogenetic markers and genomic in situ hybridization are required to interpret the mechanisms involved in the origin of the chromosomal variation in Iris series Chinenses. This study contributes towards the genomic and chromosomal evolution of the genus Iris.     

Updates on the Role of Probiotics against Different Health Issues: Focus on Lactobacillus

This review article is built on the beneficial effects of Lactobacillus against different diseases, and a special focus has been made on its effects against neurological disorders, such as depression, multiple sclerosis, Alzheimer’s, and Parkinson’s disease. Probiotics are live microbes, which are found in fermented foods, beverages, and cultured milk and, when administered in an adequate dose, confer health benefits to the host. They are known as “health-friendly bacteria”, normally residing in the human gut and involved in maintaining homeostatic conditions. Imbalance in gut microbiota results in the pathophysiology of several diseases entailing the GIT tract, skin, immune system, inflammation, and gut–brain axis. Recently, the use of probiotics has gained tremendous interest, because of their profound effects on the management of these disease conditions. Recent findings suggest that probiotics enrichment in different human and mouse disease models showed promising beneficial effects and results in the amelioration of disease symptoms. Thus, this review focuses on the current probiotics-based products, different disease models, variable markers measured during trials, and evidence obtained from past studies on the use of probiotics in the prevention and treatment of different diseases, covering the skin to the central nervous system diseases.     

Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects

In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.     

Improved Synchronization Criteria for Chaotic Neural Networks with Sampled-data Control Subject to Actuator Saturation

International Journal of Control, Automation and Systems - In this paper, the synchronization problem for chaotic neural networks with sampled-data control and actuator saturation is investigated....     

Consumption of barley β‐glucan ameliorates fatty liver and insulin resistance in mice fed a high‐fat diet

Consumption of a diet high in barley β‐glucan (BG) has been shown to prevent insulin resistance. To investigate the mechanism for the effects of barley BG, three groups of male 7‐wk‐old C57BL/6J mice were fed high‐fat diets containing 0, 2, or 4% of barley BG for 12 wk. The 2% BG and 4% BG groups had significantly lower body weights compared with the 0% BG group. The 4% BG group demonstrated improved glucose tolerance and lower levels of insulin‐resistance index and glucose‐dependent insulinotropic polypeptide. Consumption of the BG diet decreased hepatic lipid content. Mice on the BG diet also demonstrated decreased fatty acid synthase and increased cholesterol 7α‐hydroxylase gene expression levels. The BG diet promoted hepatic insulin signaling by decreasing serine phosphorylation of insulin receptor substrate 1 and activating Akt, and it decreased mRNA levels of glucose‐6‐phosphatase and phosphoenolpyruvate carboxykinase. In summary, consumption of BG reduced weight gain, decreased hepatic lipid accumulation, and improved insulin sensitivity in mice fed a high‐fat diet. Insulin signaling enhanced due to the expression changes of glucose and lipid metabolism genes by BG consumption. Consumption of barley BG could be an effective strategy for preventing obesity, insulin resistance, and the metabolic syndrome.     

Megahertz operation of flexible low-voltage organic thin-film transistors

Bottom-gate, top-contact (inverted staggered) organic thin-film transistors with a channel length of 1 μm have been fabricated on flexible plastic substrates using the vacuum-deposited small-molecule semiconductor 2,9-didecyl-dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (C₁₀-DNTT). The transistors have an effective field-effect mobility of 1.2 cm²/V s, an on/off ratio of 10⁷, a width-normalized transconductance of 1.2 S/m (with a standard deviation of 6%), and a signal propagation delay (measured in 11-stage ring oscillators) of 420 ns per stage at a supply voltage of 3 V. To our knowledge, this is the first time that megahertz operation has been achieved in flexible organic transistors at supply voltages of less than 10 V.