Nephrotoxic Potential and Toxicokinetics of Melamine Combined with Cyanuric Acid in Rats

To investigate the nephrotoxic potential of melamine (MEL) and cyanuric acid (CA) in male Sprague-Dawley rats, 7-d repeated-dose studies were performed. The experimental groups of MEL100 and CA100 were orally administered with MEL and CA at 100 mg/kg/d for 7 d, respectively. In groups dosed with MEL–CA mixtures, melamine and cyanuric acid (1:1) were simultaneously administered at 4, 20, or 100 mg/kg/d for 7 d (i.e., MEL-CA4, MEL-CA20, or MEL-CA100, respectively). Body weights were not markedly affected in MEL100, CA100, and MEL-CA4 groups, but significantly reduced in MEL-CA 20 and 100 rats. Most parameters determined in sera and tissues were not markedly altered in MEL100, CA100, and MEL-CA4-treated rodents. However, BUN, creatinine, total protein, and kidney weights were significantly increased in MEL-CA20- and MEL-CA100-treated animals. Renal histopathologic findings also revealed signs of toxicity, including tubular dilatation, crystal deposition, granulomatous tubulo-interstitial inflammation, and tubular necrosis with regeneration. Data suggested that the combination of MEL and CA might be responsible for observed nephrotoxicity that was not seen following individual exposure to either MEL or CA alone. Subsequently, the concentrations of MEL and CA were determined in serum, urine, and kidney tissues by using liquid chromatography–mass spectrometry. Toxicokinetic studies indicated that MEL or CA alone might be eliminated almost completely within 24 h after dosing showing no accumulation in kidney. However, the combined MEL-CA dose produced marked accumulation of chemicals in blood and kidneys. These results suggested that combined MEL and CA might produce renal toxicity due to significant chemical accumulation in kidney accompanied by low excretion.     

Chitosan-Based Hybrid Nanocomplex for siRNA Delivery and Its Application for Cancer Therapy

Purpose

Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

Methods

Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.

Results

Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.

Conclusions

A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.     

High Electrochemical Performance Silicon Thin-Film Free-Standing Electrodes Based on Buckypaper for Flexible Lithium-Ion Batteries

Recently, applications for lithium-ion batteries (LIBs) have expanded to include electric vehicles and electric energy storage systems, extending beyond power sources for portable electronic devices. The power sources of these flexible electronic devices require the creation of thin, light, and flexible power supply devices such as flexile electrolytes/insulators, electrode materials, current collectors, and batteries that play an important role in packaging. Demand will require the progress of modern electrode materials with high capacity, rate capability, cycle stability, electrical conductivity, and mechanical flexibility for the time to come. The integration of high electrical conductivity and flexible buckypaper (oxidized Multi-walled carbon nanotubes (MWCNTs) film) and high theoretical capacity silicon materials are effective for obtaining superior high-energy-density and flexible electrode materials. Therefore, this study focuses on improving the high-capacity, capability-cycling stability of the thin-film Si buckypaper free-standing electrodes for lightweight and flexible energy-supply devices. First, buckypaper (oxidized MWCNTs) was prepared by assembling a free stand-alone electrode, and electrical conductivity tests confirmed that the buckypaper has sufficient electrical conductivity (10⁻⁴(S m⁻¹) in LIBs) to operate simultaneously with a current collector. Subsequently, silicon was deposited on the buckypaper via magnetron sputtering. Next, the thin-film Si buckypaper freestanding electrodes were heat-treated at 600 °C in a vacuum, which improved their electrochemical performance significantly. Electrochemical results demonstrated that the electrode capacity can be increased by 27/26 and 95/93 μAh in unheated and heated buckypaper current collectors, respectively. The measured discharge/charge capacities of the USi_HBP electrode were 108/106 μAh after 100 cycles, corresponding to a Coulombic efficiency of 98.1%, whereas the HSi_HBP electrode indicated a discharge/charge capacity of 193/192 μAh at the 100th cycle, corresponding to a capacity retention of 99.5%. In particular, the HSi_HBP electrode can decrease the capacity by less than 1.5% compared with the value of the first cycle after 100 cycles, demonstrating excellent electrochemical stability.     

Long-term Prognosis of Localized Lymphoid Hyperplasia of the Rectum

Background/AimsAlthough localized lymphoid hyperplasia (LLH) of the rectum is occasionally observed, its clinical implications are unclear. This study aimed to investigate the clinical course and significance of LLH of the rectum.MethodsWe identified 65 patients diagnosed with LLH of the rectum using a histopathologic examination and who received follow-up endoscopies between January 2009 and June 2015. Patients with a history of inflammatory bowel disease, lymphoma, familial adenomatous polyposis, or uncontrolled malignancy and patients who underwent scar biopsy after endoscopic resection or surgery were excluded. Endoscopic findings and clinical courses were analyzed.ResultsDuring the median follow-up of 31 months (interquartile range, 19 to 40 months), 81.5% (53/65) of LLHs of the rectum were resolved. Clinically significant diseases, including ulcerative colitis (UC, n=5) and mucosa-associated lymphoid tissue (MALT) lymphoma (n=1), were diagnosed in 9.2% of patients (6/65). The other six patients showed no significant changes in the lesion (n=3) or a waxing and waning appearance (n=3). According to endoscopic findings, all of the 47 polypoid types showed resolution or waxing and waning patterns. Five of the 11 nodular types (45.5%) developed into UC. One of the seven submucosal tumor (SMT)-like types (14.3%) developed into MALT lymphoma.ConclusionsLLH of the rectum with persistent symptoms or the endoscopic appearance of the nodular or SMT-like type may lead to clinically significant disease. Risk stratification according to endoscopic findings and careful surveillance are required for these lesions.     

Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated nuclear receptor expressed in all of the major cell types found in atherosclerotic lesions: monocytes/macrophages, endothelial cells, and smooth muscle cells. In vitro, PPARgamma ligands inhibit cell proliferation and migration, 2 processes critical for vascular lesion formation. In contrast to these putative antiatherogenic activities, PPARgamma has been shown in vitro to upregulate the CD36 scavenger receptor, which could promote foam cell formation. Thus, it is unclear what impact PPARgamma activation will have on the development and progression of atherosclerosis. This issue is important because thiazolidinediones, which are ligands for PPARgamma, have recently been approved for the treatment of type 2 diabetes, a state of accelerated atherosclerosis. We report herein that the PPARgamma ligand, troglitazone, inhibited lesion formation in male low density lipoprotein receptor-deficient mice fed either a high-fat diet, which also induces type 2 diabetes, or a high-fructose diet. Troglitazone decreased the accumulation of macrophages in intimal xanthomas, consistent with our in vitro observation that troglitazone and another thiazolidinedione, rosiglitazone, inhibited monocyte chemoattractant protein-1-directed transendothelial migration of monocytes. Although troglitazone had some beneficial effects on metabolic risk factors (in particular, a reduction of insulin levels in the diabetic model), none of the systemic cardiovascular risk factors was consistently improved in either model. These observations suggest that the inhibition of early atherosclerotic lesion formation by troglitazone may result, at least in part, from direct effects of PPARgamma activation in the artery wall.     

Independent association between glycated hemoglobin and arterial stiffness in healthy men

Aims/Introduction

Many studies have reported that high levels of glycated hemoglobin (HbA1c) are strongly associated with an increased risk of cardiovascular disease. Many researchers have not studied the association of HbA1c with various subclinical atherosclerosis phenotypes. We evaluated the impact of HbA1c on arterial stiffness and atherosclerosis in healthy Korean healthy men.

Materials and Methods

The study population included healthy adult men who participated in health check‐ups. All participants fasted for at least 8 h before taking the blood sample for fasting blood glucose, HbA1c, total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol and triglyceride. Arterial stiffness was measured using brachial‐ankle pulse wave velocity. Hierarchical regression analysis allowed us to determine the relationship between brachial‐ankle pulse wave velocity (baPWV) and potential risk factors for cardiovascular disease.

Results

Age and HbA1c were significantly related to baPWV, in model 1. In model 2, blood pressure was added to model 1. Systolic blood pressure was a more significant variable, which was more affected on baPWV than diastolic blood pressure. In the case of model 3, we included all variables regarding arterial stiffness. According to model 3, the most explainable variable was age, and then systolic blood pressure, body mass index and triglyceride, respectively.

Conclusions

We analyzed the associations between HbA1c, which is one of the risk factors, and arterial stiffness independently. An arterial stiffness measurement using baPWV can show the level of severity of the arteriosclerosis. When the level of stiffness has been increased, we could assume that the risk of arteriosclerosis would be increased. It can also be related to the increase of the risk of cardiovascular disease.     

Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome

Objective

Chronic pain frequently coexists with psychiatric symptoms in patients diagnosed with complex regional pain syndrome (CRPS). Previous studies have shown a relationship between CRPS and the risk of suicide. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS.

Methods

Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD), and symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I, SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI).

Results

Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p=0.002), severity of pain (p=0.024), and low scores on the GAF (p=0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep.

Conclusion

Significant risk factors for suicidal ideation in patients with CRPS include severity of pain, depressive symptoms, and decreased functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.     

Artificial selection for structural color on butterfly wings and comparison with natural evolution

Brilliant animal colors often are produced from light interacting with intricate nano-morphologies present in biological materials such as butterfly wing scales. Surveys across widely divergent butterfly species have identified multiple mechanisms of structural color production; however, little is known about how these colors evolved. Here, we examine how closely related species and populations of Bicyclus butterflies have evolved violet structural color from brown-pigmented ancestors with UV structural color. We used artificial selection on a laboratory model butterfly, B. anynana, to evolve violet scales from UV brown scales and compared the mechanism of violet color production with that of two other Bicyclus species, Bicyclus sambulos and Bicyclus medontias, which have evolved violet/blue scales independently via natural selection. The UV reflectance peak of B. anynana brown scales shifted to violet over six generations of artificial selection (i.e., in less than 1 y) as the result of an increase in the thickness of the lower lamina in ground scales. Similar scale structures and the same mechanism for producing violet/blue structural colors were found in the other Bicyclus species. This work shows that populations harbor large amounts of standing genetic variation that can lead to rapid evolution of scales’ structural color via slight modifications to the scales’ physical dimensions.Organisms produce colors in two basic ways: by synthesizing pigments that selectively absorb light of certain spectral bands so that only light outside the absorption bands is backscattered (chemical color) or by developing nanomorphologies that enhance the reflection of light of certain wavelengths by interference (physical color or structural color). Structural colors play major roles in natural and sexual selection in many species (1) and have a broad range of applications in color display, paint, cosmetics, and textile industries (2). Structural color surveys across widely divergent species have revealed a large diversity of color-producing mechanisms (3–9). However, there has been a lack of systematic study and comparison of how different colors from closely related species or within populations of a single species evolve, even though these colors can vary dramatically. By examining how these species/populations evolve different colors, it is possible to identify the minimal amount of morphological change that results in significant color variation. Furthermore, this research may serve as an inspiration for future application of similar evolutionary principles to the design of photonic devices for color tuning, light trapping, or beam steering (2, 10–20). From an evolutionary biology point of view, we are curious to examine how structural colors respond to selection pressure and whether there is sufficient standing genetic variation in natural populations to allow the rapid evolution of novel colors. Here we focus on determining the morphological changes and the physical mechanisms that cause the evolution of violet structural color in populations of a single species and also across different species within a single genus of butterflies.We focus on the genus Bicyclus (Lepidoptera: Nymphalidae), composed of more than 80 species that predominantly exhibit brown color along with marginal eyespots. Some Bicyclus species, however, have independently evolved transverse bands of bright violet/blue structural color on the dorsal surface of the forewings (black asterisks in Fig. 1A) (21, 22). One species, Bicyclus anynana, has become a model species amenable to laboratory rearing, and multiple aspects of its marginal eyespots (size, relative width of the color rings, shape) have been altered by artificial selection (23–27). However, change of color (hue), either pigmentary or structural, via artificial selection has not been reported. B. anynana does not exhibit bright violet coloration on its wings and therefore provides an excellent opportunity for investigating whether there is genetic potential to produce violet color upon directed selection. We investigated this potential by performing an artificial selection experiment in B. anynana that targeted the color of the specific dorsal wing region that evolved violet/blue coloration in other members of the genus (Fig. 1 B–G).Open in a separate windowFig. 1.Structural color in Bicyclus butterflies and basic wing scale morphology. (A) A phylogenetic estimate of Bicyclus butterfly relationships (modified from ref. 41) illustrating the evolution of color in the genus. The black asterisks mark two clades that evolved violet/blue color independently, represented here by B. sambulos and B. medontias. (B–D) Dorsal wing images of B. sambulos, B. anynana (the region used for artificial selection is marked by white asterisk), and B. medontias. (E–G) Graphs of reflectance spectra of the blue/violet wing band showing reflectance peaks in the 400–450 nm range and in the brown-colored homologous region in B. anynana with a UV reflectance peak centered at 300 nm (colored arrows). (H) 3D illustration of the wing and scales in the selected wing area of B. anynana. (I) Magnified view of the ripped region in H showing how cover (c; brown) and ground (g; green) scales are attached to the wing membrane (m, pink) and alternate along rows. Scales on the other (ventral) side of the wing membrane are visible also. (J) Cross-sectional view of a single scale showing the trabeculae (T) connecting the lower lamina (LL) to the upper lamina that includes ridges (R), microribs (Mr), and crossribs (Cr). Windows (W) are the spaces between the ridges and crossribs. Cover and ground scales have the same basic morphology. [llustrations in H–J courtesy of Katerina Evangelou (Central Saint Martin’s College, London).]B. anynana, like other butterflies, has two types of scales, cover and ground, which alternate within a row with cover scales partially covering the ground scales and the point where both scales attach to the wing membrane (Fig. 1 H and I and Fig. S1) (28). Both cover and ground scales contain a lower lamina with a continuous smooth surface below a region composed of longitudinal ridges and crossribs, collectively referred to as the “upper lamina” and connected to the lower lamina via pillars called “trabeculae” (Fig. 1J and Fig. S1) (6). Previous studies on butterflies showed that structural color can be produced by interference with light reflected from the overlapping lamella that build the longitudinal ridges, from microribs protruding from the sides of the longitudinal ridges, or from the lower lamina, which can vary in thickness and patterning (Fig. 1J) (29, 30). However, it is not clear how the violet/blue color is produced in members of the two Bicyclus clades that separately evolved this color, whether B. anynana can be made to evolve the same violet/blue color via artificial selection, and whether it will generate the color in the same way as the other species. To answer these questions, we conducted detailed optical characterization and structural analysis of butterfly wing scales from three separate species and artificially evolved populations of Bicyclus to illustrate how color is generated and how it has evolved.